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Sample records for allergen immunotherapy ait

  1. Allergen Immunotherapy (AIT): a prototype of Precision Medicine.

    PubMed

    Canonica, G W; Bachert, C; Hellings, P; Ryan, D; Valovirta, E; Wickman, M; De Beaumont, O; Bousquet, J

    2015-01-01

    Precision medicine is a medical model aiming to deliver customised healthcare - with medical decisions, practices, and/or products tailored to the individual patient informed but not directed by guidelines. Allergen immunotherapy has unique immunological rationale, since the approach is tailored to the specific IgE spectrum of an individual and modifies the natural course of the disease as it has a persistent efficacy after completion of treatment. In this perspective Allergen Immunotherapy - AIT has to be presently considered a prototype of Precision Medicine. Precise information and biomarkers provided by systems medicine and network medicine will address the discovery of Allergen immunotherapy biomarkers for (i) identification of the causes, (ii) stratification of eligible patients for AIT and (iii) the assessment of AIT efficacy. This area of medical technology is evolving rapidly and, compelemented by e-health, will change the way we practice medicine. It will help to monitor patients' disease control and data for (i) patient stratification, (ii) clinical trials, (iii) monitoring the efficacy and safety of targeted therapies which are critical for reaching an appropriate reimbursement. Biomarkers associated with e-health combined with a clinical decision support system (CDSS) will change the scope of Allergen immunotherapy. The cost/effectiveness of Allergen immunotherapy is a key issue for successful implementation. It should include the long-term benefits in the pharmaco-economic evaluation, since no other allergy treatment has this specific characteristic. AIT is the prototype of current and future precision medicine. PMID:26594303

  2. Allergen Immunotherapy.

    PubMed

    Rael, Efren

    2016-09-01

    Allergies affect a large proportion of the population. Allergies can adversely affect productivity, sleep, and quality of life and can lead to life-threatening reactions. Allergies can spread to affect multiple organ systems. Allergen immunotherapy is the only therapy that can change the natural history of allergic disease. PMID:27545737

  3. Allergen immunotherapy in polysensitized patient.

    PubMed

    Hrubiško, M; Špičák, V

    2016-05-01

    Specific allergen immunotherapy (AIT) is the only therapeutic method with positive impact on natural course of allergic disease - affecting clinical development (including the progression of rhinitis to asthma) and new sensitisations. The actual problem is the increasing number of patients manifesting poly-sensitivity in allergy skin tests and / or in specific IgE tests. Usually, AIT is not recommended in such individuals. The objective we are facing is that in many patients tested as poly-reactive, we have to distinguish in which cases it is a true polysensitization, and when it is due to cross-reactivity of specific IgE antibodies induced by panallergens. This may really determine when AIT may be an appropriate course of action. The article focuses on this problem in more detail, applying the long time Czech and Slovak experience with allergy testing and allergen immunotherapy. PMID:27152601

  4. Allergen Immunotherapy: Past, Present, and Future

    PubMed Central

    Kosowska, Anna; Smolinska, Sylwia

    2016-01-01

    Allergen-specific immunotherapy (AIT), although in clinical use for more than a century, is still the only causal treatment of allergic diseases. The safety and efficacy of AIT has been demonstrated in a large number of clinical trials. In addition to allergy symptom reduction AIT plays an essential role in preventing new allergies and asthma and shows long-term effects after discontinuation of treatment. Ideally, it is capable of curing allergy. However, AIT is not effective in all allergic individuals and is not equally effective in the treatment of various hypersensitivities to different allergens. For many years, the route of administration and the vaccine compositions have been evolving. Still there is a strong need for research in the field of new AIT modalities to increase its effectiveness and safety. Growing evidence on immunological effects of AIT, especially new T cell subsets involved in antigen/allergen tolerance, provides novel concepts for safer and more effective vaccination. Pharmacoeconomic studies have demonstrated a clear advantage of AIT over pharmacologic therapies. PMID:26922928

  5. Allergen Immunotherapy: Past, Present, and Future.

    PubMed

    Jutel, Marek; Kosowska, Anna; Smolinska, Sylwia

    2016-05-01

    Allergen-specific immunotherapy (AIT), although in clinical use for more than a century, is still the only causal treatment of allergic diseases. The safety and efficacy of AIT has been demonstrated in a large number of clinical trials. In addition to allergy symptom reduction AIT plays an essential role in preventing new allergies and asthma and shows long-term effects after discontinuation of treatment. Ideally, it is capable of curing allergy. However, AIT is not effective in all allergic individuals and is not equally effective in the treatment of various hypersensitivities to different allergens. For many years, the route of administration and the vaccine compositions have been evolving. Still there is a strong need for research in the field of new AIT modalities to increase its effectiveness and safety. Growing evidence on immunological effects of AIT, especially new T cell subsets involved in antigen/allergen tolerance, provides novel concepts for safer and more effective vaccination. Pharmacoeconomic studies have demonstrated a clear advantage of AIT over pharmacologic therapies. PMID:26922928

  6. Allergen extracts for immunotherapy: to mix or not to mix?

    PubMed

    Nony, Emmanuel; Martelet, Armelle; Jain, Karine; Moingeon, Philippe

    2016-03-01

    Allergen immunotherapy (AIT) is established as a curative treatment for allergic rhinitis, asthma, as well as insect venom allergy. AIT is based on the administration of natural allergen extracts via the subcutaneous or sublingual routes to reorient the immune system towards tolerogenic mechanisms. In this regard, since many patients are poly-allergic, mixtures of allergen extracts are often used with a potential risk to cause allergen degradation, thereby affecting treatment efficacy. Herein, we discuss the advantages and drawbacks of mixing homologous (i.e., related) or heterogeneous (i.e., unrelated) allergen extracts. We provide evidence for incompatibilities between mixes of grass pollen and house dust mite extracts containing bodies and feces, and summarize critical points to consider when mixing allergen extracts for AIT. PMID:26652799

  7. International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics.

    PubMed

    Jutel, Marek; Agache, Ioana; Bonini, Sergio; Burks, A Wesley; Calderon, Moises; Canonica, Walter; Cox, Linda; Demoly, Pascal; Frew, Antony J; O'Hehir, Robyn; Kleine-Tebbe, Jörg; Muraro, Antonella; Lack, Gideon; Larenas, Désirée; Levin, Michael; Martin, Bryan L; Nelson, Harald; Pawankar, Ruby; Pfaar, Oliver; van Ree, Ronald; Sampson, Hugh; Sublett, James L; Sugita, Kazunari; Du Toit, George; Werfel, Thomas; Gerth van Wijk, Roy; Zhang, Luo; Akdis, Mübeccel; Akdis, Cezmi A

    2016-02-01

    This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein. PMID:26853128

  8. Clinical contraindications to allergen immunotherapy: an EAACI position paper.

    PubMed

    Pitsios, C; Demoly, P; Bilò, M B; Gerth van Wijk, R; Pfaar, O; Sturm, G J; Rodriguez del Rio, P; Tsoumani, M; Gawlik, R; Paraskevopoulos, G; Ruëff, F; Valovirta, E; Papadopoulos, N G; Calderón, M A

    2015-08-01

    Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient. PMID:25913519

  9. Allergen-specific immunotherapy in pediatric allergic asthma

    PubMed Central

    2016-01-01

    Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma. PMID:27489785

  10. Allergen-specific immunotherapy in pediatric allergic asthma.

    PubMed

    Yukselen, Ayfer

    2016-07-01

    Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma. PMID:27489785

  11. New strategies for allergen immunotherapy.

    PubMed

    Carnés, Jerónimo; Robinson, Douglas S

    2008-06-01

    Specific allergen immunotherapy, consisting in the administration of increasing amounts of offending allergens into sensitive patients was first used nearly one hundred years ago and remains in use worldwide for treatment of allergic rhinitis and asthma. It has been recognised as the only effective treatment for type I allergic diseases when the appropriate quantities of allergens are used. The immunological mechanisms by which specific immunotherapy is effective include the modulation of T cells and the response of B-cells and is accompanied by significant decreases of specific IgE and increases in allergen specific IgG antibodies, mainly IgG4. While specific allergen injection immunotherapy is highly effective and the most common way of administration other routes such as oral or intranasal ways have been considered as and alternative to subcutaneous injections. During the last century, allergenic vaccines have been prepared using individual allergens adsorbed to different adjuvant substances. These vaccines have demonstrated efficacy and good results in different clinical trials. However, many novel approaches to allergen immunotherapy have been developed in the last years in order to increase the safety and efficacy of allergenic vaccines. In that way, different and modern vaccines have been prepared including more purified products such as depigmented allergen extracts; allergoids, consisting on big molecules of thousands of kDa, which contain all the individual allergens and show a significant decrease in severe adverse reactions; peptides or small aminoacid sequences; recombinant allergens; hypoallergenic vaccines where the IgE binding sites have been modified; or allergen-CpG fusion molecules. New presentations are under study and new treatments will be developed in the near future with the objective that the prevention of allergic disease may become a reality. The review article also discuss recent patent related to the field. PMID:19075996

  12. Mechanisms of subcutaneous allergen immunotherapy.

    PubMed

    Soyer, Ozge U; Akdis, Mubeccel; Akdis, Cezmi A

    2011-05-01

    Allergen-specific immunotherapy (SIT) is the only curative approach in the treatment of allergic diseases defined up-to-date. Peripheral T-cell tolerance to allergens, the goal of successful allergen-SIT, is the primary mechanism in healthy immune responses to allergens. By repeated administration of increased doses of the causative allergen, allergen-SIT induces a state of immune tolerance to allergens through the constitution of T regulatory (Treg) cells, including allergen-specific interleukin (IL)-10-secreting Treg type 1 cells and CD4(+)CD25(+)Treg cells; induction of suppressive cytokines, such as IL-10 and transforming growth factor β; suppression of allergen-specific IgE and induction of IgG4 and IgA; and suppression of mast cells, basophils, eosinophils, and inflammatory dendritic cells. This review summarizes the current knowledge on the mechanisms of allergen-SIT with emphasis on the roles of Treg cells in allergen-SIT. PMID:21530813

  13. Recombinant allergens for specific immunotherapy.

    PubMed

    Cromwell, Oliver; Häfner, Dietrich; Nandy, Andreas

    2011-04-01

    Recombinant DNA technology provides the means for producing allergens that are equivalent to their natural counterparts and also genetically engineered variants with reduced IgE-binding activity. The proteins are produced as chemically defined molecules with consistent structural and immunologic properties. Several hundred allergens have been cloned and expressed as recombinant proteins, and these provide the means for making a very detailed diagnosis of a patient's sensitization profile. Clinical development programs are now in progress to assess the suitability of recombinant allergens for both subcutaneous and sublingual immunotherapy. Recombinant hypoallergenic variants, which are developed with the aim of increasing the doses that can be administered while at the same time reducing the risks for therapy-associated side effects, are also in clinical trials for subcutaneous immunotherapy. Grass and birch pollen preparations have been shown to be clinically effective, and studies with various other allergens are in progress. Personalized or patient-tailored immunotherapy is still a very distant prospect, but the first recombinant products based on single allergens or defined mixtures could reach the market within the next 5 years. PMID:21377719

  14. Recent progress in allergen immunotherapy.

    PubMed

    Nouri-Aria, Kayhan T

    2008-03-01

    The efficacy of allergen immunotherapy for the treatment of allergic rhinoconjunctivitis with or without seasonal bronchial asthma and anaphylaxis caused by the sting of the hymenoptera class of insects has been clearly demonstrated in numerous well-designed, placebo-controlled trials. Immunotherapy whether by subcutaneous injection of allergen extract or by oral/sublingual routes modifies peripheral and mucosal TH2 responses in favour of TH1 responses and augments IL-10 synthesis by TRegs both locally and by peripheral T cells. Recent researches into the cellular and molecular basis of allergic reactions have advanced our understanding of the mechanisms involved in allergic diseases. They have also helped the development of innovative approaches that are likely to further improve the control of allergic responses in the future. Novel approaches to immunotherapy that are currently being explored include the use of peptide-based allergen preparations, which do not bind IgE and therefore do not activate mast cells, but reduce both Th1 and Th2-cytokine synthesis, while increasing levels of IL-10. Alternative strategies include the use of adjuvants, such as nucleotide immunostimulatory sequences derived from bacteria CpG or monophosphoryl lipid A that potentiate Th1 responses. Blocking the effects of IgE using anti-IgE such as omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE, has been shown to be a useful strategy in the treatment of allergic asthma and rhinitis. The combination of anti-IgE-monoclonal antibody omalizumab with allergen immunotherapy has proved beneficial for the treatment of allergic diseases, offering improved efficacy, limited adverse effects, and potential immune-modifying effects. This combination may also accelerate the rapidity by which immunotherapy induces TReg cells. If allergic diseases are due to a lack of allergen-specific TReg cells, then effective therapies should target the induction and the

  15. Allergen immunotherapy: how to balance the different views from pulmonologists and allergists?

    PubMed

    Incorvaia, Cristoforo; Fuiano, Nicola; Frati, Franco

    2012-08-01

    Allergen immunotherapy (AIT) is the treatment characterizing the allergological approach to respiratory allergy. Unfortunately, most available data from the literature and current practice indicate that pulmonologists do no consider AIT when choosing the treatment strategy in patients with asthma. Indeed AIT, from its introduction in 1911 to nowadays, was unceasingly improved and has accumulated clear evidence on its effectiveness. Moreover, AIT has a characteristic not shared by drugs in the capacity to modify the natural history of asthma, due to its immunologic mechanisms of actions, and thus also works after the treatment withdrawal. This also makes AIT a clearly cost-effective treatment over time. It is surprising that pulmonologists, for whom asthma is a major disease to manage, do not consider AIT when choosing the optimal treatment in single patients. The insufficient information on AIT and the availability of allergen extracts with less than good quality are likely to be the most important factors influencing such an attitude. The current development of standardized, pharmaceutical-grade products for AIT seems capable of making allergen extracts comparable to drugs and to stimulate a rethinking of AIT's role in the treatment of asthma in pulmonologists. A reappraisal of the significance of the allergen-specific bronchial challenge could represent a further factor suggesting AIT as a reliable option. PMID:22947011

  16. Preventive capacity of allergen immunotherapy on the natural history of allergy.

    PubMed

    Incorvaia, C

    2013-06-01

    Allergen immunotherapy (AIT) is the practice of administering gradually increasing doses of the specific causative allergen to reduce the clinical reactivity of allergic subjects. A bulk of literature demonstrates that AIT is an effective and safe treatment to reduce allergic symptoms and the use of drugs. The preventive capacity of AIT is less investigated. The studies thus far available showed that this treatment, in both forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) is able to prevent the development of asthma in patients with allergic rhinitis and the occurrence of new sensitizations in patients monosensitized. Such outcomes demonstrate the ability of AIT to change the natural history of respiratory allergy. Of particular importance, SCIT with Hymenoptera venom has an invaluable role in preventing potentially fatal anaphylactic reactions to the culprit sting in venom-allergic patients. Ongoing studies are aimed at evaluating the possible capacity of AIT in primary prevention of allergy. All these capabilities are related to the mechanisms of action of AIT. In fact, both SCIT and SLIT are able to modify the allergen presentation by dendritic cells that in turn modify the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation, to a Th1-type response. An important role is played by allergen-specific T regulatory (Treg) cells, which produce suppressive cytokines such as IL-10 and TGF-beta. PMID:24396984

  17. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens.

    PubMed

    Akdis, Cezmi A; Akdis, Mübeccel

    2015-01-01

    Substantial progress in understanding mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumors, organ transplantation and chronic infections has led to a variety of targeted therapeutic approaches. Allergen-specific immunotherapy (AIT) has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific way of treatment. The mechanisms by which allergen-AIT has its mechanisms of action include the very early desensitization effects, modulation of T- and B-cell responses and related antibody isotypes as well as inhibition of migration of eosinophils, basophils and mast cells to tissues and release of their mediators. Regulatory T cells (Treg) have been identified as key regulators of immunological processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in AIT. Naturally occurring FoxP3(+) CD4(+)CD25(+) Treg cells and inducible type 1 Treg (Tr1) cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector Th1, Th2 and Th17 cells; suppression of allergen-specific IgE, and induction of IgG4; suppression of mast cells, basophils and eosinophils and suppression of effector T cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and regulatory T cell subsets. PMID:26023323

  18. New routes for allergen immunotherapy.

    PubMed

    Johansen, Pål; von Moos, Seraina; Mohanan, Deepa; Kündig, Thomas M; Senti, Gabriela

    2012-10-01

    IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long lasting protective effects and can stop the progression of the disease. However, few allergic patients choose to undergo SIT, due to the long treatment time and potential allergic adverse events. Since the beneficial effects of SIT are mediated by antigen presenting cells inducing Th1, Treg and antibody responses, whereas the adverse events are caused by mast cells and basophils, the therapeutic window of SIT may be widened by targeting tissues rich in antigen presenting cells. Lymph nodes and the epidermis contain high density of dendritic cells and low numbers of mast cells and basophils. The epidermis has the added benefit of not being vascularised thereby reducing the chances of anaphylactic shock due to leakage of allergen. Hence, both these tissues represent highly promising routes for SIT and are the focus of discussion in this review. PMID:23095873

  19. Mechanisms of allergen-specific immunotherapy.

    PubMed

    Akdis, Cezmi A; Akdis, Mübeccel

    2011-01-01

    Allergen-specific immunotherapy has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific method of treatment. The mechanisms of action of allergen-specific immunotherapy include the very early desensitization effects, modulation of T-and B-cell responses and related antibody isotypes, and migration of eosinophils, basophils, and mast cells to tissues, as well as release of their mediators. Regulatory T (Treg) cells have been identified as key regulators of immunologic processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in patients undergoing allergen-specific immunotherapy. Naturally occurring forkhead box protein 3-positive CD4(+)CD25(+) Treg cells and inducible T(R)1 cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector T(H)1, T(H)2, and T(H)17 cells; suppression of allergen-specific IgE and induction of IgG4; suppression of mast cells, basophils, and eosinophils; and suppression of effector T-cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and Treg cell subsets. PMID:21211639

  20. Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future

    PubMed Central

    Valenta, Rudolf; Campana, Raffaela; Focke-Tejkl, Margit; Niederberger, Verena

    2016-01-01

    In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination. PMID:26853127

  1. Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future.

    PubMed

    Valenta, Rudolf; Campana, Raffaela; Focke-Tejkl, Margit; Niederberger, Verena

    2016-02-01

    In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination. PMID:26853127

  2. Mechanisms of allergen-specific immunotherapy.

    PubMed

    Akdis, Mübeccel; Akdis, Cezmi A

    2007-04-01

    Allergen-specific immunotherapy (SIT) has been used for almost a century as a desensitizing therapy for allergic diseases and represents the only curative and specific method of treatment. Administration of appropriate concentrations of allergen extracts has been shown to be reproducibly effective when patients are carefully selected. The mechanisms by which allergen-SIT has its effects include the modulation of T-cell and B-cell responses and related antibody isotypes as well as effector cells of allergic inflammation, such as eosinophils, basophils, and mast cells. The balance between allergen-specific T-regulatory (Treg) and T(H)2 cells appears to be decisive in the development of allergic and healthy immune responses against allergens. Treg cells consistently represent the dominant subset specific for common environmental allergens in sensitized healthy individuals. In contrast, there is a high frequency of allergen-specific T(H)2 cells in patients with allergy. The induction of a tolerant state in peripheral T cells represents an essential step in allergen-SIT. Peripheral T-cell tolerance is characterized mainly by generation of allergen-specific Treg cells leading to suppressed T-cell proliferation and T(H)1 and T(H)2 cytokine responses against the allergen. This is accompanied by a significant increase in allergen-specific IgG(4), and also IgG(1) and IgA, and a decrease in IgE in the late stage of the disease. In addition, decreased tissue infiltration of mast cells and eosinophils and their mediator release including circulating basophils takes place. Current understanding of mechanisms of allergen-SIT, particularly the role of Treg cells in peripheral tolerance, may enable novel treatment strategies. PMID:17321578

  3. Immunological mechanisms of allergen-specific immunotherapy.

    PubMed

    Jutel, Marek; Akdis, C A

    2011-06-01

    The studies on the mechanisms of specific immunotherapy (SIT) point out its targets that decide on the efficacy of SIT and hence might be used for its further improvement. Several mechanisms have been proposed to explain the beneficial effects of immunotherapy. The knowledge of the mechanisms underlying allergic diseases and curative treatment possibilities has experienced exciting advances over the last three decades. Studies in several clinical trials in allergen-SIT have demonstrated that the induction of a tolerant state against allergens in many ways represents a key step in the development of a healthy immune response against allergens. Several cellular and molecular mechanisms have been demonstrated: allergen-specific suppressive capacities of both inducible subsets of CD4(+) CD25(+) forkhead box P3(+) T-regulatory and IL-10-secreting type 1 T-regulatory cells increase in peripheral blood; suppression of eosinophils, mast cells, and basophils; Ab isotype change from IgE to IgG4. This review aims at the better understanding of the observed immunological changes associated with allergen SIT. PMID:21466562

  4. Mechanisms of allergen-specific immunotherapy.

    PubMed

    Fujita, Hiroyuki; Soyka, Michael B; Akdis, Mübeccel; Akdis, Cezmi A

    2012-01-01

    Allergen-specific immunotherapy (allergen-SIT) is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg) cells and inducible IL-10- and TGF-β-producing type 1 Treg (Tr1) cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro-inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non-inflammatory antibodies particularly IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases. PMID:22409879

  5. C-type Lectin Receptor Expression on Human Basophils and Effects of Allergen-Specific Immunotherapy.

    PubMed

    Lundberg, K; Rydnert, F; Broos, S; Andersson, M; Greiff, L; Lindstedt, M

    2016-09-01

    Basophils are emerging as immunoregulatory cells capable of interacting with their environment not only via their characteristic IgE-mediated activation, but also in an IgE-independent manner. Basophils are known to express and respond to stimulation via TLR2, TLR4, DC-SIGN and DCIR, but whether basophils also express other C-type lectin receptors (CLRs) is largely unknown. In this study, we investigate the CLR expression profile of human basophils using multicolour flow cytometry. As FcRs as well as some CLRs are associated with allergen recognition and shown to be involved in subsequent immune responses, the expression of CLRs and FcRs on peripheral blood basophils, as well as their frequency, was monitored for 1 year in subjects undergoing subcutaneous allergen-specific immunotherapy (AIT). Here, we show that human basophils express CLECSF14, DEC205, Dectin-1, Dectin-2 and MRC2. Furthermore, we demonstrate that the frequencies of basophils expressing the allergy-associated CLRs Dectin-1 and Dectin-2 were significantly reduced after 1 year and 8 weeks of AIT, respectively. In contrast, the frequency of basophils positive for FcγRII, as well as the fraction of total basophils, significantly increased after 1 year of AIT. The herein demonstrated expression of various CLRs on basophils, and their altered CLR and FcR expression profile upon AIT, suggest yet unexplored ways by which basophils can interact with antigens and may point to novel immunoregulatory functions targeted through AIT. PMID:27354239

  6. Allergen immunotherapy for birch pollen-allergic patients: recent advances.

    PubMed

    Moingeon, Philippe; Floch, Véronique Bordas-Le; Airouche, Sabi; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent

    2016-05-01

    As of today, allergen immunotherapy is performed with aqueous natural allergen extracts. Recombinant allergen vaccines are not yet commercially available, although they could provide patients with well-defined and highly consistent drug substances. As Bet v 1 is the major allergen involved in birch pollen allergy, with more than 95% of patients sensitized to this allergen, pharmaceutical-grade recombinant Bet v 1-based vaccines were produced and clinically tested. Herein, we compare the clinical results and modes of action of treatments based on either a birch pollen extract or recombinant Bet v 1 expressed as hypoallergenic or natural-like molecules. We also discuss the future of allergen immunotherapy with improved drugs intended for birch pollen-allergic patients suffering from rhinoconjunctivitis. PMID:27140409

  7. Chapter 3: Allergen immunotherapy: definition, indication, and reactions.

    PubMed

    Georgy, Mary S; Saltoun, Carol A

    2012-01-01

    Specific allergen immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. It is a disease modifying therapy, indicated for the treatment of allergic rhinitis, allergic asthma, and hymenoptera hypersensitivity. Specific IgE antibodies for appropriate allergens for immunotherapy must be documented. Indications for allergen immunotherapy include (1) inadequate symptom control despite pharmacotherapy and avoidance measures, (2) a desire to reduce the morbidity from allergic rhinitis and/or asthma or reduce the risk of anaphylaxis from a future insect sting, (3) when the patient experiences undesirable side effects from pharmacotherapy, and (4) when avoidance is not possible. Furthermore, patients may seek to benefit from economic savings of allergen immunotherapy compared with pharmacotherapy over time. Several studies have reported that immunotherapy in children with allergic rhinitis appears to prevent the development of new allergic sensitizations and/or new-onset asthma. Humoral, cellular, and tissue level changes occur with allergen immunotherapy including large increases in antiallergen IgG(4) antibodies, a decrease in the postseasonal rise of antiallergen IgE antibodies, reduced numbers of nasal mucosal mast cells and eosinophils, induction of Treg cells, and suppression of Th2 more than Th1 lymphocytes. There is a corresponding increase in IL-10 and transforming growth factor beta. In the United States, allergen immunotherapy is administered by the subcutaneous route in the physician's office, whereas primarily in some countries in Europe, it is administered for allergic rhinitis and asthma by the sublingual route by the patient at home. PMID:22794676

  8. Allergen immunotherapy: routes, safety, efficacy, and mode of action

    PubMed Central

    Hochfelder, Jillian Leigh; Ponda, Punita

    2013-01-01

    Allergic rhinitis, allergic conjunctivitis, and allergic asthma have been steadily increasing in prevalence in recent years. These allergic diseases have a major impact on quality of life and are a major economic burden in the US. Although allergen avoidance and pharmacotherapy are currently the mainstays of therapy, they are not always successful in treating patients’ symptoms effectively. If a patient fails allergen avoidance and medical therapy, immunotherapy may be indicated. Furthermore, immunotherapy is the only therapy that may change the course of the disease and induce long-term remission. Though subcutaneous administration has been the standard route for immunotherapy for many decades, there are several other routes of administration that have been and are currently being studied. The goal of utilizing alternative routes of immunotherapy is to improve safety without decreasing the efficacy of treatment. This paper will review the novel routes of immunotherapy, including sublingual, oral, local nasal, epicutaneous, and intralymphatic.

  9. Safety of engineered allergen-specific immunotherapy vaccines

    PubMed Central

    Focke-Tejkl, Margarete; Valenta, Rudolf

    2015-01-01

    Purpose of review The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines. Recent findings In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule. Summary Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines. PMID:22885888

  10. Allergen-specific immunotherapy: from therapeutic vaccines to prophylactic approaches

    PubMed Central

    Valenta, R.; Campana, R.; Marth, K.; van Hage, M.

    2015-01-01

    Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only disease-modifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease. PMID:22640224

  11. Review on immunotherapy in airway allergen sensitised patients.

    PubMed

    van der Valk, J P M; de Jong, N W; Gerth van Wijk, R

    2015-07-01

    Allergen immunotherapy is a more than 100-year-old treatment in particular for birch pollen, grass pollen, house dust mite and cat dander sensitised allergic patients. The mechanism of allergen-specific immunotherapy is complex. Different hypotheses have been postulated to explain the mode of action, such as a decrease of the number of tissue mast cells, eosinophils and basophils, an increase of IgG4 and IgA synthesis, a shift from Th2 to Th1 cells and an increase in the number and function of IL-10 producing T-regulatory cells (T-reg). All these immunological effects may contribute to immune tolerance and long-term changes in the immune system. The efficacy and safety of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) with pollen and house dust mite have been investigated in many trials, meta-analyses and reviews. Nowadays grass pollen SLIT and SCIT, and birch pollen and house dust mite SCIT are implemented in clinical practice to treat therapy-resistant patients. However, the treatment is not effective for all patients and often not without side effects. Therefore, the development of new, safer and more effective immunotherapies is needed. These are approached along novel routes, including improved administration, combined treatment with immune response modifiers, fusion with immune response modifiers, allergen coupled to adjuvants and reconstruction of natural extracts with multiple recombinant allergens or with modified allergens. These developments are promising, but more research is required to implement them in clinical practice. PMID:26228190

  12. Allergen-Specific Immunotherapy Alters the Frequency, as well as the FcR and CLR Expression Profiles of Human Dendritic Cell Subsets

    PubMed Central

    Lundberg, Kristina; Rydnert, Frida; Broos, Sissela; Andersson, Morgan; Greiff, Lennart; Lindstedt, Malin

    2016-01-01

    Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcεRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance. PMID:26863539

  13. EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.

    PubMed

    Calderon, Moises A; Demoly, Pascal; Gerth van Wijk, Roy; Bousquet, Jean; Sheikh, Aziz; Frew, Anthony; Scadding, Glenis; Bachert, Claus; Malling, Hans J; Valenta, Rudolph; Bilo, Beatrice; Nieto, Antonio; Akdis, Cezmi; Just, Jocelyne; Vidal, Carmen; Varga, Eva M; Alvarez-Cuesta, Emilio; Bohle, Barbara; Bufe, Albrecht; Canonica, Walter G; Cardona, Victoria; Dahl, Ronald; Didier, Alain; Durham, Stephen R; Eng, Peter; Fernandez-Rivas, Montserrat; Jacobsen, Lars; Jutel, Marek; Kleine-Tebbe, Jörg; Klimek, Ludger; Lötvall, Jan; Moreno, Carmen; Mosges, Ralph; Muraro, Antonella; Niggemann, Bodo; Pajno, Giovanni; Passalacqua, Giovanni; Pfaar, Oliver; Rak, Sabina; Senna, Gianenrico; Senti, Gabriela; Valovirta, Erkka; van Hage, Marianne; Virchow, Johannes C; Wahn, Ulrich; Papadopoulos, Nikolaos

    2012-01-01

    Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a

  14. A review of allergy and allergen specific immunotherapy.

    PubMed

    Bidad, Katayoon; Nicknam, Mohammad Hossein; Farid, Reza

    2011-03-01

    Since 20th century, when allergy was defined, an ongoing attempt for discovering the mechanisms underlying it and its treatment began. Defining allergens as well as cells such as regulatory T-cells and characterizing the antibodies involved in the pathogenesis (including blocking antibodies) have helped very much towards a better understanding of the immunologic process. However, allergen specific immunotherapy (SIT), as a specific curative treatment for allergy also dates back to the beginning of the previous century and has progressed considerably during these years. SIT similar to natural immunomodulation, directs the immune response towards tolerance. New strategies in this field, such as using recombinant allergens, T- and B-cell-epitope-containing peptides, and DNA vaccination have shown promising results. Sublingual immunotherapy, although not yet FDA-approved, as an alternative strategy in SIT has demonstrated efficacy as well as safety. Furthermore, allergen extracts, their standardization and their modification have also been the focus of much research. Undoubtedly, specific immunotherapy is proven to be an efficacious method to treat allergy, so its cost-effectiveness should be estimated in developing countries in order to include it in the country's health priorities. Informing physicians about the new anti-vaccination movement is also crucial. PMID:21358009

  15. Sublingual allergen immunotherapy in HIV-positive patients.

    PubMed

    Iemoli, E; Borgonovo, L; Fusi, A; Magni, C; Ricci, E D; Rizzardini, G; Piconi, S

    2016-03-01

    HIV infection is a relative contraindication for allergic immunotherapy (AIT). In the last decade, highly active antiretroviral therapy (HAART) has improved the immune function and life expectancy in HIV-infected patients whose respiratory allergic incidence is similar to the general population. We evaluated the safety and clinical effectiveness of sublingual immunotherapy in a group of grass pollen-allergic HAART-treated HIV-positive patients. Thirteen patients received sublingual immunotherapy (SLIT) tablet (Oralair, Stallergenes©) and symptomatic therapy and were compared with nine patients receiving symptomatic therapy alone. Clinical benefits were evaluated by the analysis of total combined score (TCS), sum of symptom-medication score, and a quality of life (QoL) questionnaire. HIV viral load and peripheral TCD4 lymphocytes were analyzed at the beginning and at the end of the study. Clinical efficacy data showed a significant improvement in SLIT-treated patients compared to controls (TCS: P = 0.0001; QoL: P = 0.03). We did not observe any significant alteration of TCD4 cell counts and viral load (VL) in both groups. Our preliminary data showed that SLIT therapy in viro-immunological controlled HAART treated HIV positive patients was efficacious, safe and well tolerated. PMID:26228482

  16. Longitudinal profiles of serum specific IgE and IgG4 to Dermatophagoides pteronyssinus allergen and its major components during allergen immunotherapy in a cohort of southern Chinese children.

    PubMed

    Zeng, Guangqiao; Zheng, Peiyan; Luo, Wenting; Huang, Huimin; Wei, Nili; Sun, Baoqing

    2016-06-01

    Longitudinal data on serum specific sIgE and sIgG4 to allergen component of Dermatophagoides pteronyssinus (Der p) during allergen immunotherapy (AIT) are limited in Chinese populations. We serially followed up serum sIgE and sIgG4 to Der p and its components (Der p 1 and 2) in 51 Der p-sensitized children receiving guideline-based medications alone and additional 36-month AIT. The the Der p 1 and Der p 2 sIgE levels were elevated at 6 months and progressively declined from 12 months; the sIgG4 levels for Der p, Der p 1 and Der p 2 were increasing during the first year and reached a plateau thereafter; the sIgE/sIgG4 ratios for Der p 1 and Der p 2 decreased continuously from 6 through 24 months of AIT. Subgroup analysis showed that younger children (≤8years) experienced a greater increase in sIgG4 levels for Der p, Der p 1 and Der p 2 during AIT compared with older children (9-16 years). In summary, sIgE and sIgG4 to Der p 1 and Der p 2 may be more useful than those to Der p in reflecting the change in immunological reactivity during AIT. Earlier delivery of AIT may yield greater increase in sIgG4 after 36-month treatment than given later in life. PMID:27111568

  17. Allergen hybrids – next generation vaccines for Fagales pollen immunotherapy

    PubMed Central

    Pichler, U; Hauser, M; Hofer, H; Himly, M; Hoflehner, E; Steiner, M; Mutschlechner, S; Hufnagl, K; Ebner, C; Mari, A; Briza, P; Bohle, B; Wiedermann, U; Ferreira, F; Wallner, M

    2013-01-01

    Summary Background Trees belonging to the order of Fagales show a distinct geographical distribution. While alder and birch are endemic in the temperate zones of the Northern Hemisphere, hazel, hornbeam and oak prefer a warmer climate. However, specific immunotherapy of Fagales pollen-allergic patients is mainly performed using birch pollen extracts, thus limiting the success of this intervention in birch-free areas. Objectives T cells are considered key players in the modification of an allergic immune response during specific immunotherapy (SIT), therefore we thought to combine linear T cell epitope-containing stretches of the five most important Fagales allergens from birch, hazel, alder, oak and hornbeam resulting in a Fagales pollen hybrid (FPH) molecule applicable for SIT. Methods A Fagales pollen hybrid was generated by PCR-based recombination of low IgE-binding allergen epitopes. Moreover, a structural-variant FPH4 was calculated by in silico mutagenesis, rendering the protein unable to adopt the Bet v 1-like fold. Both molecules were produced in Escherichia coli, characterized physico-chemically as well as immunologically, and tested in mouse models of allergic sensitization as well as allergy prophylaxis. Results Using spectroscopic analyses, both proteins were monomeric, and the secondary structure elements of FPH resemble the ones typical for Bet v 1-like proteins, whereas FPH4 showed increased amounts of unordered structure. Both molecules displayed reduced binding capacities of Bet v 1-specific IgE antibodies. However, in a mouse model, the proteins were able to induce high IgG titres cross-reactive with all parental allergens. Moreover, prophylactic treatment with the hybrid proteins prevented pollen extract-induced allergic lung inflammation in vivo. Conclusion The hybrid molecules showed a more efficient uptake and processing by dendritic cells resulting in a modified T cell response. The proteins had a lower IgE-binding capacity compared with the

  18. Peptide-based allergen specific immunotherapy for the treatment of allergic disorders.

    PubMed

    El-Qutob, David; Reche, Pedro; Subiza, José L; Fernández-Caldas, Enrique

    2015-01-01

    Allergen specific immunotherapy (ASIT) and environmental control are the only etiologic treatments of allergic rhino-conjunctivitis, asthma and atopic dermatitis. The clinical benefit of ASIT relies on the selection of the patients and the identification and administration of the allergen, or allergens. Different routes of administration have been investigated, including subcutaneous, intradermal, epicutaneous, sublingual, inhaled, or intra-lymphatic. While subcutaneous and sublingual allergen specific immunotherapy may require from 3 to 5 years of treatment, clinical efficacy with intra-lymphatic treatment can be achieved after 3 injections. The most severe side effect of ASIT is anaphylaxis. Novel approaches are being investigated to reduce the allergenicity of immunotherapy vaccines, maintaining immunogenicity. Peptide immunotherapy has been directed mostly against autoimmune diseases, but the use of synthetic peptides for ASIT is a promising field in basic science, applied immunology and in clinical development. Short synthetic peptides bear allergen-specific CD4 T-cell epitopes which induce tolerance by stimulating regulatory (Treg) and Th1 cells. In the present patent review, we describe new trends in allergen immunotherapy using peptides, which, from a clinical point of view, are promising. PMID:25760734

  19. International consensus on allergy immunotherapy.

    PubMed

    Jutel, Marek; Agache, Ioana; Bonini, Sergio; Burks, A Wesley; Calderon, Moises; Canonica, Walter; Cox, Linda; Demoly, Pascal; Frew, Antony J; O'Hehir, Robin; Kleine-Tebbe, Jörg; Muraro, Antonella; Lack, Gideon; Larenas, Désirée; Levin, Michael; Nelson, Harald; Pawankar, Ruby; Pfaar, Oliver; van Ree, Ronald; Sampson, Hugh; Santos, Alexandra F; Du Toit, George; Werfel, Thomas; Gerth van Wijk, Roy; Zhang, Luo; Akdis, Cezmi A

    2015-09-01

    Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the World Allergy Organization, has decided to issue an international consensus on AIT. PMID:26162571

  20. Guidelines for the use of allergen immunotherapy. Canadian Society of Allergy and Clinical Immunology.

    PubMed Central

    1995-01-01

    OBJECTIVES: To recommend guidelines for the use of allergen immunotherapy to treat allergies in patients for whom allergen avoidance and drug therapy have not been sufficiently effective. OPTIONS: High-dose or low-dose allergen immunotherapy for the treatment of IgE-mediated allergy to insect stings, allergic rhinoconjunctivitis and asthma. OUTCOMES: Clinical evaluation of symptoms, objective measurement of reactions to nasal or bronchial allergen challenge, immunologic changes as a result of allergen immunotherapy and, among patients with anaphylactic reactions to stinging insects, clinical outcome of intentional sting challenge. EVIDENCE: A search of MEDLINE was conducted to identify articles that presented results of allergen immunotherapy. Proceedings of symposia held by international subcommittees and of consensus meetings, as well as references obtained from these sources, were reviewed. The articles were grouped according to their main subject: immunologic effects, specific allergies, the results of randomized placebo-controlled clinical trials, types of allergen extract and protocols for allergen immunotherapy, adverse effects and deficiencies of allergen immunotherapy. VALUES: Each member of the working group assessed the importance of such issues as basic immunologic effects, clinical efficacy, adverse effects and inappropriate use; the working group then arrived at a consensus. BENEFITS, HARMS AND COSTS: Implementation of these guidelines would lead to the appropriate use of allergen immunotherapy and control inappropriate treatment, which could result in adverse effects and increased costs of services for patients with allergies. RECOMMENDATIONS: Allergen immunotherapy with specific, standardized allergenic materials, administered in high-dose schedules, is effective in patients with an allergy to insect stings or allergic rhinoconjunctivitis, and in some patients with asthma, who have been correctly diagnosed through a meticulous history corroborated

  1. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

    PubMed

    Ryan, John F; Hovde, Rachel; Glanville, Jacob; Lyu, Shu-Chen; Ji, Xuhuai; Gupta, Sheena; Tibshirani, Robert J; Jay, David C; Boyd, Scott D; Chinthrajah, R Sharon; Davis, Mark M; Galli, Stephen J; Maecker, Holden T; Nadeau, Kari C

    2016-03-01

    Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation. PMID:26811452

  2. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets

    PubMed Central

    Ryan, John F.; Hovde, Rachel; Glanville, Jacob; Lyu, Shu-Chen; Ji, Xuhuai; Gupta, Sheena; Tibshirani, Robert J.; Jay, David C.; Boyd, Scott D.; Chinthrajah, R. Sharon; Davis, Mark M.; Galli, Stephen J.; Maecker, Holden T.; Nadeau, Kari C.

    2016-01-01

    Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional “roadmap” of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an “anergic” Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation. PMID:26811452

  3. Cockroach allergy and allergen-specific immunotherapy in asthma: Potential and Pitfalls

    PubMed Central

    Bassirpour, Gillian; Zoratti, Edward

    2014-01-01

    Purpose of review To provide a summary and discussion of cockroach allergy and clinical trials of cockroach allergen immunotherapy. Recent findings Cockroach allergen exposure among sensitized children is increasingly recognized as a key factor contributing to asthma morbidity. Recent trials suggest that cockroach immunotherapy has promise as a treatment strategy with studies demonstrating immunomodulatory and clinical effects. However, a few obstacles need to be overcome to realize the full potential of this treatment modality as cockroach allergic patients often exhibit complex sensitization patterns to multiple cockroach-associated proteins and an immunodominant allergen has not been identified. These factors have made it difficult to produce standardized cockroach allergen extracts that are potent and provide the broad allergen profiles needed for optimal treatment. There have been important advances in the identification and cloning of cockroach allergens and several strategies are being developed to provide therapeutic cockroach allergen products with enhanced clinical efficacy. Summary Allergen immunotherapy has the capability of modulating the immune response to cockroach allergen and has potential as a valuable treatment modality. Further studies of the clinical efficacy along with the development of improved therapeutic products are needed to advance our knowledge and realize the full potential of this promising therapy. PMID:25144264

  4. Grass pollen immunotherapy: where are we now.

    PubMed

    Würtzen, Peter A; Gupta, Shashank; Brand, Stephanie; Andersen, Peter S

    2016-04-01

    During allergen immunotherapy (AIT), the allergic patient is exposed to the disease-inducing antigens (allergens) in order to induce clinical and immunological tolerance and obtain disease modification. Large trials of grass AIT with highly standardized subcutaneous and sublingual tablet vaccines have been conducted to document the clinical effect. Induction of blocking antibodies as well as changes in the balance between T-cell phenotypes, including induction of regulatory T-cell subtypes, have been demonstrated for both treatment types. These observations increase the understanding of the immunological mechanism behind the clinical effect and may make it possible to use the immunological changes as biomarkers of clinical effect. The current review describes the recent mechanistic findings for subcutaneous immunotherapy and sublingual immunotherapy/tablet treatment and discusses how the observed immunological changes translate into a scientific foundation for the observed clinical effects of grass pollen immunotherapy and lead to new treatment strategies for grass AIT. PMID:26973122

  5. Allergen immunotherapy with nanoparticles containing lipopolysaccharide from Brucella ovis.

    PubMed

    Gómez, Sara; Gamazo, Carlos; San Roman, Beatriz; Ferrer, Marta; Sanz, Maria Luisa; Espuelas, Socorro; Irache, Juan M

    2008-11-01

    The adjuvant and protective capacity against anaphylactic shock of the association between rough lipopolysaccharide of Brucella ovis (LPS) coencapsulated with ovalbumin (OVA), as a model allergen, in Gantrez AN nanoparticles was investigated. Several strategies were performed in order to study the adjuvant effect of the LPS either encapsulated or coating the nanoparticles. OVA, as well as LPS, was incorporated either during the manufacturing process (OVA-encapsulated or LPS-encapsulated nanoparticles, respectively) or after the preparation (OVA-coated or LPS-coated nanoparticles, respectively). After the administration of 10 microg of OVA incorporated in the different formulations, all the nanoparticles, with or without LPS, were capable of amplifying the immune response (IgG(1) and IgG(2a)). However, in a model of sensitized mice to OVA, the formulation with OVA and LPS-entrapped inside the nanoparticles administered intradermally in three doses of 3 microg of OVA each was the only treatment that totally protected the mice from death after a challenge with an intraperitoneal injection of OVA. In contrast, the control group administered with OVA adsorbed onto a commercial alhydrogel adjuvant showed 80% mortality. These results are highly suggestive for the valuable use of Gantrez nanoparticles combined with rough LPS of B. ovis in immunotherapy. PMID:18582571

  6. [Recombinant allergens for diagnosis and specific immunotherapy--value in pediatric patients].

    PubMed

    Couderc, Rémy; Just, Jocelyne

    2013-03-01

    Identification of culprit allergens is important for prophylactic measures and specific allergen immunotherapy (SIT). Since the late 1980s, the use of molecular cloning technology has led to a major improvement in our knowledge of epitopes involved in IgE-mediated allergy, and has also allowed in vitro production of recombinant allergens of interest for the diagnosis of allergenic sensitization. It has also improved our understanding of allergen cross-reactivity, which can be responsible for severe clinical manifestations, particularly in children with food allergy and allergic asthma. Better knowledge of molecular and cellular mechanisms of allergenic sensitization, based on the use of natural or modified recombinant allergens, has led to the development of effective SIT strategies which, in the foreseeable future, could provide genuine cure, therefore avoiding use of symptomatic therapeutics, starting very early in childhood. PMID:25163347

  7. An Examination of Clinical and Immunologic Outcomes in Food Allergen Immunotherapy by Route of Administration.

    PubMed

    Chiang, David; Berin, M Cecilia

    2015-06-01

    Allergen immunotherapy for the treatment of food allergy has been a subject of intensive study within the last 10 years. After an unsuccessful attempt with subcutaneous immunotherapy for peanut allergy, other routes with varying degrees of safety and efficacy have been tested for peanut, milk, and egg allergies. In this review, we summarize the results to date with oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy for the treatment of food allergy. While results of immunotherapy trials are promising, increases in efficacy are commonly associated with an increased side effect profile. There is a need for additional research beginning at the preclinical level to develop safe and effective treatments for food allergy. PMID:26141581

  8. Hypoallergenic molecules for subcutaneous immunotherapy.

    PubMed

    Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K

    2016-01-01

    Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field. PMID:26558320

  9. The anti-vaccination movement and resistance to allergen-immunotherapy: a guide for clinical allergists.

    PubMed

    Behrmann, Jason

    2010-01-01

    Despite over a century of clinical use and a well-documented record of efficacy and safety, a growing minority in society questions the validity of vaccination and fear that this common public health intervention is the root-cause of severe health problems. This article questions whether growing public anti-vaccine sentiments might have the potential to spill-over into other therapies distinct from vaccination, namely allergen-immunotherapy. Allergen-immunotherapy shares certain medical vernacular with vaccination (e.g., allergy shots, allergy vaccines), and thus may become "guilty by association" due to these similarities. Indeed, this article demonstrates that anti-vaccine websites have begun unduly discrediting this allergy treatment regimen. Following an explanation of the anti-vaccine movement, the article aims to provide guidance on how clinicians can respond to patient fears towards allergen-immunotherapy in the clinical setting. This guide focuses on the provision of reliable information to patients in order to dispel misconceived associations between vaccination and allergen-immunotherapy, and the discussion of the risks and benefits of both therapies in order to assist patients in making autonomous decisions about their choice of allergy treatment. PMID:20843332

  10. The anti-vaccination movement and resistance to allergen-immunotherapy: a guide for clinical allergists

    PubMed Central

    2010-01-01

    Despite over a century of clinical use and a well-documented record of efficacy and safety, a growing minority in society questions the validity of vaccination and fear that this common public health intervention is the root-cause of severe health problems. This article questions whether growing public anti-vaccine sentiments might have the potential to spill-over into other therapies distinct from vaccination, namely allergen-immunotherapy. Allergen-immunotherapy shares certain medical vernacular with vaccination (e.g., allergy shots, allergy vaccines), and thus may become "guilty by association" due to these similarities. Indeed, this article demonstrates that anti-vaccine websites have begun unduly discrediting this allergy treatment regimen. Following an explanation of the anti-vaccine movement, the article aims to provide guidance on how clinicians can respond to patient fears towards allergen-immunotherapy in the clinical setting. This guide focuses on the provision of reliable information to patients in order to dispel misconceived associations between vaccination and allergen-immunotherapy, and the discussion of the risks and benefits of both therapies in order to assist patients in making autonomous decisions about their choice of allergy treatment. PMID:20843332

  11. Mechanisms of allergen specific immunotherapy--T-cell tolerance and more.

    PubMed

    Jutel, M; Akdis, M; Blaser, K; Akdis, C A

    2006-07-01

    Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific T-regulatory (Treg) cells and T helper 2 cells appears to be decisive in the development of allergic and healthy immune response against allergens. Treg cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific T helper 2 cells in allergic individuals. A decrease in interleukin (IL)-4, IL-5 and IL-13 production by allergen-specific CD4+ T cells due to the induction of peripheral T cell tolerance is the most essential step in allergen-specific immunotherapy (SIT). Suppressed proliferative and cytokine responses against the major allergens are induced by multiple suppressor factors, such as cytokines like IL-10 and transforming growth factor (TGF)-beta and cell surface molecules like cytotoxic T lymphocyte antigen-4, programmed death-1 and histamine receptor 2. There is considerable rationale for targeting T cells to increase efficacy of SIT. Such novel approaches include the use of modified allergens produced using recombinant DNA technology and adjuvants or additional drugs, which may increase the generation of allergen-specific peripheral tolerance. By the application of the recent knowledge in Treg cells and related mechanisms of peripheral tolerance, more rational and safer approaches are awaiting for the future of prevention and cure of allergic diseases. PMID:16792576

  12. Determinants of efficacy and safety in epicutaneous allergen immunotherapy: summary of three clinical trials

    PubMed Central

    Senti, G; von Moos, S; Tay, F; Graf, N; Johansen, P; Kündig, T M

    2015-01-01

    The results of our third trial on epicutaneous allergen-specific immunotherapy (EPIT) will be presented and discussed in the context of our previous trials. This monocentric, placebo-controlled, double-blind phase I/IIa trial included 98 patients with grass pollen rhinoconjunctivitis. Prior to the pollen season 2009, patients received six patches (allergen extract: n = 48; placebo: n = 50) with weekly intervals, administered onto tape-stripped skin. Allergen EPIT produced a median symptom improvement of 48% in 2009 and 40% in the treatment-free follow-up year 2010 as compared to 10% and 15% improvement after placebo EPIT (P = 0.003). After allergen EPIT but not placebo EPIT, conjunctival allergen reactivity was significantly decreased and allergen-specific IgG4 responses were significantly elevated (P < 0.001). In conclusion, our three EPIT trials found that allergen EPIT can ameliorate hay fever symptoms. Overall, treatment efficacy appears to be determined by the allergen dose. Local side-effects are determined by the duration of patch administration, while risk of systemic allergic side-effects is related to the degree of stratum corneum disruption. PMID:25704072

  13. The efficiency of peptide immunotherapy for respiratory allergy.

    PubMed

    Incorvaia, Cristoforo; Montagni, Marcello; Ridolo, Erminia

    2016-06-01

    Allergen immunotherapy (AIT) was introduced more than a century ago and is yet the only disease-modifying treatment for allergy. AIT is currently conducted with whole allergen extracts and several studies clearly support its efficacy in the treatment of respiratory allergies, however the need for a long treatment - that affects costs and patients compliance - and possible IgE-mediated adverse events are still unresolved issues. Peptide immunotherapy is based on the use of short synthetic peptides which represent major T-cell epitopes of the allergen with markedly reduced ability to cross-link IgE and activate mast cells and basophils. Data from clinical trials confirmed the efficacy and tolerability of peptide immunotherapy in patients with cat allergy, with a sustained clinical effect after a short course treatment. Peptide therapy is a promising safe and effective new specific treatment for allergy to be developed for the most important allergens causing rhinitis or asthma. PMID:26901667

  14. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile.

    PubMed

    Calderón, M A; Simons, F E R; Malling, H-J; Lockey, R F; Moingeon, P; Demoly, P

    2012-03-01

    Allergen immunotherapy reorients inappropriate immune responses in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical tolerance. Although 40-75% of patients receiving SLIT experience mild, transient local reactions in the oral mucosa, these primary reactions rarely necessitate dose reduction or treatment interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal) diagnosed according to the World Allergy Organization criteria and relate this figure to the approximately 1 billion SLIT doses administered worldwide since 2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be characterized further. PMID:22150126

  15. Video Q&A: Allergies and allergen immunotherapy - an interview with Alfred William Frankland

    PubMed Central

    2014-01-01

    In this video Q&A, we talk to Dr Alfred William Frankland about the highlights of his career, including working alongside Sir Alexander Fleming, co-founding the British Allergy Society, and introducing pollen counts to UK weather forecasts. We also discuss his opinions on why misconceptions about allergies and allergen immunotherapy still exist. Please see related article: http://www.biomedcentral.com/1741-7015/11/255. PMID:24447813

  16. Video Q&A: allergies and allergen immunotherapy--an interview with Alfred William Frankland.

    PubMed

    Frankland, A William

    2014-01-01

    In this video Q&A, we talk to Dr Alfred William Frankland about the highlights of his career, including working alongside Sir Alexander Fleming, co-founding the British Allergy Society, and introducing pollen counts to UK weather forecasts. We also discuss his opinions on why misconceptions about allergies and allergen immunotherapy still exist. Please see related article: http://www.biomedcentral.com/1741-7015/11/255. PMID:24447813

  17. Lung-derived innate cytokines: new epigenetic targets of allergen-specific sublingual immunotherapy

    PubMed Central

    Pishdadian, Abbas; Varasteh, Abdolreza; Gholamin, Mehran; Nasiraie, Leila Roozbeh; Hosseinpour, Mitra; Moghadam, Malihe; Sankian, Mojtaba

    2016-01-01

    Objective(s): Sublingual allergen-specific immunotherapy is a safe and effective method for treatment of IgE-mediated respiratory allergies; however, the underlying mechanisms are not fully understood. This study was planned to test whether sublingual immunotherapy (SLIT) can exert epigenetic mechanisms through which the airway allergic responses can be extinguished. Materials and Methods: BALB/c mice were sensitized intraperitoneally and challenged intranasally. Then, they received sublingual treatment with recombinant Che a 2 (rChe a 2), a major allergen of Chenopodium album. After SLIT, allergen-specific antibodies in sera, cytokine profiles of spleen cell cultures, mRNA and protein expression of lung-derived IL-33, IL-25, and TSLP (thymic stromal lymphopoietin), and histone modifications of these three genes were assessed. Results: Following Immunotherapy, systemic immune responses shifted from Th2 to Th1 profile as demonstrated by significant decrease in IgE and IL-4 and substantial increase in IgG2a and IFN-γ. At local site, mRNA and protein levels of lung-derived pro-inflammatory cytokines IL-33 and TSLP were markedly down-regulated following SLIT that was associated with marked enrichment of trimethylated lysine 27 of histone H3 at promoter regions of these two cytokines. Conclusion: In our study, sublingual immunotherapy with recombinant allergen effectively attenuated allergic immune responses, at least partly, by induction of distinct histone modifications at specific loci. Additionally, the lung-derived pro-allergic cytokines IL-33 and TSLP could be promising mucosal candidates for either monitoring allergic conditions or therapeutic approaches. PMID:27096066

  18. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    PubMed Central

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  19. Grass pollen sublingual immunotherapy and paediatric allergic rhinitis: A patient-oriented decision.

    PubMed

    Miceli Sopo, Stefano; Battista, Andrea; Greco, Monica; Monaco, Serena

    2016-01-01

    Guidelines and systematic review report that allergen immunotherapy (AIT) is, in general, effective in the treatment of allergic rhinitis. However, experts suggest not generalising the results of different clinical studies: for example, it would not be advisable to translate the results found in an adult population to a paediatric population or the results on the efficacy of AIT against a specific allergen to the AIT against a different allergen. Moreover, according to Evidence Based Medicine (EBM), clinical decisions are individualised and should derive from the "integration of best research evidence with clinical expertise and patient values". Taking into account the high specificity of the AIT and EBM principles, we tried to answer the question on how advisable it is to prescribe the AIT for the management of grass allergic rhinitis in children. To do this, we revised the scientific literature in order to solve a specific case scenario. PMID:26321601

  20. Allergen-Specific Immunotherapy in Patients 55 Years and Older: Results and Review of Literature

    PubMed Central

    Baptistella, Eduardo; Maniglia, Sergio; Malucelli, Diego Augusto; Rispoli, Daniel; Pruner de Silva, Thanara; Tsuru, Fernanda Miyoko; Becker, Renata Vecentin; Bernardi, Gustavo; Dranka, Daniela; Ferraz, Bruno

    2013-01-01

    Introduction Over the years the immune system suffers many morphologic and functional alterations, which result in a peak of function in puberty and a gradual decrease in the elderly. Aim Treat patients 55 years or older with allergic rhinitis with immunotherapy and then analyze the response to allergens. Materials and Methods From June 2009 to July 2010, 104 charts of patients 55 years or older with allergic complaints were evaluated. The patients were selected by anamnesis, physical examination, and otorhinolaryngologic exam. The patients had cutaneous test for mites before and after 1 year of sublingual specific immunotherapy. The cutaneous response was classified as negative (absent), light, moderate, or severe. Results Before vaccination, 42 (40.4%) patients were classified as having a severe form of allergy and 62 (59.6%) as having a moderate allergy. After the specific therapy, 40 (38.4%) patients were classified as negative (absent), 37 (35.6%) as light, 19 (18.3%) as moderate, and 8 (7.7%) as severe responses. Conclusion Immunotherapy, a desensitization technique, is indicated in cases which patients cannot avoid the exposure to allergens and in situations where pharmacologic therapy is not ideal. Specific immunotherapy to treat the allergic rhinitis in elderly patients was efficient and had no collateral effects, and in addition to the clinical benefit, improvement in the cutaneous test could also be observed. PMID:25992039

  1. Assessment of allergen-induced respiratory hyperresponsiveness before the prescription of a specific immunotherapy

    PubMed Central

    Argentão, Daiana Guedes Pinto; dos Santos Lima, Regiane Patussi; da Silva, Mariana Dias; dos Santos, Raquel Acácia Pereira Gonçalves; Fabbri, Natalia

    2015-01-01

    Background: Asymptomatic sensitization is a frequent condition that must be considered before the indication of allergic-specific immunotherapy. Objective: The aim of this study was to appreciate and correlate the local and spirometric changes elicited by the allergen-specific nasal provocation test (NPT) to define practical and feasible guidelines for the allergist/immunologist to demonstrate specific respiratory hyperresponsiveness before the indication of allergic-specific immunotherapy. Methods: A total of 172 subjects (children and adults) with a diagnosis of allergic rhinitis were submitted to flow-volume spirometry immediately before and after the NPT performed with Dermatophagoides antigens. The differences between the pre- and postspirometric estimated values of peak expiratory flow rate (PEFdif%), forced expiratory volume in 1 second (FEV1dif%), and forced vital capacity (FVCdif%) were correlated with the results of the nasal provocation test symptom score (NPT-SS). Results: There were 119 subjects (69%) with NPT-SS > 2. Among these patients who were reactive, the mean NPT-SS was 6.3. The Spearman's correlation between PEFdif% and NPT-SS was r = −0.44 (p = 0.01); the Spearman's correlation between FEV1dif% and NPT-SS was r = −0.22 (p = 0.01), and the Spearman's correlation between FVCdif% and NPT-SS was r = −0.21 (p = 0.04). Conclusion: The combined utilization of the allergen-specific NPT-SS with the spirometry (or PEF meter) is a safe methodology to evaluate allergen-specific nasal and bronchial hyperresponsiveness (which sometimes acts as a bronchial provocation test) in patients with allergic rhinitis and asthma due to hypersensitivity who are candidates for allergen-specific immunotherapy. PMID:26302728

  2. Aluminium in allergen-specific subcutaneous immunotherapy--a German perspective.

    PubMed

    Kramer, Matthias F; Heath, Matthew D

    2014-07-16

    We are living in an "aluminium age" with increasing bioavailability of the metal for approximately 125 years, contributing significantly to the aluminium body burden of humans. Over the course of life, aluminium accumulates and is stored predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of aluminium in humans is briefly summarised, highlighting links and possible causal relationships between a high aluminium body burden and a number of neurological disorders and disease states. Aluminium salts have been used as depot-adjuvants successfully in essential prophylactic vaccinations for almost 100 years, with a convincing positive benefit-risk assessment which remains unchanged. However, allergen-specific immunotherapy commonly consists of administering a long-course programme of subcutaneous injections using preparations of relevant allergens. Regulatory authorities currently set aluminium limits for vaccines per dose, rather than per treatment course. Unlike prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in subcutaneous immunotherapy (SCIT) and will significantly contribute to a higher cumulative life dose of aluminium. While the human body may cope robustly with a daily aluminium overload from the environment, regulatory cumulative threshold values in immunotherapy need further addressing. Based on the current literature, predisposing an individual to an unusually high level of aluminium, such as through subcutaneous immunotherapy, has the potential to form focal accumulations in the body with the propensity to exert forms of toxicity. Particularly in relation to longer-term health effects, the safety of aluminium adjuvants in immunotherapy remains unchallenged by health authorities - evoking the need for more consideration, guidance, and transparency on what is known and not known about its safety in long-course therapy and what measures can be taken to prevent or

  3. Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

    PubMed

    Datta, Ankur; Moitra, Saibal; Hazra, Iman; Mondal, Somnath; Das, Prasanta Kumar; Singh, Manoj Kumar; Chaudhuri, Suhnrita; Bhattacharya, Debanjan; Tripathi, Santanu Kumar; Chaudhuri, Swapna

    2016-01-01

    Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities. PMID:26667977

  4. [The immunological mechanisms contributing to the clinical efficacy of allergen specific immunotherapy (SIT) in allergic diseases].

    PubMed

    Asher, Ilan; Mahlab-Guri, Keren; Sthoeger, Zev

    2013-09-01

    The prevalence of allergic diseases has increased dramatically in the western world. In the last 2 decades, the frequency of asthma and allergic rhinitis has doubled. Allergen specific immunotherapy [SIT] has been used successfully for more than 100 years for the treatment of allergic disorders. Allergen SIT provides not only symptomatic relief, but it is potentially curative. The immunologic mechanisms of allergen SIT include all parts of the immune system. Regulatory T cells (TR1, Treg), have a major pivotal role in the success of immunotherapy. Along with the regulatory T cells, elevated suppressor cytokines (IL-10), suppression of TH2 cells, increasing titer of specific IgG4 and gradual decline in the number and function of basophils and mast cells also contribute to the success of the treatment (SIT). The above immune mechanisms are connected and related to each other acting at different times with the treatment with SIT. In this review we focused on the current knowledge and understanding of the different immune mechanisms which are involved in the success of SIT. PMID:24364093

  5. The Cloning and Expression of Human Monoclonal Antibodies: Implications for Allergen Immunotherapy.

    PubMed

    James, Louisa K

    2016-02-01

    Allergic responses are dependent on the highly specific effector functions of IgE antibodies. Conversely, antibodies that block the activity of IgE can mediate tolerance to allergen. Technologies that harness the unparalleled specificity of antibody responses have revolutionized the way that we diagnose and treat human disease. This area of research continues to advance at a rapid pace and has had a significant impact on our understanding of allergic disease. This review will present an overview of humoral responses and provide an up-to-date summary of technologies used in the generation of human monoclonal antibodies. The impact that monoclonal antibodies have on allergic disease will be discussed, with a particular focus on allergen immunotherapy, which remains the only form of treatment that can modulate the underlying immune mechanisms and induce long-term clinical tolerance. PMID:26780523

  6. Mechanisms of allergen-specific immunotherapy: T-regulatory cells and more.

    PubMed

    Verhagen, Johan; Blaser, Kurt; Akdis, Cezmi A; Akdis, Mübeccel

    2006-05-01

    Activation-induced cell death, anergy, or immune response modulation by regulatory T cells (Treg cells) are essential mechanisms of peripheral T-cell tolerance. Genetic predisposition and environmental instructions tune thresholds for the activation of T cells, other inflammatory cells, and resident tissue cells in allergic diseases. Skewing allergen-specific effector T cells to a Treg-cell phenotype seems to be crucial in maintaining a healthy immune response to allergens and successful allergen-specific immunotherapy. The Treg-cell response is characterized by an abolished allergen-specific T-cell proliferation and the suppressed secretion of T-helper 1- and T-helper 2-type cytokines. Suppressed proliferative and cytokine responses against allergens are induced by multiple suppressor factors, including cytokines such as interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), and cell surface molecules such as cytotoxic T-lymphocyte antigen-4, programmed death-1, and histamine receptor 2. The increased levels of IL-10 and TGF-beta produced by Treg cells potently suppress IgE production while simultaneously increasing the production of noninflammatory isotypes IgG4 and IgA, respectively. In addition, Treg cells directly or indirectly suppress the activity of effector cells of allergic inflammation, such as mast cells, basophils, and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms on T cells, regulation of antibody isotypes, and suppression of effector cells. The application of current knowledge of Treg cells and related mechanisms of peripheral tolerance may soon lead to more rational and safer approaches to the prevention and cure of allergic disease. PMID:16701141

  7. The potential role of allergen-specific sublingual immunotherapy in atopic dermatitis.

    PubMed

    Mastrandrea, Fulvio

    2004-01-01

    Atopic dermatitis is a chronic inflammatory skin disease associated with increasing prevalence, morbidity, and cost in developed Western countries. Frequently associated with respiratory allergy during adulthood, atopic dermatitis often represents the first phenotypic appearance of atopy in early childhood when the allergic 'march' starts and progressively moves toward food allergy, asthma, and rhinitis. At present, a consistent body of evidence supports the view that atopic dermatitis may represent the skin compartmentalization of a systemic allergic inflammation. Lymphocytes infiltrating early lesional skin express a T helper (Th) 2 pattern of cytokine secretion (increased levels of interleukin [IL]-4 and/or IL-13 and decreased levels of interferon-gamma) as well as the typical Th2-type chemokine receptor CCR4, specific to the thymus and activation-regulated chemokines. Keratinocytes from patients with atopic dermatitis produce thymic stromal lymphopoietin, a novel cytokine that supports the early lymphocyte development in mouse models, and activates dendritic cells involved in the pathogenesis of allergic diseases in humans. Increased levels of circulating hemopoietic precursor cells have been reported in atopic dermatitis, as in allergic asthma and rhinitis. Furthermore, the recognition of CD34+ hemopoietic precursor cells, and evidence for cellular differentiation/maturational events occurring within atopic dermatitis skin lesion infiltrates, are consistent with the recent reinterpretation of the Th2/Th1 paradigm, where Th2 cells appear to belong to the early stages and Th1 to the ultimate stages of a linear, rather than divergent, pattern of lymphoid differentiation. This more detailed understanding of the immunologic derangements contributing to the atopic dermatitis pathogenesis has led to growing interest in allergen-specific immunotherapy for the disease. Due to the complexity intrinsic to atopic dermatitis and the lack of consensus-based guidelines for

  8. Paradoxical Increase of IgE Binding Components during Allergen-Specific Immunotherapy in Pollinosis Patients

    PubMed Central

    Kim, Mi-Ae; Yoon, Moon-Gyung; Jin, Hyun-Jung; Shin, Yoo-Seob

    2014-01-01

    Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens. Graphical Abstract PMID:25045240

  9. Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis

    PubMed Central

    Babakhin, Alexander; Andreev, Sergey; Nikonova, Alexandra; Shilovsky, Igor; Buzuk, Andrey; Elisyutina, Olga; Fedenko, Elena; Khaitov, Musa

    2015-01-01

    Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD. PMID:26275152

  10. Paradoxical increase of IgE binding components during allergen-specific immunotherapy in pollinosis patients.

    PubMed

    Kim, Mi-Ae; Yoon, Moon-Gyung; Jin, Hyun-Jung; Shin, Yoo-Seob; Park, Hae-Sim

    2014-07-01

    Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens. PMID:25045240

  11. Bystander immunotherapy as a strategy to control allergen-driven airway inflammation.

    PubMed

    Navarro, S; Lazzari, A; Kanda, A; Fleury, S; Dombrowicz, D; Glaichenhaus, N; Julia, V

    2015-07-01

    Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), lung infiltration of Th2 cells, and high levels of IgE. To date, allergen-specific immunotherapy (SIT) is the only treatment that effectively alleviates clinical symptoms and has a long-term effect after termination. Unfortunately, SIT is unsuitable for plurisensitized patients, and highly immunogenic allergens cannot be used. To overcome these hurdles, we sought to induce regulatory CD4(+) T cells (Treg) specific to an exogenous antigen that could be later activated as needed in vivo to control allergic responses. We have established an experimental approach in which mice tolerized to ovalbumin (OVA) were sensitized to the Leishmania homolog of receptors for activated c kinase (LACK) antigen, and subsequently challenged with aerosols of LACK alone or LACK and OVA together. Upon OVA administration, AHR and allergic airway responses were strongly reduced. OVA-induced suppression was mediated by CD25(+) Treg, required CTLA-4 and ICOS signaling and resulted in decreased numbers of migrating airway dendritic cells leading to a strong impairment in the proliferation of allergen-specific Th2 cells. Therefore, inducing Treg specific to a therapeutic antigen that could be further activated in vivo may represent a safe and novel curative approach for allergic asthma. PMID:25425267

  12. Molecular biomarkers for grass pollen immunotherapy

    PubMed Central

    Popescu, Florin-Dan

    2014-01-01

    Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy (AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy (tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines. PMID:25237628

  13. Efficacy and safety of D. pteronyssinus immunotherapy in local allergic rhinitis: a double-blind placebo-controlled clinical trial.

    PubMed

    Rondón, C; Campo, P; Salas, M; Aranda, A; Molina, A; González, M; Galindo, L; Mayorga, C; Torres, M J; Blanca, M

    2016-07-01

    The effects of allergen immunotherapy (AIT) on local allergic rhinitis (LAR) are largely unknown. We conducted the first randomized, double-blind, placebo-controlled (DBPC), phase II trial of D. pteronyssinus (DP) subcutaneous AIT (DP-AIT) on LAR (clinicaltrials.gov identifier: NCT02123316). Thirty-six LAR patients received Pangramin PLUS DP or placebo for 24 months. The primary endpoints were symptoms, medication scores, and medication-free days. The secondary included skin test, serum specific IgE and IgG4, nasal allergen provocation test (NAPT), and adverse events. AIT-DP produced significant improvements in both primary and secondary endpoints vs placebo. After 12 months of AIT-DP, we detected a significant and marked increase in allergen tolerance with negative NAPT in 50% of patients, and significant increases of serum sIgG4. Immunotherapy was well tolerated; no systemic reactions were reported. This study demonstrated that AIT-DP is a safe and clinically effective treatment for LAR, confirming that LAR is a new indication for AIT. PMID:27008542

  14. IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma.

    PubMed

    Böhm, Livia; Maxeiner, Joachim; Meyer-Martin, Helen; Reuter, Sebastian; Finotto, Susetta; Klein, Matthias; Schild, Hansjörg; Schmitt, Edgar; Bopp, Tobias; Taube, Christian

    2015-02-01

    Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells. PMID:25527785

  15. Specific immunotherapy with mugwort pollen allergoid reduce bradykinin release into the nasal fluid

    PubMed Central

    Grzanka, Alicja; Jawor, Barbara; Czecior, Eugeniusz

    2016-01-01

    Introduction A pathomechanism of allergic rhinitis is complex. A neurogenic mechanism seems to play a significant role in this phenomenon. Aim The evaluation of influence of specific immunotherapy of mugwort pollen allergic patients on the bradykinin concentration in the nasal lavage fluid. Material and methods The study included 22 seasonal allergic rhinitis patients. Thirty persons with monovalent allergy to mugwort pollen, confirmed with skin prick tests and allergen-specific immunoglobulin E, underwent a 3-year-long allergen immunotherapy with the mugwort extract (Allergovit, Allergopharma, Germany). The control group was composed of 9 persons with polyvalent sensitivity to pollen, who were treated with pharmacotherapy. Before the allergen-specific immunotherapy (AIT) and in subsequent years before the pollen seasons, a provocation allergen test with the mugwort extract was performed, together with collection of nasal fluids, where bradykinin concentration was determined according to Proud method. Results There were similar levels of bradykinin in both groups at baseline prior to therapy (AIT group: 584.0 ±87.2 vs. controls 606.3 ±106.5 pg/ml) and changes after allergen challenge 1112.4 ±334.8 vs. 1013.3 ±305.9 pg/ml as well. The bradykinin concentration in nasal lavage fluid after mugwort challenge in 1 year was lower in the AIT group (824.1 ±184.2 pg/ml vs. 1000.4 ±411.5 pg/l; p < 005) with a further significant decrease after the 2nd and 3rd year of specific immunotherapy. Significant reduction of symptoms and medications use was observed in hyposensitized patients. Conclusions A decreased level of bradykinin as a result of AIT suggests that some of the symptomatic benefits of AIT may be related to the reduced release of bradykinin into nasal secretions. These values correlate with clinical improvement within the course of treatment. PMID:27605897

  16. Effects of sublingual immunotherapy on allergic inflammation: an update.

    PubMed

    Yacoub, Mona-Rita; Colombo, Giselda; Marcucci, Francesco; Caminati, Marco; Sensi, Laura; Di Cara, Giuseppe; Frati, Franco; Incorvaia, Cristoforo

    2012-08-01

    The most common allergic diseases, and especially the respiratory disorders such as rhinitis and asthma, are closely related to the allergic inflammation elicited by the causative allergen. This makes inflammation the main target of anti-allergic therapies. Among the available treatments, allergen specific immunotherapy (AIT) has a patent effect on allergic inflammation, which persists also after its discontinuation, and is the only therapy able to modify the natural history of allergy. The traditional, subcutaneous route of administration was demonstrated to modify the allergen presentation by dendritic cells (DCs) that in turn correct the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation and characterized by the production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines to a Th1-type response. This immune deviation is related to an increased IFN-gamma and IL-2 production as well as to the anergy of Th2 or to tolerance, the latter being related to the generation of allergen-specific T regulatory (Treg) cells, which produce cytokines such as IL-10 and TGF-beta. Anti-inflammatory mechanisms observed during sublingual AIT with high allergen doses proved to be similar to subcutaneous immunotherapy. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa, with particular importance for mucosal DCs, plays a crucial role in inducing tolerance to the administered allergen. PMID:22506880

  17. Contact allergy in atopic individuals in relation to allergen-specific immunotherapy.

    PubMed

    Siemund, Ingrid; Hindsén, Monica; Netterlid, Eva; Güner, Nuray; Bruze, Magnus

    2016-06-01

    Type I sensitizations and atopic dermatitis (AD) often appear in the same patient. Beneficial effects of allergen-specific immunotherapy (ASIT) in patients with both AD and type I allergies have been reported. The predisposing role of AD to the development of type IV sensitization is discussed. Whether ASIT for type I allergy also influences type IV allergies is unknown. To compare the number of contact allergies between patients with and without AD, before and after one year's treatment with ASIT. A controlled, single-blind multicentre study of children/adults with allergic asthma and/or rhinoconjunctivitis, treated or untreated with ASIT, was performed. The history of AD was collected using questionnaires. The number of contact allergies was assessed by patch testing with a baseline series. 205 individuals completed the study; 133 treated with ASIT (exposed) and 72 before starting ASIT (unexposed). For participants with AD, significantly more contact allergies were found in the groups of all children (p = 0.002), all exposed children (p<0.001), and all exposed study persons (p = 0.013). Independent of AD, significantly more contact allergies were noted in the groups of all unexposed adults (p = 0.004) and all unexposed study persons (p = 0.004). The higher number of contact allergies in patients with AD indicates that AD may be a risk factor for type IV sensitization in those with allergic asthma and/or rhinoconjunctivitis. The lower number of contact allergies in patients exposed to ASIT suggests an immunomodulatory effect on type IV sensitization. PMID:27193374

  18. Sublingual immunotherapy: World Allergy Organization position paper 2013 update.

    PubMed

    Canonica, Giorgio Walter; Cox, Linda; Pawankar, Ruby; Baena-Cagnani, Carlos E; Blaiss, Michael; Bonini, Sergio; Bousquet, Jean; Calderón, Moises; Compalati, Enrico; Durham, Stephen R; van Wijk, Roy Gerth; Larenas-Linnemann, Désirée; Nelson, Harold; Passalacqua, Giovanni; Pfaar, Oliver; Rosário, Nelson; Ryan, Dermot; Rosenwasser, Lanny; Schmid-Grendelmeier, Peter; Senna, Gianenrico; Valovirta, Erkka; Van Bever, Hugo; Vichyanond, Pakit; Wahn, Ulrich; Yusuf, Osman

    2014-01-01

    We have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2009", available at http://www.waojournal.org. Namely, these comprise: "Mechanisms of sublingual immunotherapy;" "Clinical efficacy of sublingual immunotherapy" - reporting all the data of all controlled trials published after 2009; "Safety of sublingual immunotherapy" - with the recently published Grading System for adverse reactions; "Impact of sublingual immunotherapy on the natural history of respiratory allergy" - with the relevant evidences published since 2009; "Efficacy of SLIT in children" - with detailed analysis of all the studies; "Definition of SLIT patient selection" - reporting the criteria for eligibility to sublingual immunotherapy; "The future of immunotherapy in the community care setting"; "Methodology of clinical trials according to the current scientific and regulatory standards"; and "Guideline development: from evidence-based medicine to patients' views" - including the evolution of the methods to make clinical recommendations.Additionally, we have added new chapters to cover a few emerging crucial topics: "Practical aspects of schedules and dosages and counseling for adherence" - which is crucial in clinical practice for all treatments; "Perspectives and new approaches" - including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, "Raising public awareness about sublingual immunotherapy", as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  19. Safety of ragweed sublingual allergy immunotherapy tablets in adults with allergic rhinoconjunctivitis.

    PubMed

    Nayak, Anjuli S; Atiee, George J; Dige, Ea; Maloney, Jennifer; Nolte, Hendrik

    2012-01-01

    A sublingually administered allergy immunotherapy tablet (AIT) is under development to treat ragweed (Ambrosia artemisiifolia)-induced allergic rhinoconjunctivitis (ARC). This study investigates the optimal tolerable dose of once daily ragweed pollen AIT.Subjects 18-50 years old with ragweed-induced ARC were enrolled at two U.S. centers in a double-blind, placebo-controlled,dose-escalation study outside ragweed season. Groups (12 subjects each) were to be randomized 3:1 to 28 days of active treatment (groups assigned in sequence to 3, 6, 12, 24, 50, or 100 units of Ambrosia artemislifolia major allergen 1 [Amb a 1 U],without dose buildup at any level) or matching placebo. Recruitment to 50 Amb a 1-U was discontinued because of adverse events (AEs) after four AIT subjects were enrolled; 100 Amb a 1-U was not initiated. Fifty-three subjects were randomized (AIT,n = 40; placebo, n = 13); four discontinued, all because of AEs (AIT, n = 3; placebo, n = 1). Treatment-related AEs (TRAEs) were more frequent with AIT (73%) than placebo (31%), increasing with dose level. AIT TRAEs were mostly mild (94%) or moderate(5%). No serious TRAEs or anaphylactic shock occurred. The most common TRAEs with AIT were localized pruritus, nasal irritation, and throat irritation. Median onset for common AIT application site reactions was 24 ≤ hours after first treatment (median duration, 15-50 minutes). AIT increased immunoglobulin (Ig) significantly more than placebo (ragweed-specific IgE [6, 12, and 24 Amb a 1-U]; IgG4 [all doses]; p < 0.05). Three subjects in dose groups ≥ 24 Amb a 1-U experienced symptoms suggestive of systemic reaction. Of tested doses, ragweed AIT 24

  20. Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus immunotherapy response

    PubMed Central

    Fernández, Tahia D.; Gómez, Enrique; Doña, Inmaculada; Campo, Paloma; Rondon, Carmen; Gonzalez, Miguel; Gomez, Francisca; Palomares, Francisca; Salas, Maria; Blanca, Miguel; Mayorga, Cristobalina; Torres, Maria J.

    2015-01-01

    Allergic rhinitis is highly prevalent worldwide. Immunotherapy has been shown to control its symptoms, however, up to 30% of patients may not respond. Previous studies of the immunological mechanisms involved in allergen-immunotherapy (AIT) have focused on the humoral and T-cell response and several studies have evaluated some B-cell subpopulations during AIT and their role in immunological tolerance. However, although B and plasma-cell subpopulations are two of the most important cellular subtypes involved in allergic reactions, their relation with AIT efficacy remains unelucidated. The objective was to analyze the effects of immunotherapy on different B and plasma-cell subpopulations and whether these changes correlate with the clinical response to the treatment. Although no changes are found in B-cell subpopulations, responder patients show increased levels of memory B-cells even before the beginning of treatment. Changes in plasma-cell subpopulations are found, mainly in circulating inflammatory plasma-cells that could affect the response to the allergen. Moreover, an early increase of specific-IgG4 and IgG4 secreting-cells was found. All these suggest that the determination of the memory B-cells before the initiation of the treatment, and the quantification of IgG4 and IgG4-secreting-cells in the first months of immunotherapy, could serve as markers for the clinical response to treatment. PMID:26416023

  1. Immunotherapy in all aspects.

    PubMed

    Hanci, Deniz; Şahin, Ethem; Muluk, Nuray Bayar; Cingi, Cemal

    2016-06-01

    Allergen immunotherapy is a form of long-term treatment that decreases symptoms for many people with allergic rhinitis, allergic asthma, conjunctivitis (eye allergy) or stinging insect allergy. In this review, we presented the important topics in immunotherapy. The important aspects of immunotherapy are considered to be "Immunologıcal responses to immunotherapy"; "The principal types of immunotherapy"; "Effectiveness"; "Indications"; "Contraindications"; "Allergen immunotherapy in children"; "Safety"; and "Anaphylactic reactions after immunotherapy". The principal types of immunotherapy are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy. Both of them can be used in indicated cases. When using SCIT, physicians must be more careful because of reported rare fatal cases. The risks and benefits of continuing allergen immunotherapy in patients who have experienced severe systemic reactions should be carefully considered. PMID:25673026

  2. FoxP3 Tregs Response to Sublingual Allergen Specific Immunotherapy in Children Depends on the Manifestation of Allergy

    PubMed Central

    Stelmaszczyk-Emmel, Anna; Zawadzka-Krajewska, Anna; Głodkowska-Mrówka, Eliza; Demkow, Urszula

    2015-01-01

    Over the last decades allergic diseases has become a major health problem worldwide. The only specific treatment to date is allergen specific immunotherapy (ASIT). Although it was shown that ASIT generates allergen-tolerant T cells, detailed mechanism underlying its activity is still unclear and there is no reliable method to monitor its effectiveness. The aim of our study was to evaluate ASIT influence on the frequency of forkhead box P3 (FoxP3) Tregs in allergic children with various clinical manifestations. The relative number of FoxP3 Tregs in 32 blood samples from allergic children at baseline and/or after 1 year of ASIT was assessed by flow cytometry. In the entire studied group, the percentage of FoxP3 Tregs did not increase 1 year after ASIT. Nevertheless, the percentage of FoxP3 Tregs after ASIT significantly increased in children with respiratory allergy (conjunctivitis, asthma, and rhinitis) coexisting with nonrespiratory manifestations (food allergy and/or atopic dermatitis), whereas, in patients with respiratory allergy only, the percentage of FoxP3 Tregs decreased. To the best of our knowledge, this is the first report showing various differential FoxP3 Tregs response to ASIT in allergic children. FoxP3 Tregs number could be useful in treatment monitoring. Further studies are warranted to confirm these observations. PMID:26457309

  3. FoxP3 Tregs Response to Sublingual Allergen Specific Immunotherapy in Children Depends on the Manifestation of Allergy.

    PubMed

    Stelmaszczyk-Emmel, Anna; Zawadzka-Krajewska, Anna; Głodkowska-Mrówka, Eliza; Demkow, Urszula

    2015-01-01

    Over the last decades allergic diseases has become a major health problem worldwide. The only specific treatment to date is allergen specific immunotherapy (ASIT). Although it was shown that ASIT generates allergen-tolerant T cells, detailed mechanism underlying its activity is still unclear and there is no reliable method to monitor its effectiveness. The aim of our study was to evaluate ASIT influence on the frequency of forkhead box P3 (FoxP3) Tregs in allergic children with various clinical manifestations. The relative number of FoxP3 Tregs in 32 blood samples from allergic children at baseline and/or after 1 year of ASIT was assessed by flow cytometry. In the entire studied group, the percentage of FoxP3 Tregs did not increase 1 year after ASIT. Nevertheless, the percentage of FoxP3 Tregs after ASIT significantly increased in children with respiratory allergy (conjunctivitis, asthma, and rhinitis) coexisting with nonrespiratory manifestations (food allergy and/or atopic dermatitis), whereas, in patients with respiratory allergy only, the percentage of FoxP3 Tregs decreased. To the best of our knowledge, this is the first report showing various differential FoxP3 Tregs response to ASIT in allergic children. FoxP3 Tregs number could be useful in treatment monitoring. Further studies are warranted to confirm these observations. PMID:26457309

  4. [Allergen-specific immunotherapy for food allergies in childhood. Current options and future perspectives].

    PubMed

    Trendelenburg, Valérie; Blümchen, Katharina

    2016-07-01

    During recent years increasing research has been conducted on casual treatment options for food allergy, with focus on oral immunotherapy (OIT) for hen's egg, cow's milk and peanut allergy. Several studies could show that OIT leads to desensitization or an increase of threshold. However, severe adverse events during this treatment are not uncommon. Whether OIT leads to a sustained, 'robust' development of tolerance in patients has not yet been thoroughly investigated. Besides OIT, some studies on sublingual (SLIT) and epicutaneous immunotherapy (EPIT) were performed, aiming to improve the safety profile. Furthermore, there are some pilot studies investigating a combined treatment of SLIT and OIT or a combined use of anti-IgE treatment or probiotic supplementation with OIT. Further placebo-controlled trials with larger sample size are needed in order to develop standardized protocols before immunotherapy may be used as a therapeutic option for food allergy outside of clinical trials. PMID:27324376

  5. From Allergen Back to Antigen:. a Rational Approach to New Forms of Immunotherapy

    NASA Astrophysics Data System (ADS)

    Colombo, Paolo; Trapani, Antonino; Geraci, Domenico; Golino, Massimiliano; Gianguzza, Fabrizio; Bonura, Angela

    2007-12-01

    Mapping an epitope on a protein by gene fragmentation and/or point mutations is often expensive and time consuming. Analysis of a 3D model can be utilized to detect the amino acids residues which are exposed to the solvent surface and thus represent potential epitope residues. Parj1 and Parj2 are the two major allergens of the Parietaria judaica pollen belonging to the Lipid Transfer Protein family. Using their three-dimensional structures as a guide, a head to tail dimer expressing disulphide bond variants of the major allergens was generated by means of DNA recombinant technology. The hybrid was expressed in E.coli and its immunological activity studied in vivo and in vitro. Our results demonstrate that a hybrid polypeptide expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and enhanced T cell reactivity for induction of protective antibodies able to block human IgE induced during the natural course of sensitization against the Parietaria pollen.

  6. Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy

    PubMed Central

    Luo, Xi; Hong, Haiyu; Tang, Jun; Wu, Xingmei; Lin, Zhibin; Ma, Renqiang; Fan, Yunping; Xu, Geng

    2016-01-01

    Purpose MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Methods Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. Results After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. Conclusions Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR. PMID:26739406

  7. Lymphocyte transformation by grass pollen allergens: a study of atopic patients receiving immunotherapy. Part II. Patients during maintenance treatment.

    PubMed

    Broman, P; Möller, E

    1988-07-01

    We have previously reported on peripheral blood lymphocyte (PBL) transformation by allergen, PPD as a control antigen and PHA as a mitogen during and after a preseasonal immunotherapy period. The present report describes similar parameters during and after the ensuing maintenance treatment period. Ten patients with grass pollen rhinitis were treated with Allpyral extract and 10 with Conjuvac two-grass mixture. Lymphocyte transformation responses to grass antigen continued to be low for PBL from patients during the maintenance treatment. Postseasonal values were higher during treatment. In late autumn 1980, when treatment had been stopped, there was a spontaneous fall in lymphocyte stimulation values. Occasional high values were noticed in some patients, two of whom had treatment side effects (urticaria). Clinical data during the whole treatment period (skin prick test, provocation tests, serological parameters, total IgE, grass-specific IgE, grass-specific IgG, pollen counts, symptom scores, clinical effect and adverse reactions) have been published separately. PMID:3414911

  8. Revisiting Desensitization and Allergen Immunotherapy Concepts for the International Classification of Diseases (ICD)-11.

    PubMed

    Tanno, Luciana Kase; Calderon, Moises A; Papadopoulos, Nikolaos G; Sanchez-Borges, Mario; Rosenwasser, Lanny J; Bousquet, Jean; Pawankar, Ruby; Sisul, Juan Carlos; Cepeda, Alfonso Mario; Li, James; Muraro, Antonella; Fineman, Stanley; Sublett, James L; Katelaris, Constance H; Chang, Yoon-Seok; Moon, Hee-Bom; Casale, Thomas; Demoly, Pascal

    2016-01-01

    Allergy and hypersensitivity intervention management procedures, such as desensitization and/or tolerance induction and immunotherapy, have not been pondered up to now in the content of International Classification of Diseases (ICD) context because the focus has been on prioritizing the condition implementations. Tremendous efforts have been devoted to implementing allergic and hypersensitivity conditions in the forthcoming ICD-11. However, we consider that it is crucial now to have nomenclature and classification universally accepted for these procedures to be able to provide scientifically consistent proposals into the new ICD-11 platform for the best practice parameters of our specialty. With the aim of promoting a harmonized comprehension and aligning it with the ICD-11 revision, we have reviewed the definitions and concepts currently used for desensitization and/or tolerance induction and immunotherapy. We strongly believe that this review is a key instrument to support the allergy specialty identity into the ICD-11 framework and serves as a platform to perform positive quality improvement in clinical practice. PMID:26969269

  9. Is There Any Parameter Helpful for Predicting a Suitable Candidate for Mite Immunotherapy?

    PubMed

    Karaman, Sait; Can, Demet; Erdem, Semiha Bahçeci; Nacaroğlu, Hikmet Tekin; Karkıner, Canan Şule; Günay, İlker

    2016-04-01

    Few biomarkers that can predict the clinical response to allergen immunotherapy (AIT) have been identified. The aim of the present study was to investigate parameters that could be used "in predicting the clinical response to AIT" in children with asthma caused by house dust mites. We evaluated 107 children with mild persistent asthma who were sensitised only to mite aeroallergens. The study group included 47 patients who underwent a 4-to-5-year course of subcutaneous immunotherapy with standardised mite allergenic extract. Sixty patients who had not undergone AIT but were allergic to house mites were included in the control group. The clinical features and laboratory parameters of patients who did and did not sustain remission were compared. Remission was achieved in 74.5% of the 47 patients in the study group and in 20% of those in the control group. In the study group, one parameter predictive of a clinical response to AIT was identified by multivariate logistic analysis. This parameter was the serum total IgE level (tIgE) at the time of diagnosis (OR 131.64 and CI 0.858-20193; p = 0.032). Serum tIgE levels ≤ 339 kU/L at diagnosis were associated with an effective clinical response to AIT, with a sensitivity of 64.5% and specificity of 88.9%. We conclude that measurement of the serum tIgE level can be used as a predictive test prior to AIT in patients sensitized to mite aeroallergens. PMID:27090363

  10. Adherence to Sublingual Immunotherapy.

    PubMed

    Incorvaia, Cristoforo; Mauro, Marina; Leo, Gualtiero; Ridolo, Erminia

    2016-02-01

    Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. PMID:26758865

  11. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    PubMed Central

    2014-01-01

    We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  12. Grass-specific CD4+ T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy

    PubMed Central

    Archila, LD; DeLong, JH; Wambre, E; James, EA; Robinson, DM; Kwok, WW

    2014-01-01

    Background Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity amongst grass pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. Objectives We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4+ T cell level amongst DR04:01 restricted Pooideae grass pollen T-cell epitopes. Methods After In vitro culture of blood mononucleated cells from Grass-pollen allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labeled DR04:01/Phleum pratense tetramers and PE-labeled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity amongst allergen-specific DR04:01-restricted T-cells in 6 subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. Results T-cells with various degree of cross reactive profiles could be detected. Poa p 1 97-116, Lol p 1 221-240, Lol p 5a 199-218, and Poa p 5a 199-218 were identified as minimally-cross-reactive T-cell epitopes that do not show cross reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally-cross reactive T-cell epitopes are present in Grass-pollen allergic subjects. Conclusions Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells, suggest that a multiple allergen system should be considered for immunotherapy instead of a mono allergen system. PMID:24708411

  13. Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens

    PubMed Central

    Vickery, Brian P.; Lin, Jing; Kulis, Michael; Fu, Zhiyan; Steele, Pamela H.; Jones, Stacie M.; Scurlock, Amy M.; Gimenez, Gustavo; Bardina, Ludmilla; Sampson, Hugh A.; Burks, A. Wesley

    2012-01-01

    Background Peanut-allergic subjects have highly stable pathologic antibody repertoires to the immunodominant B cell epitopes of the major peanut allergens Ara h 1-3. Objective We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. Methods Measurements of total peanut-specific IgE (psIgE) and psIgG4 were made with CAP-FEIA. We analyzed sera from 22 OIT subjects and 6 controls and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1-3 using a high-throughput peptide microarray technique. Antibody affinity was measured using a competitive peptide microarray as previously described. Results At baseline, psIgE and psIgG4 diversity were similar between subjects and controls, and there was broad variation in epitope recognition. After a median 41 months of OIT, polyclonal psIgG4 increased from a median 0.3 mcg/mL (IQR 0.1-0.43) at baseline to 10.5 mcg/mL (3.95-45.48) (p<0.0001) and included de novo specificities. PsIgE was reduced from a median baseline of 85.45 kUA/L (23.05-101.0) to 7.75 kUA/L (2.58-30.55) (p<0.0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated subjects, several subjects generated new IgE specificities even as the total psIgE decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2. Conclusion OIT differentially alters Ara h 1-3 binding patterns. These changes are variable between subjects, not observed in controls, and include a progressive polyclonal increase in IgG4, with concurrent reduction in IgE amount and diversity. PMID:23199605

  14. Fungal allergens.

    PubMed Central

    Horner, W E; Helbling, A; Salvaggio, J E; Lehrer, S B

    1995-01-01

    Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immunotherapy of allergy to fungi require well-characterized or standardized extracts that contain the relevant allergen(s) of the appropriate fungus. Production of standardized extracts is difficult since fungal extracts are complex mixtures and a variety of fungi are allergenic. Thus, the currently available extracts are largely nonstandardized, even uncharacterized, crude extracts. Recent significant progress in isolating and characterizing relevant fungal allergens is summarized in the present review. Particularly, some allergens from the genera Alternaria, Aspergillus, and Cladosporium are now thoroughly characterized, and allergens from several other genera, including some basidiomycetes, have also been purified. The availability of these extracts will facilitate definitive studies of fungal allergy prevalence and immunotherapy efficacy as well as enhance both the diagnosis and therapy of fungal allergy. PMID:7621398

  15. A naturally occurring hypoallergenic variant of vespid Antigen 5 from Polybia scutellaris venom as a candidate for allergen-specific immunotherapy.

    PubMed

    Vinzón, Sabrina E; Marino-Buslje, Cristina; Rivera, Elena; Biscoglio de Jiménez Bonino, Mirtha

    2012-01-01

    Stings by insects from the Hymenoptera order are known to cause life-threatening allergic reactions and impair life quality. Despite the effectiveness of conventional vespid venom immunotherapy, more standardized and safer allergy vaccines are required and recombinant hypoallergenic variants are important clinical tools. Antigen 5 is a major allergen of vespid venoms and it was previously reported that Antigen 5 from Polybia scutellaris (Poly s 5) could be a hypoallergenic variant. In this work we assess the immunological behavior and allergenic activity of Poly s 5 in order to explore its suitability for specific immunotherapy. With this aim, recombinant Poly s 5 was expressed in Pichia pastoris and the presence of cross-reactive epitopes with Pol a 5, a known allergenic Antigen 5, was investigated both at the IgG and IgE levels, by ELISA assays and a basophil-mediator release assay respectively. A molecular model was also built to better understand the relationship between immunological and structural aspects. In mice, Poly s 5 induced IgG antibodies which cross-reacted with Pol a 5. However, Poly s 5 induced only minimal amounts of IgE and was a poor inducer of basophil-mediator release, even when the cells were sensitized with Pol a 5-specific IgE. Moreover, Poly s 5-specific serum showed a specific protective activity and was able to inhibit the Pol a 5-induced basophil degranulation. Structural analysis from the molecular model revealed that a few amino acid substitutions in the N-terminal region of Poly s 5 should lead to an alteration of the surface topography and electrostatic potential of the epitopes which could be responsible for its hypoallergenic behavior. These findings, taken as a whole, show that Poly s 5 is likely a naturally occurring hypoallergenic Antigen 5 variant. PMID:22844463

  16. Concentrated protein body product derived from rice endosperm as an oral tolerogen for allergen-specific immunotherapy--a new mucosal vaccine formulation against Japanese cedar pollen allergy.

    PubMed

    Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

    2015-01-01

    The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation. PMID:25774686

  17. Allergen structures and epitopes.

    PubMed

    Meno, K H

    2011-07-01

    Human type 1 hypersensitivity diseases such as allergic rhinoconjunctivitis are characterized by allergen-specific IgE antibodies produced in allergic individuals after allergen exposure. IgE antibodies bound to receptors on the surface of effector cells trigger an allergic response by interacting with three-dimensional (conformational) epitopes on the allergen surface. Crystal structures are available for complexes of antibody specifically bound to five allergens, from birch pollen, bee venom, cockroach, cow's milk and timothy grass pollen. The details of the antibody-allergen interaction extending all the way to atomic resolution are available from such complexes. In vitro investigations using recombinant monoclonal antibodies and human basophils show that binding affinity is a key to triggering the allergic response. Continued molecular characterization of antibody-allergen interactions is paving the way for the use of recombinant allergens in allergen-specific diagnosis and immunotherapy. PMID:21668845

  18. Evaluation on the immunotherapy efficacies of synthetic peptide vaccines in asthmatic mice with group I and II allergens from Dermatophagoides pteronyssinus

    PubMed Central

    Li, Chaopin; Xu, Pengfei; Xu, Haifeng; Zhu, Haibin

    2015-01-01

    To assess the immunotherapy efficacies of recombinant vaccines containing T-cell epitopes derived from group I and allergens from Dermatophagoides pteronyssinus (Der p1, Der p2). Forty female BALB/c mice were randomized into groups of negative control (PBS group), positive controls (Asthma group), immunotherapy with rDer p1 and rDer p2 protein suspension (rDer p1/rDer p2 group) and specific immunotherapy with fusion peptide T1-8 (T1-8 group). Asthmatic mouse models were initially established with the crude extract from house dust mites (HDM), and PBS models were solely treated with PBS buffer. The two treatment groups were managed with corresponding protein via subcutaneous injection at the back 30 minutes before inhalation sensitization from day 25 to 27. Twenty-four hour following the final inhalation challenge, sera, bronchoalveolar lavage fluid (BALF) and the supernatant of splenocyte cultures (SSCC) were collected in each group of mice. ELISA was used to assay the levels of IFN-γ, IL-4, IL-10 and IL-17 in the BALF and SSCC, as well as serum levels of specific IgE, IgG1 and IgG2a. The lung tissue sections were stained with haematoxylin and eosin (H&E) for pathological examination. ELISA detection revealed reduced levels of IL-4 and IL-17 in the BALF and SSCC, yet increased levels of IFN-γ and IL-10, and decreased specific serum IgE and IgG1, yet increased serum IgG2a in T1-8 group and rDer p1/rDer p2 group than asthma group (P<0.05). T1-8 group had lower IL-4 and IL-17 level and higher IFN-γ and IL-10 level in the BALF and SSCC as well as reduced specific serum IgE and IgG1, yet elevated IgG2a level compared to rDer p1/rDer p2 group (P<0.05). Examination on the lung sections indicated significantly abated pulmonary inflammation, less inflammatory cell infiltration and better remodeled airway epithelia in T1-8 group and rDer p1/rDer p2 group than asthma group. However, the airway epithelium structure T1-8 group and rDer p1/rDer p2 group remained similar to

  19. Outdoor allergens.

    PubMed Central

    Burge, H A; Rogers, C A

    2000-01-01

    Outdoor allergens are an important part of the exposures that lead to allergic disease. Understanding the role of outdoor allergens requires a knowledge of the nature of outdoor allergen-bearing particles, the distributions of their source, and the nature of the aerosols (particle types, sizes, dynamics of concentrations). Primary sources for outdoor allergens include vascular plants (pollen, fern spores, soy dust), and fungi (spores, hyphae). Nonvascular plants, algae, and arthropods contribute small numbers of allergen-bearing particles. Particles are released from sources into the air by wind, rain, mechanical disturbance, or active discharge mechanisms. Once airborne, they follow the physical laws that apply to all airborne particles. Although some outdoor allergens penetrate indoor spaces, exposure occurs mostly outdoors. Even short-term peak outdoor exposures can be important in eliciting acute symptoms. Monitoring of airborne biological particles is usually by particle impaction and microscopic examination. Centrally located monitoring stations give regional-scale measurements for aeroallergen levels. Evidence for the role of outdoor allergens in allergic rhinitis is strong and is rapidly increasing for a role in asthma. Pollen and fungal spore exposures have both been implicated in acute exacerbations of asthma, and sensitivity to some fungal spores predicts the existence of asthma. Synergism and/or antagonism probably occurs with other outdoor air particles and gases. Control involves avoidance of exposure (staying indoors, preventing entry of outdoor aerosols) as well as immunotherapy, which is effective for pollen but of limited effect for spores. Outdoor allergens have been the subject of only limited studies with respect to the epidemiology of asthma. Much remains to be studied with respect to prevalence patterns, exposure and disease relationships, and control. PMID:10931783

  20. IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human.

    PubMed

    Freiberger, S N; Zehnder, M; Gafvelin, G; Grönlund, H; Kündig, T M; Johansen, P

    2016-09-01

    Allergy immunotherapy (AIT) mediates protection against allergen exposure in part due to allergen-specific antibodies. While immunization typically stimulated IgG1 and IgG2, AIT is often associated with production of IgG4. Here, twenty cat dander-sensitized patients were randomized to receive three injections of intralymphatic immunotherapy (ILIT) with MAT-Feld1 adsorbed to aluminum hydroxide or just aluminum hydroxide (placebo) in a double-blind setting (ClinicalTrials.gov NCT00718679). Whereas the clinical data, showing benefit of Mat-Feld1 ILIT was published in 2012 (Senti et al., J Allergy Clin Immunol, vol 129(5):1290-1296), the current study investigated the cat allergen-specific antibody responses. Blood was drawn prior to ILIT, as well as 1, 3, and 12 months after first ILIT. The sera were analyzed to characterize all IgG subclasses and IgE antibody responses. ILIT with MAT-Feld1 elicited high levels of total IgG that were maintained for at least 12 months. Interestingly, a strong increase in IgG4 and some increase in IgG2 were observed throughout the study, while production of cat-specific IgG1 and IgG3 was not stimulated by MAT-Feld1 ILIT. The IgE levels remained constant. PMID:27253988

  1. Allergens in veterinary medicine

    PubMed Central

    Mueller, R. S.; Janda, J.; Jensen-Jarolim, E.; Rhyner, C.; Marti, E.

    2015-01-01

    Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses. PMID:26280544

  2. Allergens in veterinary medicine.

    PubMed

    Mueller, R S; Janda, J; Jensen-Jarolim, E; Rhyner, C; Marti, E

    2016-01-01

    Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses. PMID:26280544

  3. Evaluation of stability of allergen extracts for sublingual immunotherapy during transport under unfavourable temperature conditions with an innovative thermal insulating packaging.

    PubMed

    Puccinelli, P; Natoli, V; Dell'albani, I; Scurati, S; Incorvaia, C; Barbieri, S; Masieri, S; Frati, F

    2013-01-01

    Many pharmaceutical and biotechnological products are temperature-sensitive and should normally be kept at a controlled temperature, particularly during transport, in order to prevent the loss of their stability and activity. Therefore, stability studies should be performed for temperature-sensitive products, considering product characteristics, typical environmental conditions, and anticipating environmental extremes that may occur during product transport in a specific country. Staloral products for sublingual immunotherapy are temperature sensitive and are labelled for maintenance under refrigerated conditions (2-8°C). Given the peculiar climatic context of Italy and the great temperature fluctuations that may occur during transport, this study was aimed at evaluating the impact of a new engineered thermal insulating packaging for Staloral. In particular, the purpose was to assess whether the new packaging could create a container condition able to preserve the stability and immunological activity of the product during the transport phase throughout Italy. The results showed that the range of temperatures that can affect the product, in the area surrounding the product packaging, may reach a peak of 63°C during transport under the most unfavourable climatic conditions, i.e. in a non-refrigerated van during the summer season, from the site of production in France to the patient's house in Catania, the city with the highest temperatures in Italy. However, the highest temperature reached inside the vaccine did not exceed 45°C over a period of about 2 h. The ELISA inhibition test on samples subjected to the extreme temperature conditions previously defined (45°C) showed an immunological activity higher than 75% of that initially measured and was comparable to those obtained with samples stored at controlled temperature (5°C). This means that, even in the worst case scenario, the structure of the allergen extracts is not influenced and the vaccine potency is

  4. Immunotherapy: first do no harm.

    PubMed

    Moss, Mark H

    2005-05-01

    Immunotherapy continues to be a treatment modality that is used most exclusively by allergists. The acceptance of immunotherapy for treating children with allergic rhinitis or asthma has been limited by the lack of adequate numbers of pediatric double-blind, placebo-controlled trials of specific allergen immunotherapy; use of venom immunotherapy is more clearly supported by current data. Children represent a unique group of patients where allergic disease may not only be treated using immunotherapy resulting in reduction of symptoms, signs, and complications of disease, but may also hold the best potential for the evasive goal of prevention of the development of future allergic disease. PMID:15878464

  5. Conference Scene: novelties in immunotherapy.

    PubMed

    Mitsias, Dimitris I; Kalogiros, Lampros A; Papadopoulos, Nikolaos G

    2013-10-01

    The only method aiming to permanently cure allergic disorders is allergen immunotherapy. Over the last 20 years there has been great progress in understanding the mechanisms that govern allergen immunotherapy in order to meet three basic prerequisites: safety, effectiveness and compliance. In the present summary report from the European Academy of Allergology and Clinical Immunology-World Allergy Organization Congress held last June in Milan, we review key points concerning the main axes as diagnosis, novel modalities, routes and protocols, as well as two important immunotherapy fields: food and insect venom allergy. PMID:24088073

  6. Assessment of Instructional Terms (AIT).

    ERIC Educational Resources Information Center

    Alparaque, Idrenne; Fagan, William T.

    Designed to grade children's knowledge of commonly used instructional terms in a particular language arts program, the AIT consists of a verbal part and a situational part. Each part assesses the same commonly used instructional terms: word, begin, letter, name, makes sense, beginning sounds, print, trace, capital letter, rhyme, period, stands…

  7. Allergen nomenclature*

    PubMed Central

    1994-01-01

    The revised nomenclature for allergens is presented together with proposed nomenclatures for (a) allergen genes, mRNAs and cDNAs, and (b) recombinant and synthetic peptides of allergenic interest. PMID:7955031

  8. House dust allergy and immunotherapy

    PubMed Central

    Thomas, Wayne R.

    2012-01-01

    HDM allergy is associated with asthma, allergic rhinitis and atopic dermatitis. In many countries childhood asthma is predominantly found in HDM-allergic children with their probability of developing disease being proportional to their IgE antibody titers and the early development of Th2 responses. While the pathogenesis is complex and increasingly linked to infection the immunologically-based allergen immunotherapy and anti-IgE antibody therapy are highly beneficial. Immunotherapy could be a short-term treatment providing lifelong relief but the current regimens depend on repeated administration of allergen over years. Immunological investigations point to a contribution of responses outside the Th2 pathway and multiple potential but unproven control mechanisms. Over half of the IgE antibodies are directed to the group 1 and 2 allergens with most of remainder to the group 4, 5, 7 and 21 allergens. This hierarchy found in high and low responders provides a platform for introducing defined allergens into immunotherapy and defined reagents for investigation. PMID:22894952

  9. Allergen nomenclature.

    PubMed Central

    Marsh, D. G.; Goodfriend, L.; King, T. P.; Lowenstein, H.; Platts-Mills, T. A.

    1986-01-01

    This article presents a nomenclature system for allergens which has been officially recommended by the International Union of Immunological Societies (IUIS). The nomenclature is based on proposals of the IUIS Sub-Committee for Allergen Nomenclature and is applicable to highly purified, well-characterized allergens and to non-purified or partially purified allergenic extracts. PMID:3492310

  10. New insights into ragweed pollen allergens.

    PubMed

    Bordas-Le Floch, Véronique; Groeme, Rachel; Chabre, Henri; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent; Moingeon, Philippe

    2015-11-01

    Pollen allergens from short ragweed (Ambrosia artemisiifolia) cause severe respiratory allergies in North America and Europe. To date, ten short ragweed pollen allergens belonging to eight protein families, including the recently discovered novel major allergen Amb a 11, have been recorded in the International Union of Immunological Societies (IUIS) allergen database. With evidence that other components may further contribute to short ragweed pollen allergenicity, a better understanding of the allergen repertoire is a requisite for the design of proper diagnostic tools and efficient immunotherapies. This review provides an update on both known as well as novel candidate allergens from short ragweed pollen, identified through a comprehensive characterization of the ragweed pollen transcriptome and proteome. PMID:26383916

  11. Local and systemic immunotherapy in nasal allergy.

    PubMed

    Palma-Carlos, A G; Palma-Carlos, M L; Spínola Santos, A; Santos, C; Pedro, E; Pregal, A

    1999-10-01

    Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity. PMID:10577807

  12. Pollen Allergens for Molecular Diagnosis.

    PubMed

    Pablos, Isabel; Wildner, Sabrina; Asam, Claudia; Wallner, Michael; Gadermaier, Gabriele

    2016-04-01

    Pollen allergens are one of the main causes of type I allergies affecting up to 30 % of the population in industrialized countries. Climatic changes affect the duration and intensity of pollen seasons and may together with pollution contribute to increased incidences of respiratory allergy and asthma. Allergenic grasses, trees, and weeds often present similar habitats and flowering periods compromising clinical anamnesis. Molecule-based approaches enable distinction between genuine sensitization and clinically mostly irrelevant IgE cross-reactivity due to, e. g., panallergens or carbohydrate determinants. In addition, sensitivity as well as specificity can be improved and lead to identification of the primary sensitizing source which is particularly beneficial regarding polysensitized patients. This review gives an overview on relevant pollen allergens and their usefulness in daily practice. Appropriate allergy diagnosis is directly influencing decisions for therapeutic interventions, and thus, reliable biomarkers are pivotal when considering allergen immunotherapy in the context of precision medicine. PMID:27002515

  13. Mechanisms of immunotherapy to aeroallergens.

    PubMed

    Shamji, M H; Durham, S R

    2011-09-01

    Allergen immunotherapy is allergen-specific, allergen dose- and time-dependent and is associated with long-term clinical and immunological tolerance that persists for years after discontinuation. Successful immunotherapy is accompanied by the suppression of numbers of T-helper 2 (Th2) effector cells, eosinophils, basophils, c-kit+mast cells and neutrophils infiltration in target organs, induction of IL-10 and/or TGF-β+Treg cells and increases in 'protective' non-inflammatory blocking antibodies, particularly IgG4 and IgA2 subclasses with inhibitory activity. These events are accompanied by a reduction and/or a redirection of underlying antigen-specific Th2-type T cell-driven hypersensitivity to the allergen(s) used for therapy. This suppression occurs within weeks or months as a consequence of the appearance of a population of regulatory T cells that exert their effects by mechanisms involving cell-cell contact, but also by the release of cytokines such as IL-10 (increases IgG4) and TGF-β (increases specific IgA). The more delayed-in-time appearance of antigen-specific T-helper 1 responses and alternative mechanisms such as Th2 cell anergy and/or apoptosis may also be involved. The mechanisms of sublingual immunotherapy are similar to those following a subcutaneous administration of allergen, whereas it is likely that additional events following antigen presentation in the sublingual mucosa and regional lymph nodes are involved. These insights have resulted in novel approaches and portend future biomarkers that may be surrogate or predictive of the clinical response to treatment. PMID:21762223

  14. The future of sublingual immunotherapy.

    PubMed

    Marcucci, F; Duse, M; Frati, F; Incorvaia, C; Marseglia, G L; La Rosa, M

    2009-01-01

    Sublingual immunotherapy (SLIT) is currently the most prescribed form of allergen immunotherapy in many European countries. Its use has been accepted in the international consensus publications, and recently also the scepticism of USA scientists is attenuated. Still, this treatment may be improved, and the possible developments consist of modification of the materials, use of adjuvants and use of recombinant allergens. Moreover, new applications of SLIT, such as food allergy, seem promising. Concerning materials, the future form of SLIT is likely to be represented by tablets, which were already tested for efficacy and safety with grass pollen extracts, and are likely to increase the convenience for the patient by the use of no-updosing schedule. Adjuvants fitting with the characteristics of SLIT seem to be CpG oligodeoxynucleotides (CpG), able to interact with the Toll-like receptor 9 (TLR9) whose activation induces a Th1-like pattern of cytokine release, combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3-Dex), and Lactobacillus plantarum. The approach with recombinant allergens, named component-resolved diagnosis, offers the possibility to tailor immunotherapy, which was found to be effective in two randomized trials of subcutaneous SIT (16-17), while studies with SLIT are not yet available. Regarding food allergy, an important controlled study demonstrated that SLIT with hazelnut is able to increase patients tolerance over possible reactions from inadvertent assumption of the culprit food, and warrants for further trials with other foods. PMID:19944008

  15. Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy

    PubMed Central

    Li, Lisha

    2016-01-01

    Background Although many patients with allergic rhinitis have symptoms due to sensitization to more than one kind of allergens, and mixed allergen extracts are widely used for immunotherapy, there are few published trials. Objective Our study aimed to evaluate the effect of multiple-allergen immunotherapy on improving the symptoms and quality of life of allergic rhinitis patients. Methods We performed a 1-year single-center observation study of subcutaneous immunotherapy using house dust mite extract (n = 12), weed pollen extract (n = 21), or mixed house dust mite/weed pollen extract (n = 11) in 44 allergic rhinitis patients. All the allergens responsible for the symptom of each patient were included in his immunotherapy. Symptom score, medication score, and quality of life of the patients were evaluated before and after 1-year immunotherapy. Quality of life was evaluated with the Rhinoconjunctivitis Quality of Life Questionnaire. Results In all 3 groups receiving subcutaneous immunotherapy, significant improvement of symptom score, medication score, and quality of life was found vs. baseline at 1 year, irrespective of the allergen used. In the weed pollen season, the changes of quality of life questionnaire score after 1-year treatment were not significantly different between the weed pollen group (1.55 ± 1.24) and the mixed house dust mite/weed pollen group (1.14 ± 1.01). The same happened in the nonpollen seasons, during which dust mite immunotherapy (1.23 ± 1.63) and mixed immunotherapy (0.60 ± 0.47) did not show significantly different effect on the quality of life. Conclusion The multiple-allergen immunotherapy might be effective in polysensitized allergic rhinitis patients, and could improve their quality of life. Our result did not show significant difference between the effects of multiple-allergen immunotherapy and mono-allergen immunotherapy. PMID:27489789

  16. Mammalian-derived respiratory allergens - implications for diagnosis and therapy of individuals allergic to furry animals.

    PubMed

    Nilsson, Ola B; van Hage, Marianne; Grönlund, Hans

    2014-03-01

    Furry animals cause respiratory allergies in a significant proportion of the population. A majority of all mammalian allergens are spread as airborne particles, and several have been detected in environments where furry animals are not normally kept. The repertoire of allergens from each source belongs to a restricted number of allergen families. Classification of allergen families is particularly important for the characterization of allergenicity and cross-reactivity of allergens. In fact, major mammalian allergens are taken from only three protein families, i.e. the secretoglobin, lipocalin and kallikrein families. In particular, the lipocalin superfamily harbours major allergens in all important mammalian allergen sources, and cross-reactivity between lipocalin allergens may explain cross-species sensitization between mammals. The identification of single allergen components is of importance to improve diagnosis and therapy of allergic patients using component-resolved diagnostics and allergen-specific immunotherapy (ASIT) respectively. Major disadvantages with crude allergen extracts for these applications emphasize the benefits of careful characterization of individual allergens. Furthermore, detailed knowledge of the characteristics of an allergen is crucial to formulate attenuated allergy vaccines, e.g. hypoallergens. The diverse repertoires of individual allergens from different mammalian species influence the diagnostic potential and clinical efficacy of ASIT to furry animals. As such, detailed knowledge of individual allergens is essential for adequate clinical evaluation. This review compiles current knowledge of the allergen families of mammalian species, and discusses how this information may be used for improved diagnosis and therapy of individuals allergic to mammals. PMID:24041755

  17. Novel developments in the mechanisms of immune tolerance to allergens.

    PubMed

    Eiwegger, Thomas; Gruber, Saskia; Szépfalusi, Zsolt; Akdis, Cezmi A

    2012-10-01

    Allergy is the result of a disbalanced immune response to environmental innocuous antigens. Despite of accumulating data to define the pathomechanisms that take place in case of allergic diseases a detailed understanding of sequence of events that lead to the "normal" scenario of tolerance development are still under debate. Allergen-specific immunotherapy is the only causal treatment of allergic diseases. It modifies the immune response to a particular antigen to achieve tolerance against the symptom-causing allergen. This process is considered to mirror physiological peripheral tolerance induction. A number of immunological changes have been described to occur under allergen immunotherapy, including the generation of allergen-specific regulatory T cells, the induction of allergen-specific IgG4, an increase in the Th1/Th2 cytokine ratio and decreased activation and function of effector cells such as mast cells, basophils and eosinophils. PMID:23095863

  18. Tamazight Basic Course: Ait Mgild Dialect.

    ERIC Educational Resources Information Center

    Harries, Jeanette

    The materials for this course in the Ait Mgild dialect of Tamazight, one of the three main languages into which the Berber dialects of Morocco are grouped, include this textbook, 32 tape recordings, and 260 colored slides keyed to the lessons. Lesson material on each tape does not exceed 26 minutes. The remaining four to eight minutes of the tape…

  19. NOVEL IMMUNOTHERAPIES

    PubMed Central

    Yi, Qing

    2010-01-01

    Multiple myeloma is still a fatal disease. Despite advances in high-dose chemotherapy, stem cell transplantation, and the development of novel therapeutics, relapse of the underlying disease remains the primary cause of treatment failure. Strategies for post-transplantation immunomodulation are desirable for eradication of remaining tumor cells. To this end, immunotherapy aimed at inducing myeloma-specific immunity in patients has been explored. Idiotype protein, secreted by myeloma cells, has been the primary target for immunotherapy as it is the best defined tumor-specific antigen. This chapter focuses on novel immunotherapies that are being developed to treat patients with myeloma. I will discuss potential myeloma antigens, antigen-specific T cells and their function on myeloma tumor cells, and T-cell-based and antibody-based immunotherapies for myeloma. Furthermore, clinical studies of T-cell-based immunotherapy in the form of vaccination, allogeneic stem cell transplantation and donor lymphocyte infusions, with or without donor vaccination using patient-derived idiotype, and future application of donor-derived or patient-derived, antigen-specific T-cell infusion in this disease are also discussed. Based on the specificity of the immune effector molecules and cells, immunotherapies with specific T cells or therapeutic antibodies may represent novel strategies for the treatment of multiple myeloma in the near future. PMID:20010170

  20. A practical view of immunotherapy for food allergy

    PubMed Central

    2016-01-01

    Food allergy is common and sometimes life threatening for Korean children. The current standard treatment of allergen avoidance and self-injectable epinephrine does not change the natural course of food allergy. Recently, oral, sublingual, and epicutaneous immunotherapies have been studied for their effectiveness against food allergy. While various rates of desensitization (36% to 100%) and tolerance (28% to 75%) have been induced by immunotherapies for food allergy, no single established protocol has been shown to be both effective and safe. In some studies, immunologic changes after immunotherapy for food allergy have been revealed. Adverse reactions to these immunotherapies have usually been localized, but severe systemic reactions have been observed in some cases. Although immunotherapy cannot be recommended for routine practice yet, results from recent studies demonstrate that immunotherapies are promising for the treatment of food allergy. PMID:26958062

  1. Immunotherapy as a disease modifier.

    PubMed

    Martin, James G; Shalaby, Karim; Michoud, Marie-Claire

    2006-01-01

    Immunotherapy was formerly the treatment of allergic disease by repeated exposure to allergen. Other approaches to immune modulation have emerged using new knowledge of T cell function. The so-called hygiene hypothesis argues that alterations in our environment have resulted in a failure of the immune system to develop normally, such that excessive Th2 type responses to antigen exposures occur. These observations have prompted therapies designed to promote a shift from Th-2 to Th-1 responses. These therapies include bacterial vaccines and stimulation of the immune system with Toll like receptor ligands or bacterial nucleotide immunostimulatory sequences (CpG motifs). Traditional desensitization immunotherapy is being re-examined and anti-IgE therapy is also enjoying a measure of success. PMID:16798526

  2. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives

    PubMed Central

    Linhart, Birgit; Valenta, Rudolf

    2015-01-01

    Hundred years ago therapeutic vaccination with allergen-containing extracts has been introduced as a clinically effective, disease-modifying, allergen-specific and long-lasting form of therapy for allergy, a hypersensitivity disease affecting more than 25% of the population. Today, the structures of most of the disease-causing allergens have been elucidated and recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during allergen-specific immunotherapy (SIT). These recombinant hypoallergens have been characterized in vitro, in experimental animal models and in clinical trials in allergic patients. This review provides a summary of the molecular, immunological and preclinical evaluation criteria applied for this new generation of allergy vaccines. Furthermore, we summarize the mechanisms underlying SIT with recombinant hypoallergens which are thought to be responsible for their therapeutic effect. PMID:22100888

  3. Oral immunotherapy for food allergy.

    PubMed

    Tang, Mimi L K

    2009-01-01

    Current management of food allergy involves strict avoidance, education on recognizing and managing allergic reactions, and carrying an adrenaline autoinjector. This approach is burdensome and associated with reduced quality of life. Patients with food allergy would benefit greatly from a treatment that could achieve desensitization or long-term tolerance. Recent studies have shown that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses; however, it remains uncertain whether OIT can induce long-term tolerance. Nevertheless, successful desensitization provides a major advance in management by reducing the risk of reaction to low amounts of allergen. Allergic reactions during OIT are common, although severe reactions are less common. Therefore, OIT should be performed in specialist centers under close medical supervision and would ideally be conducted as part of ongoing research studies. OIT holds promise as a novel approach to managing food allergy. PMID:19063824

  4. Oral Immunotherapy for Food Allergies.

    PubMed

    Feuille, Elizabeth; Nowak-Węgrzyn, Anna

    2016-01-01

    Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice. PMID:27355816

  5. Management of polysensitized patient: from molecular diagnostics to biomolecular immunotherapy.

    PubMed

    Ciprandi, Giorgio; Incorvaia, Cristoforo; Frati, Franco

    2015-01-01

    A panel of Italian allergists gathered to discuss the issue concerning the management of polysensitized patients. The main conclusions were as follows: polysensitization is a relevant clinical characteristic as it affects about 70-80% of the global allergic population; the diagnostic pathway needs the use of an adequate and thorough methodology, based on the demonstration of consistency between history and documented sensitization; polysensitization and polyallergy are not synonymous: true allergy should always be demonstrated; polysensitization does not constitute a limitation to allergen immunotherapy prescription, as 1-2 allergen extracts could be effective in polysensitized patients; the allergen immunotherapy product characteristics should include the following: high efficacy and optimal safety profile, standardized production, and documented presence and titration of the major allergen. PMID:26144241

  6. [Scleroderma related to specific immunotherapy. A report of a case].

    PubMed

    Morfín Maciel, Blanca María; Castillo Morfín, Blanca María

    2009-01-01

    It has been described two main phenotypes of helper T cells. On activation, the immune system develops the most effective Th response. Whereas Th1 cells promote cell-mediate immunity against intracellular pathogens and an over expression could favor autoimmune diseases; Th2 cells develop humoral immunity against extracellular pathogens promoting allergic response. Normally, the two profiles coexist in the same individual with different grades of expression. Recently, it has been described a new subset: Th17, which is related to tissue injury in autoimmune diseases. Then, allergic and autoimmune diseases result from an unbalanced response of the immune system. Allergen-specific immunotherapy is the only curative treatment of a specific allergy, which leads to a life-long tolerance against allergens. There are no controlled studies about the effectiveness or risks associated with allergen-specific immunotherapy in patients with autoimmune disorders. On the other hand, scleroderma is an autoimmune chronic systemic disorder of unknown etiology characterized by excess collagen deposition in the skin and viscera, along with vascular injury. We report a girl with allergic asthma and with a second degree family history of systemic sclerosis who developed localized scleroderma during allergen specific immunotherapy. Because allergy vaccination alter the balance between effector and regulatory T-cell populations, which regulate immune tolerance, a positive family history of autoimmunity in first or second degree, could be a contraindication for allergen-specific immunotherapy. PMID:19768975

  7. Advances in the Treatment of Food Allergy: Sublingual and Epicutaneous Immunotherapy.

    PubMed

    Sindher, Sayantani; Fleischer, David M; Spergel, Jonathan M

    2016-02-01

    Food allergies continue to increase in prevalence. Standard care is a strict elimination diet, but life-threatening reactions still occur. Allergen immunotherapy has the most potential in treating food allergy. Subcutaneous immunotherapy has not been adopted into food allergy therapy. Oral immunotherapy has a high rate of adverse reactions. Sublingual immunotherapy (SLIT) uses the tolerogenic environment of the oral mucosa and epicutaneous immunotherapy (EPIT) uses the immune cells of the epidermis to transport antigens to afferent lymph nodes to activate immune responses. SLIT and EPIT can successfully desensitize patients. More research is needed to define optimal doses and administration protocols. PMID:26617226

  8. Peanut allergens.

    PubMed

    Becker, Wolf-Meinhard; Jappe, Uta

    2014-01-01

    The earliest known evidence of peanut farming dates back 7,600 years. With a prevalence of roughly 1%, peanut allergy is a diagnostic and treatment challenge, but is also a very good model for studying all aspects of food allergy, including its molecular basis and pathomechanisms. Therefore, the very starting point for elucidating all these aspects is the identification of peanut allergens with subsequent clearing of their structure and their preparation as pure recombinant and/or natural allergens. This is the basis for in vitro diagnostic tests as well as the development of immunotherapeutic drugs. With regard to class I food allergy, peanut allergy affects by far the largest group of patients. In peanuts, 12 allergens have been identified and their molecular characteristics are described herein. Ara h 1, Ara h 3.01 and Ara h 3.02 (the former Ara h 4) belong to the cupin superfamily. The conglutins Ara h 2, Ara h 6 and Ara h 7, and the non-specific lipid transfer protein Ara h 9 belong to the prolamin superfamily. Ara h 5 (profilin) and Ara h 8 (Bet v 1-homologous protein) cause class II food allergies and are associated with inhalation allergy to pollen via the sequential and/or conformational similarity of molecules. Two peanut oleosins are listed as Ara h 10 and Ara h 11 and two defensins as Ara h 12 and Ara h 13 by the WHO/IUIS Allergen Nomenclature Subcommittee. The effect of the above-specified allergens has to be considered in the context of their matrix, which is influenced by processing factors and the individual's immune system. PMID:24925406

  9. Strategies for recombinant allergen vaccines and fruitful results from first clinical studies.

    PubMed

    Cromwell, Oliver; Fiebig, Helmut; Suck, Roland; Kahlert, Helga; Nandy, Andreas; Kettner, Jens; Narkus, Annemie

    2006-05-01

    Recombinant DNA technology has delivered the prospect of a new generation of preparations for allergen-specific immunotherapy. The first clinical studies with recombinant allergens have yielded encouraging results, suggesting that there is a good chance that such preparations will become available for use in the routine management of allergic disease. PMID:16701144

  10. Relevance of a 5-grass sublingual tablet for immunotherapy of patients with grass pollen allergy in North America.

    PubMed

    Moingeon, Philippe; Cox, Linda

    2016-06-01

    Grass pollen allergy is common and clinically consequential in North America. While it is frequently treated with subcutaneous or sublingual immunotherapy, debate remains regarding whether allergen immunotherapy is best carried out using a single representative or multiple cross-reactive allergen(s). Patients are commonly exposed to pollens from multiple allergenic grass species belonging to the Pooideæ subfamily. Beyond the known IgE cross-reactivity, considerable molecular heterogeneity exists with respect to allergen content among grass species, with further evidence that these molecular variants can be detected by the patients' immune system. These observations provide a compelling scientific rationale for the use of mixed pollen allergen extracts to broaden the allergen repertoire, with the aim of reorienting inappropriate immune responses in allergic patients. PMID:26813047

  11. Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges.

    PubMed

    Han, Ethan Q; Li, Xiu-ling; Wang, Chun-rong; Li, Tian-fang; Han, Shuang-yin

    2013-01-01

    Recent years have witnessed much progress in both basic research and clinical trials regarding cancer immunotherapy with chimeric antigen receptor (CAR)-engineered T cells. The unique structure of CAR endows T cell tumor specific cytotoxicity and resistance to immunosuppressive microenvironment in cancers, which helps patients to better tackle the issue of immunological tolerance. Adoptive immunotherapy (AIT) using this supernatural T cell have gained momentum after decades of intense debates because of the promising results obtained from preclinical models and clinical trials. However, it is very important for us to evaluate thoroughly the challenges/obstacles before widespread clinical application, which clearly warrants more studies to improve our understanding of the mechanism underlying AIT. In this review, we focus on the critical issues related to the clinical outcomes of CAR-based adoptive immunotherapy and discuss the rationales to refine this new cancer therapeutic modality. PMID:23829929

  12. [Allergen analysis].

    PubMed

    Röder, Martin; Weber, Wolfgang

    2016-07-01

    The fundamental requirement when testing for and ensuring compliance with legally required labelling regulations is the reliable analysis of food allergens. This can be carried out by means of either DNA (deoxyribonucleic acid) or protein detection. Protein detection has the advantage of directly detecting the allergenic component and can currently be carried out using immunological (enzyme-linked immunosorbent assay [ELISA])/lateral flow devices [LFD]) or mass spectrometry-based techniques. DNA detection is indirect, but allows the presence of food allergens to be validated through the use of another marker. Each method has its pros and cons, which have to be considered on a case-by-case basis. ELISA is quantitative, quick and easy to carry out and has high sensitivity. LFD testing is ideal for industrial applications, as the tests can be carried out on-site. Both antibody-based tests may have problems with processed foods and false positive results. Mass-spectrometric techniques show a lot of promise, but are currently still time-consuming and complex to carry out. They also run into problems with processed foods and their degree of sensitivity is matrix and parameter dependent. For these reasons, this technique is only occasionally used. Polymerase chain reaction (PCR) provides the highest specificity and, depending on the target sequence, a very good to good level of sensitivity. Despite the high stability of DNA, PCR is still subject to the influence of processing and matrix related factors. Due to natural variation and production-related changes in the structures relevant in the process of detection, all methods exhibit a relatively high level of uncertainty of measurement. At present, there is no method which provides the absolute correct quantification. However, by means of laboratory-based analyses it is possible to calibrate for the allergen in question and thus be able to make reliable measurements using methods that are already available. PMID

  13. Peanut immunotherapy

    PubMed Central

    2014-01-01

    Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies, such as egg and milk. Peanut allergy has a significant effect on the quality of life of sufferers and their families, due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication, but a disease- modifying therapy is needed for peanut allergy. Recent developments involve the use of immunotherapy, which has shown promise as an active form of treatment. Various routes of administration are being investigated, including subcutaneous, oral, sublingual and epicutaneous routes. Other forms of treatment, such as the use of vaccines and anti-IgE molecules, are also under investigation. So far, results from immunotherapy studies have shown good efficacy in achieving desensitisation to peanut with a good safety profile. However, the issue of long-term tolerance has not been fully addressed yet and larger, phase III studies are required to further investigate safety and efficacy. An assessment of cost/benefit ratio is also required prior to implementing this form of treatment. The use of immunotherapy for peanut allergy is not currently recommended for routine clinical use and should not be attempted outside specialist allergy units. PMID:25276342

  14. Galileo - The Serial-Production AIT Challenge

    NASA Technical Reports Server (NTRS)

    Ragnit, Ulrike; Brunner, Otto

    2008-01-01

    The Galileo Project is one of the most demanding projects of ESA, being Europe's autarkic navigation system and a constellation composed of 30 satellites. This presentation points out the different phases of the project up to the full operational capability and the corresponding launch options with respect to launch vehicles as well as launch configurations. One of the biggest challenges is to set up a small serial 'production line' for the overall integration and test campaign of satellites. This production line demands an optimization of all relevant tasks, taking into account also backup and recovery actions. A comprehensive AIT concept is required, reflecting a tightly merged facility layout and work flow design. In addition a common data management system is needed to handle all spacecraft related documentation and to have a direct input-out flow for all activities, phases and positions at the same time. Process optimization is a well known field of engineering in all small high tech production lines, nevertheless serial production of satellites are still not the daily task in space business and therefore new concepts have to be put in place. Therefore, and in order to meet the satellites overall system optimization, a thorough interface between unit/subsystem manufacturing and satellite AIT must be realized to ensure a smooth flow and to avoid any process interruption, which would directly lead to a schedule impact.

  15. Mold Allergens in Respiratory Allergy: From Structure to Therapy

    PubMed Central

    Twaroch, Teresa E; Curin, Mirela; Swoboda, Ines

    2015-01-01

    Allergic reactions to fungi were described 300 years ago, but the importance of allergy to fungi has been underestimated for a long time. Allergens from fungi mainly cause respiratory and skin symptoms in sensitized patients. In this review, we will focus on fungi and fungal allergens involved in respiratory forms of allergy, such as allergic rhinitis and asthma. Fungi can act as indoor and outdoor respiratory allergen sources, and depending on climate conditions, the rates of sensitization in individuals attending allergy clinics range from 5% to 20%. Due to the poor quality of natural fungal allergen extracts, diagnosis of fungal allergy is hampered, and allergen-specific immunotherapy is rarely given. Several factors are responsible for the poor quality of natural fungal extracts, among which the influence of culture conditions on allergen contents. However, molecular cloning techniques have allowed us to isolate DNAs coding for fungal allergens and to produce a continuously growing panel of recombinant allergens for the diagnosis of fungal allergy. Moreover, technologies are now available for the preparation of recombinant and synthetic fungal allergen derivatives which can be used to develop safe vaccines for the treatment of fungal allergy. PMID:25840710

  16. Wind-pollination and the roles of pollen allergenic proteins.

    PubMed

    Songnuan, Wisuwat

    2013-12-01

    Over the past few decades, there has been an explosion of understanding of the molecular nature of major allergens contained within pollens from the most important allergenic plant species. Most major allergens belong to only a few protein families. Protein characteristics, cross-reactivity, structures, and IgE binding epitopes have been determined for several allergens. These efforts have led to significant improvements in specific immunotherapy, yet there has been little discussion about the physiological functions of these proteins. Even with large amounts of available information about allergenic proteins from pollens, the incidence of pollen allergy continuously increases worldwide. The reason for this increase is unclear and is most likely due to a combination of factors. One important culprit might be a change in the pollen itself. Knowledge about pollen biology and how pollen is changing as a result of more extreme environmental conditions might improve our understanding of the disease. This review focuses on the characteristics of plants producing allergenic pollens that are relevant to pollen allergy, including the phylogenetic relationships, pollen dispersal distances, amounts of pollen produced, amounts of protein in each type of pollen, and how allergenic proteins are released from pollens. In addition, the physiological roles of major allergenic protein families will be discussed to help us understand why some of these proteins become allergens and why GMO plants with hypoallergenic pollens may not be successful. PMID:24383968

  17. Mold allergens in respiratory allergy: from structure to therapy.

    PubMed

    Twaroch, Teresa E; Curin, Mirela; Valenta, Rudolf; Swoboda, Ines

    2015-05-01

    Allergic reactions to fungi were described 300 years ago, but the importance of allergy to fungi has been underestimated for a long time. Allergens from fungi mainly cause respiratory and skin symptoms in sensitized patients. In this review, we will focus on fungi and fungal allergens involved in respiratory forms of allergy, such as allergic rhinitis and asthma. Fungi can act as indoor and outdoor respiratory allergen sources, and depending on climate conditions, the rates of sensitization in individuals attending allergy clinics range from 5% to 20%. Due to the poor quality of natural fungal allergen extracts, diagnosis of fungal allergy is hampered, and allergen-specific immunotherapy is rarely given. Several factors are responsible for the poor quality of natural fungal extracts, among which the influence of culture conditions on allergen contents. However, molecular cloning techniques have allowed us to isolate DNAs coding for fungal allergens and to produce a continuously growing panel of recombinant allergens for the diagnosis of fungal allergy. Moreover, technologies are now available for the preparation of recombinant and synthetic fungal allergen derivatives which can be used to develop safe vaccines for the treatment of fungal allergy. PMID:25840710

  18. Update on Allergy Immunotherapy

    PubMed Central

    2005-01-01

    This article summarizes and provides commentary regarding guidelines on the administration of immunotherapy (IT) for allergic airway disease. Recent investigations have provided important insights into the immunologic mechanism of IT and the prominent role of interleukin-10-producing regulatory T lymphocytes. The most important aspect of successful IT is the administration of an appropriate dose of an extract containing a sufficient concentration of the relevant allergen. This is largely possible now only with standardized extracts. When the major allergen content of successful IT extracts was quantified, efficacy was demonstrated across a surprisingly narrow concentration range (approximately 5-24 μg per injection), irrespective of the extract. This presumably reflects the concentration of an antigen that drives an immune response toward tolerance. It may be predicted that as major allergen content is quantified in currently nonstandardized extracts, effective IT will also be achieved by administering a dose in this range, in contrast to current practices involving fairly arbitrary dosing decisions. With the availability of nonsedating antihistamines, intranasal corticosteroids, and the leukotriene modifiers, inadequate pharmacologic response or intolerable side effects are less commonly the major indications for starting IT for allergic rhinitis (AR). However, with the recognition that a relatively short course (3-5 years) of IT can provide long-term immunomodulation and clinical benefit, a desire to avoid long-term pharmacotherapy and the associated high costs may be the primary indication for IT in AR cases. While evidence overwhelmingly supports the beneficial influences of IT in asthma cases, the positioning of IT for this disorder is not established. The observed prevention of asthma in children who have AR is intriguing, but further studies are required to assess the extent to which the prevalence and severity of chronic asthma will be reduced when these

  19. Facing Hymenoptera Venom Allergy: From Natural to Recombinant Allergens

    PubMed Central

    Perez-Riverol, Amilcar; Justo-Jacomini, Débora Lais; Zollner, Ricardo de Lima; Brochetto-Braga, Márcia Regina

    2015-01-01

    Along with food and drug allergic reactions, a Hymenoptera insect Sting (Apoidea, Vespidae, Formicidae) is one of the most common causes of anaphylaxis worldwide. Diagnoses of Hymenoptera venom allergy (HVA) and specific immunotherapy (SIT) have been based on the use of crude venom extracts. However, the incidence of cross-reactivity and low levels of sensibility during diagnosis, as well as the occurrence of nonspecific sensitization and undesired side effects during SIT, encourage the search for novel allergenic materials. Recombinant allergens are an interesting approach to improve allergy diagnosis and SIT because they circumvent major problems associated with the use of crude venom. Production of recombinant allergens depends on the profound molecular characterization of the natural counterpart by combining some “omics” approaches with high-throughput screening techniques and the selection of an appropriate system for heterologous expression. To date, several clinically relevant allergens and novel venom toxins have been identified, cloned and characterized, enabling a better understanding of the whole allergenic and envenoming processes. Here, we review recent findings on identification, molecular characterization and recombinant expression of Hymenoptera venom allergens and on the evaluation of these heterologous proteins as valuable tools for tackling remaining pitfalls on HVA diagnosis and immunotherapy. PMID:26184309

  20. [Allergen management in the food industry].

    PubMed

    Röder, Martin; Weber, Wolfgang

    2016-07-01

    Due to the lack of causative immunotherapies, individuals with food allergies have to rely on correct labelling for even minute amounts of allergenic constituents. It is not relevant to the allergic whether the source of the culprit food is an ingredient or an allergen that entered the food unintentionally, as is the case with so-called cross-contacts or hidden allergens.Efficient allergen management is the manufacturer's prerequisite for coping with allergenic foods in the food production environment and handling them in a way that avoids cross-contact. If it is technically not feasible to eliminate cross-contacts entirely, it must be ensured that these cross-contacts do not enter the final product without being detected.This article discusses measures that should be considered in allergen management. Examples include recording all relevant allergens in the production facility, staff sensitization and training, and taking into account all areas of production from incoming raw materials to outgoing goods.For the evaluation of unavoidable cross-contacts, it is possible today to draw on data from clinical trials for many of the substances that are subject to labelling. This data can be used to assess the risk of the final product.However, the data from threshold studies is not legally binding, so it is left to the manufacturer to assess the level up to which the food is safe for the allergic. In particular the non-harmonized approach of the EU member countries' food safety authorities currently represents a major obstacle, as this can lead to food recalls even though existing levels were evaluated as being safe according to the risk assessments performed. PMID:27299344

  1. [Cross reactivity of food allergens and its clinical relevance].

    PubMed

    Moneret-Vautrin, Denise Anne

    2005-10-01

    Cross-reactions between food allergens and other allergens are a major focus of interest. They include cross-allergies between Betulaceae and Compositae pollen, and also between fruits and vegetables (Prunoideae and Apiaceae). Cross-allergies between animal allergens include mites, cockroaches and crustaceans, milk and meat, animal epithelia, meat and egg. Cross-reactivity results from homology between protein sequences, and is highly likely when this homology reaches about 70%. Phylogenetically similar proteins occur in all species and are known as pan allergens. Profilins, Bet v1 homologues, and lipid transfer proteins have varying degrees of clinical relevance. The involvement of cross-reactivity in the persistence of sensitization and in allergic disorders is unclear. The consequences of cross-reactivity during specific immunotherapy with total allergenic extracts are random. Interpretation of biological tests of IgE binding is also biased by cross-reactivity. The use of panels of major recombinant allergens should help to identify specific sensitization profiles as well as clinically relevant sensitization. Cross-reactivity between epitopes of inhalants and of food allergens may perpetuate and intensify allergic disorders. The consequences of cross-reactivity between allergens and autologous proteins are unknown. PMID:16669147

  2. Topical Immunotherapy in Alopecia Areata

    PubMed Central

    Singh, Gurcharan; Lavanya, MS

    2010-01-01

    Alopecia Areata (AA) is a common non-scarring alopecia directed against the anagenic hair follicle. Various treatment modalities have been used for the treatment of severe AA. Topical immunotherapy is the best documented treatment so far for severe and refractory AA. Dinitrochlorobenzene (DNCB), squaric acid dibutylester (SADBE), and diphencyprone (DPCP) are the contact allergens used for this purpose. DNCB has been found to be mutagenic by the Ames test and is largely replaced by DPCP and SADBE. DPCP and SADBE are both known to be non-mutagenic compounds and have comparable efficacy results and relapse rates. SADBE requires special solvents and additives to maintain its potency and is more expensive than the rest. DPCP has a response rate varying from 60% in severe Alopecia Areata to 17% in patients with alopecia totalis or universalis, and shows about 88 to 100% high response rate in patients with patchy Alopecia Areata. PMID:21188022

  3. Medical-legal considerations in the practice of allergy: personal reflections on lessons learned from an immunotherapy fatality.

    PubMed

    Hallett, Jeffrey S

    2004-01-01

    Fatalities after administration of specific allergen immunotherapy are rare occurrences in a general allergy practice, as is medical negligence litigation. The author has experienced both and now relates his personal reflections on the lessons that were learned from the experiences. The twelve lessons that are reviewed encompass observations that are relevant not only to immunotherapy litigation but also to any general medical negligence litigation that one might encounter. Three principles of practice that are specific for allergen immunotherapy administration and that were closely scrutinized during the litigation are also reviewed. PMID:15709451

  4. Identification and characterization of major cat allergen Fel d 1 mimotopes on filamentous phage carriers.

    PubMed

    Luzar, Jernej; Molek, Peter; Šilar, Mira; Korošec, Peter; Košnik, Mitja; Štrukelj, Borut; Lunder, Mojca

    2016-03-01

    Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy. PMID:26908079

  5. Sublingual immunotherapy: a comprehensive review.

    PubMed

    Cox, Linda S; Larenas Linnemann, Désirée; Nolte, Hendrik; Weldon, David; Finegold, Ira; Nelson, Harold S

    2006-05-01

    Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non-cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients. PMID:16675328

  6. Immunological aspects of the immune response induced by mosquito allergens.

    PubMed

    Cantillo, José Fernando; Fernández-Caldas, Enrique; Puerta, Leonardo

    2014-01-01

    Allergies caused by mosquito bites may produce local or systemic reactions. The inhalation of mosquito allergens may also cause asthma and/or allergic rhinoconjunctivitis in sensitized individuals. The mechanisms implicated in the development of these immune responses involve IgE antibodies, different subtypes of IgG and proinflammatory cytokines as well as basophils, eosinophils and mast cells. Several allergenic components have been identified in the saliva and bodies of mosquitoes and some of these are present in different mosquito species. The most common species implicated in allergic reactions belong to the genera Aedes, Culex and Anopheles. Several Aedes aegypti allergens have been cloned and sequenced. The recombinant molecules show IgE reactivity similar to that of the native allergens, making them good candidates for the diagnosis of mosquito allergies. Allergen-specific immunotherapy with mosquito extracts induces a protective response characterized by a decreased production of IgE antibodies, increased IgG levels, a reduction in the severity of cutaneous and respiratory symptoms and the need for medication. The aims of this review are to summarize the progress made in the characterization of mosquito allergens and discuss the types of immune responses induced by mosquito bites and the inhalation of mosquito allergens in atopic individuals. PMID:25661054

  7. Transition of recombinant allergens from bench to clinical application.

    PubMed

    Cromwell, Oliver; Suck, Roland; Kahlert, Helga; Nandy, Andreas; Weber, Bernhard; Fiebig, Helmut

    2004-03-01

    The cloning and production of an increasing number of allergens through the use of DNA technology has provided the opportunity to use these proteins instead of natural allergen extracts for the diagnosis and therapy of IgE-mediated allergic disease. For diagnostic purposes, it is essential that the molecules exhibit IgE-reactivity comparable with that of the natural wild-type molecules, whereas T cell reactivity and immunogenic activity may be more important for allergen-specific immunotherapy. In relation to the latter, the development of hypoallergenic recombinant allergen variants is an approach which shows great promise. Clinical application of the proteins requires that they must be produced under conditions of Good Manufacturing Practice and meet the specifications set down in the appropriate Regulatory Guidelines, principally the ICH-Guidelines. Special consideration has to be given to the choice of expression system, the design of the expression vectors, and the purification strategy to obtain a pure product free from toxins and contamination. The availability of the pure recombinant molecules provides the opportunity to formulate preparations that are free from the non-allergenic ballast proteins present in natural allergen extracts and which contain relative concentrations of the allergens in clinically appropriate proportions. PMID:14962765

  8. Peanut allergens: an overview.

    PubMed

    Sáiz, Jorge; Montealegre, Cristina; Marina, Maria Luisa; García-Ruiz, Carmen

    2013-01-01

    Peanut is recognized as a potent food allergen producing one of the most frequent food allergies. This fact has originated the publication of an elevated number of scientific reports dealing with peanut allergens and, especially, the prevalence of peanut allergy. For this reason, the information available on peanut allergens is increasing and the debate about peanut allergy is always renewed. This article reviews the information currently available on peanut allergens and on the techniques used for their chemical characterization. Moreover, a general overview on the current biotechnological approaches used to reduce or eliminate peanut allergens is also provided. PMID:23638932

  9. [From the allergen-recognition by antibodies to new therapeutic concepts].

    PubMed

    Hantusch, Brigitte; Jensen-Jarolim, Erika

    2008-01-01

    Cross-linking of IgE antibodies through allergens is a basic event in type I allergy and leads to the immediate release of mediators like histamine, responsible for allergic symptoms like rhino-conjunctivitis or asthma. Critical for the binding of allergens to IgE are the IgE-epitopes, which represent a congregation of several amino acid residues often derived from different regions of the allergen. By means of the mimotope-technology, we isolated peptides from phage libraries, which were able to structurally mimic IgE-epitopes of the plant allergens Bet v 1 (birch) and Phl p 5a (timothy grass). Hence, these are candidates for an epitope-specific immunotherapy. In this mode of immunotherapy, it is the aim to induce IgG antibodies directed exclusively against the IgE-epitopes of allergens without induction of anaphylactogenic IgG species, and without the risk of anaphylaxis through cross-linking of IgE. Immunizing mice, we applied the mimotopes displayed on bacteriophages as well as on alternative carrier systems to enhance their antigenicity. With these systems it was possible to elicit an allergen-specific immune response, which was also accompanied by the appropriate T-cell help. Mimotopes resemble a promising concept for an epitope-tailored immunotherapy of allergic patients. PMID:18286245

  10. Lean and Agile Development of the AITS Ground Software System

    NASA Astrophysics Data System (ADS)

    Richters, Mark; Dutruel, Etienne; Mecredy, Nicolas

    2013-08-01

    We present the ongoing development of a new ground software system used for integrating, testing and operating spacecraft. The Advanced Integration and Test Services (AITS) project aims at providing a solution for electrical ground support equipment and mission control systems in future Astrium Space Transportation missions. Traditionally ESA ground or flight software development projects are conducted according to a waterfall-like process as specified in the ECSS-E-40 standard promoted by ESA in the European industry. In AITS a decision was taken to adopt an agile development process. This work could serve as a reference for future ESA software projects willing to apply agile concepts.

  11. Allergenicity of Peanut Proteins is Retained Following Enzymatic Hydrolysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rationale: Hydrolysis of peanut proteins by food-grade enzymes may reduce allergenicity and could lead to safer forms of immunotherapy. Methods: Light roasted peanut flour extracts were digested with pepsin (37°C, pH 2), Alcalase (60°C pH 8), or Flavourzyme (50°C, pH 7) up to 1 hr, or sequentially w...

  12. An update on immunotherapy for food allergy

    PubMed Central

    Scurlock, Amy M.; Jones, Stacie M.

    2013-01-01

    Purpose of the review Recent investigation has resulted in significant advances toward definitive therapeutic options for food allergy. In this review, we will explore novel immunotherapeutic interventions for the active treatment of food allergy. Recent findings Because the injection route for allergen immunotherapy to foods has been associated with an unacceptable risk of severe anaphylactic reactions, use of mucosally targeted therapeutic strategies is of significant interest for food allergy. Allergen-specific immunotherapeutic approaches such as oral, sublingual, epicutaneous, and peptide immunotherapy have demonstrated efficacy in increasing threshold dose and inducing immunologic changes associated with both desensitization and oral tolerance in animal and human trials. More global immunomodulatory strategies, such as Traditional Chinese Medicine and anti-IgE therapy have been shown to effectively target the allergic response, and clinical trials are ongoing to determine the efficacy and safety in human food allergy. Summary The advent of therapies that target the mucosal immune response to promote oral tolerance have shown great promise in the treatment of food hypersensitivity. However, there is still significant risk of adverse reactions associated with these therapeutic strategies and further study is needed to carefully advance these therapeutic modalities toward general clinical implementation. PMID:20856110

  13. Immunotherapy for lung cancer.

    PubMed

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W

    2016-07-01

    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy. PMID:27101251

  14. Venom immunotherapy modulates interleukin-4 and interferon-gamma messenger RNA expression of peripheral T lymphocytes.

    PubMed Central

    Akoum, H; Tsicopoulos, A; Vorng, H; Wallaert, B; Dessaint, J P; Joseph, M; Hamid, Q; Tonnel, A B

    1996-01-01

    The mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. In order to evaluate the influence of venom immunotherapy on the T-cell cytokine pattern of allergic reactions, we studied interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) mRNA expression of peripheral T lymphocytes from 12 patients undergoing rush venom desensitization, before treatment at Day 0 (D0), at Day 15 (D15) and Day 90 (D90) after treatment, and from seven controls. Antigen-specific T-cell proliferation was also determined. Cytokine mRNA expression was evaluated using in situ hybridization, 24 hr after culture of peripheral T cells with medium, venom, or an unrelated allergen. Allergen-induced T-cell proliferation decreased at D15 and D90 of rush immunotherapy (P < or = 0.02). In venom-stimulated cultures of the patient group, there was a decrease in IL-4 mRNA-positive cells at D15 and D90 (P < or = 0.001). Before desensitization, IFN-gamma mRNA expression was lower in patients than in controls and did not increase after in vitro allergen stimulation. In contrast, after immunotherapy, spontaneous IFN-gamma mRNA expression increased, but only at D90 (P < or = 0.001). The cytokine pattern observed at D90 after immunotherapy was similar to that observed in control subjects. In conclusion, venom immunotherapy induced an altered cytokine mRNA pattern in allergen-stimulated T cells which was dissociated from the early changes of allergen-induced T-cell responsiveness. PMID:8675214

  15. AIT's ThinkAbout: ITV Bridge to the 1980s.

    ERIC Educational Resources Information Center

    Carlisle, Robert D. B.

    1979-01-01

    Chronicles the development and promise for the future of ThinkAbout, the first step in AIT's effort to embody "Skills Essential to Learning" in televised instruction. The series will debut in fifth- and sixth-grade classrooms in September and is funded by 35 states and Canadian provinces, CPB, and Exxon. (Author/CMV)

  16. Mechanisms of immunotherapy to wasp and bee venom.

    PubMed

    Ozdemir, C; Kucuksezer, U C; Akdis, M; Akdis, C A

    2011-09-01

    Hymenoptera venoms are important allergens that can elicit both local and systemic allergic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the most effective treatment, reducing the risk of systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore normal immunity against venom allergens and provide patients with a lifetime of tolerance to venoms. During VIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T (Treg) cells, which suppress proliferative and cytokine responses against the venom allergens. Treg cells are characterized by IL-10 secretion that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Treg cells also have influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies against venom allergens. An accumulating body of evidence suggests that Treg cells may affect allergen sensitization and methods for enhancing this cell population may eventually improve the efficacy of VIT. In this article, immune mechanisms enrolled in bee and wasp VIT are reviewed. PMID:21729181

  17. Constructing a hybrid molecule with low capacity of IgE binding from Chenopodium album pollen allergens.

    PubMed

    Nouri, Hamid Reza; Varasteh, Abdolreza; Vahedi, Fatemeh; Chamani, Jamshidkhan; Afsharzadeh, Danial; Sankian, Mojtaba

    2012-05-30

    Allergen specific immunotherapy is the only remedy to prevent the progression of allergic diseases. Nowadays, using of recombinant allergens with reduced IgE-binding capacity is an ideal tool for allergen immunotherapy. Therefore, in this study we focused on a hybrid molecule (HM) production with reduced IgE reactivity from Chenopodium album pollen allergens. By means of genetic engineering, a head to tail structure of the three allergens of the C. album pollen was designed. The resulting DNA construct coding for a 46kDa HM was inserted into an expression vector and expressed as hexahistidine tagged fusion protein in Escherichia coli. IgE reactivity of the HM was evaluated by western blotting, inhibition ELISA and in vivo skin prick test and its immunogenic property was tested by proliferation assay. The recombinant HM was expressed and purified by nickel-affinity chromatography. Comparison of the recombinant HM with a mixture of three recombinant allergens, as well as natural allergens in the whole C. album pollen extract via immunological experiments revealed that it has a much lower potential of IgE reactivity. Furthermore, in vivo skin prick tests showed that it has a significantly lower potency to induce cutaneous reactions than the mixture of recombinant wild type allergens and whole extract while, it had been preserved immunogenic properties. Our results have demonstrated that assembling three allergens of C. album in a hybrid molecule can reduce its IgE reactivity. PMID:22504204

  18. Food processing and allergenicity.

    PubMed

    Verhoeckx, Kitty C M; Vissers, Yvonne M; Baumert, Joseph L; Faludi, Roland; Feys, Marcel; Flanagan, Simon; Herouet-Guicheney, Corinne; Holzhauser, Thomas; Shimojo, Ryo; van der Bolt, Nieke; Wichers, Harry; Kimber, Ian

    2015-06-01

    Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat treatment) on the allergenic potential of proteins, and on the antigenic (IgG-binding) and allergenic (IgE-binding) properties of proteins has been considered. A variety of allergenic foods (peanuts, tree nuts, cows' milk, hens' eggs, soy, wheat and mustard) have been reviewed. The overall conclusion drawn is that processing does not completely abolish the allergenic potential of allergens. Currently, only fermentation and hydrolysis may have potential to reduce allergenicity to such an extent that symptoms will not be elicited, while other methods might be promising but need more data. Literature on the effect of processing on allergenic potential and the ability to induce sensitisation is scarce. This is an important issue since processing may impact on the ability of proteins to cause the acquisition of allergic sensitisation, and the subject should be a focus of future research. Also, there remains a need to develop robust and integrated methods for the risk assessment of food allergenicity. PMID:25778347

  19. Antigen-based immunotherapy for autoimmune disease: current status

    PubMed Central

    Hirsch, Darren Lowell; Ponda, Punita

    2015-01-01

    Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease. PMID:27471707

  20. Proteomic analysis and candidate allergenic proteins in Populus deltoides CL. "2KEN8" mature pollen.

    PubMed

    Zhang, Jin; Wu, Li-Shuan; Fan, Wei; Zhang, Xiao-Ling; Jia, Hui-Xia; Li, Yu; Yin, Ya-Fang; Hu, Jian-Jun; Lu, Meng-Zhu

    2015-01-01

    Proteomic analysis was used to generate a map of Populus deltoides CL. "2KEN8" mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy. PMID:26284084

  1. Immunotherapy with the storage mite lepidoglyphus destructor.

    PubMed

    Armentia-Medina, A; Tapias, J A; Martín, J F; Ventas, P; Fernández, A

    1995-01-01

    We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12 months of specific hyposensitization (Abelló Lab., Spain) we performed in vivo (skin tests with Ld, methacholine and challenge tests), and in vitro tests (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to their major allergen Lep dI). We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls (symptoms and medication score, detection of immune complexes). After therapy we found a significant decrease in specific skin reactivity, dose of positive challenge tests, and hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI. The placebo group showed no changes in these variables. There were no severe secondary reactions after treatment with the extract. Patients-self-evaluation was favourable and their labour absence decreased. No development of circulating immune complexes was associated with this immunotherapy. PMID:8526179

  2. Sublingual or subcutaneous immunotherapy for allergic rhinitis?

    PubMed

    Durham, Stephen R; Penagos, Martin

    2016-02-01

    Allergen immunotherapy is effective in patients with allergic rhinitis (AR) and, unlike antiallergic drugs, has been shown to modify the underlying cause of the disease, with proved long-term benefits. Subcutaneous immunotherapy (SCIT) has been the gold standard, whereas sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative. Previous Cochrane systematic reviews and meta-analyses have confirmed that both SLIT and SCIT are effective in patients with seasonal AR, whereas evidence for their efficacy in patients with perennial disease has been less convincing. Recent large, adequately powered trials have demonstrated reductions in both symptoms and use of rescue medication in patients with seasonal and those with perennial AR. Here we appraise evidence for SCIT versus SLIT based on indirect evidence from Cochrane reviews and recent well-powered double-blind, randomized controlled trials versus placebo and the limited direct evidence available from randomized blind head-to-head comparisons. At present, based on an overall balance of efficacy and side effects, the patient is in equipoise. Pending definitive comparative trials, choice might be determined largely by the local availability of SCIT and SLIT products of proved value and personal (patient) preference. PMID:26853126

  3. Efficacy of Sublingual Immunotherapy with Dermatophagoides farinae Extract in Monosensitized and Polysensitized Patients with Allergic Rhinitis: Clinical Observation and Analysis

    PubMed Central

    Xu, Chen-Xia; Zhang, Miao-Lian; Li, Bi-Zhou; He, Ying; Zou, Ze-Hong; Wu, Qiu-Rong; Tao, Ai-Lin; Lai, He; Sun, Jin-Lu

    2015-01-01

    Aim. To investigate differences in the efficacy of sublingual immunotherapy with Dermatophagoides farinae drops in monosensitized and polysensitized allergic rhinitis patients. Methods. The patients enrolled in the study were treated for more than one year by sublingual immunotherapy (SLIT) using Dermatophagoides farinae drops and were divided into a monosensitized group (n = 20) and a polysensitized group (n = 30). Total nasal symptom scores of patients before and after SLIT were analyzed to evaluate the curative effect. The phylogenetic tree of dust mite allergens as well as other allergens that were tested by skin prick test was constructed to help the analysis. Results. There was no significant difference in the efficacy of SLIT between dust mite monosensitized and polysensitized patients. Conclusions. Both dust mite monosensitized and polysensitized patients could be cured by SLIT using Dermatophagoides farinae drops. This study provides a reference for the selection of allergens to be used in immunotherapy for polysensitized AR patients. PMID:26000283

  4. Removing Peanut Allergen Ara h 1 from Peanut Extracts Using p-Aminobenzamidine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rationale: Ara h 1 is one of 3 major allergens in peanut. Removing Ara h 1 from a peanut extract may produce a hypoallergenic peanut extract for immunotherapy and other purposes. Methods: Peanut extracts were treated overnight with and without 10 mM p-aminobenzamidine (pABA, a protease inhibitor) i...

  5. Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review.

    PubMed

    Röder, Esther; Berger, Marjolein Y; de Groot, Hans; van Wijk, Roy Gerth

    2008-05-01

    Allergen-specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non-invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on the efficacy of immunotherapy in all its different administration forms in youngsters. Therefore, we systematically reviewed randomized controlled trials (RCTs) to evaluate the effect of immunotherapy with inhalant allergens on symptoms and medication use in children and adolescents with allergic rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register and reference lists of recent reviews and published trials were searched. RCTs including youngsters aged 0-18 yr with allergic rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic treatment or a different administration form of immunotherapy were included. Primary outcome measures were rhinoconjunctivitis symptom and/or medication scores. Methodological quality was assessed using the validated Delphi list. A method of best evidence synthesis, a rating system with levels of evidence based on the overall quality and the outcome of the trials, was used to assess efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11 sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were included. Only 39% of the trials were of high methodological quality. For the SCIT and OIT subgroups the level of evidence for efficacy was conflicting. Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup showed no evidence of effect. The evidence for the perennial and seasonal allergen trials within the subgroups varied from moderate evidence of effect to no evidence of effect. In conclusion, there is at present insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in

  6. Mining Novel Allergens from Coconut Pollen Employing Manual De Novo Sequencing and Homology-Driven Proteomics.

    PubMed

    Saha, Bodhisattwa; Sircar, Gaurab; Pandey, Naren; Gupta Bhattacharya, Swati

    2015-11-01

    Coconut pollen, one of the major palm pollen grains is an important constituent among vectors of inhalant allergens in India and a major sensitizer for respiratory allergy in susceptible patients. To gain insight into its allergenic components, pollen proteins were analyzed by two-dimensional electrophoresis, immunoblotted with coconut pollen sensitive patient sera, followed by mass spectrometry of IgE reactive proteins. Coconut being largely unsequenced, a proteomic workflow has been devised that combines the conventional database-dependent analysis of tandem mass spectral data and manual de novo sequencing followed by a homology-based search for identifying the allergenic proteins. N-terminal acetylation helped to distinguish "b" ions from others, facilitating reliable sequencing. This led to the identification of 12 allergenic proteins. Cluster analysis with individual patient sera recognized vicilin-like protein as a major allergen, which was purified to assess its in vitro allergenicity and then partially sequenced. Other IgE-sensitive spots showed significant homology with well-known allergenic proteins such as 11S globulin, enolase, and isoflavone reductase along with a few which are reported as novel allergens. The allergens identified can be used as potential candidates to develop hypoallergenic vaccines, to design specific immunotherapy trials, and to enrich the repertoire of existing IgE reactive proteins. PMID:26426307

  7. Lipocalins as allergens.

    PubMed

    Mäntyjärvi, R; Rautiainen, J; Virtanen, T

    2000-10-18

    The term allergy refers to clinical conditions caused by an inappropriate immune response to innocuous proteins in genetically predisposed persons. Allergens of animal origin are responsible for a significant proportion of allergies. In recent years, it has become evident that practically all respiratory animal allergens characterized at the molecular level belong to the lipocalin family of proteins. The current list comprises the major allergens of horse, cow, dog, mouse, rat and cockroach as well as beta-lactoglobulin of cow's milk. While the molecular structure of all these allergens is known, far less information is available regarding their immunological characteristics. Knowing the way the immune system recognizes these allergens and reacts to them might, however, be the key for discovering the common denominator of the allergenicity of lipocalins. The human body contains numerous endogenous lipocalins, and the immune system has to adapt to their presence. We have proposed that under these conditions the immune response against the lipocalin allergens which are structurally related to endogenous lipocalins might be the pathway to allergy in genetically predisposed persons. The same might well apply also to other allergens with homologous endogenous counterparts. PMID:11058771

  8. PEANUT ALLERGENS AND PROCESSING

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that boiling or frying peanuts leads to less allergenic products than roasting. In this study, we have compared the fate of the major peanut allergens in the context of peanuts subjected to boiling, frying, or roasting. As opposed to previous work, both the soluble and insolubl...

  9. Peanut Allergens and Processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that boiling or frying of peanuts lead to less allergenic products than roasting. In this study, we have compared the fate of the major peanut allergens in the context of peanuts subjected to boiling, frying, or roasting. As opposed to previous work, both the soluble and insolu...

  10. Tree nut allergens.

    PubMed

    Roux, Kenneth H; Teuber, Suzanne S; Sathe, Shridhar K

    2003-08-01

    Allergic reactions to tree nuts can be serious and life threatening. Considerable research has been conducted in recent years in an attempt to characterize those allergens that are most responsible for allergy sensitization and triggering. Both native and recombinant nut allergens have been identified and characterized and, for some, the IgE-reactive epitopes described. Some allergens, such as lipid transfer proteins, profilins, and members of the Bet v 1-related family, represent minor constituents in tree nuts. These allergens are frequently cross-reactive with other food and pollen homologues, and are considered panallergens. Others, such as legumins, vicilins, and 2S albumins, represent major seed storage protein constituents of the nuts. The allergenic tree nuts discussed in this review include those most commonly responsible for allergic reactions such as hazelnut, walnut, cashew, and almond as well as those less frequently associated with allergies including pecan, chestnut, Brazil nut, pine nut, macadamia nut, pistachio, coconut, Nangai nut, and acorn. PMID:12915766

  11. Dimerization of lipocalin allergens

    PubMed Central

    Niemi, Merja H.; Rytkönen-Nissinen, Marja; Miettinen, Ilja; Jänis, Janne; Virtanen, Tuomas; Rouvinen, Juha

    2015-01-01

    Lipocalins are one of the most important groups of inhalant animal allergens. The analysis of structural features of these proteins is important to get insights into their allergenicity. We have determined two different dimeric crystal structures for bovine dander lipocalin Bos d 2, which was earlier described as a monomeric allergen. The crystal structure analysis of all other determined lipocalin allergens also revealed oligomeric structures which broadly utilize inherent structural features of the β-sheet in dimer formation. According to the moderate size of monomer-monomer interfaces, most of these dimers would be transient in solution. Native mass spectrometry was employed to characterize quantitatively transient dimerization of two lipocalin allergens, Bos d 2 and Bos d 5, in solution. PMID:26346541

  12. Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice.

    PubMed

    Gregory, James A; Shepley-McTaggart, Ariel; Umpierrez, Michelle; Hurlburt, Barry K; Maleki, Soheila J; Sampson, Hugh A; Mayfield, Stephen P; Berin, M Cecilia

    2016-07-01

    Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen-specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut-allergic patients. We further found that immunotherapy using algal-produced Ara h 1 core domain confers protection from peanut-induced anaphylaxis in a murine model of peanut allergy. PMID:26801740

  13. Clinical and Immunological Changes of Immunotherapy in Patients with Atopic Dermatitis: Randomized Controlled Trial

    PubMed Central

    Sánchez Caraballo, Jorge Mario; Cardona Villa, Ricardo

    2012-01-01

    Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients. PMID:23724240

  14. Specific Immunotherapy in Atopic Dermatitis

    PubMed Central

    Lee, Jungsoo; Park, Chang Ook

    2015-01-01

    Allergen specific immunotherapy (SIT) using house dust mite (HDM) extracts has been performed mainly with patients of asthma and allergic rhinitis. In the meanwhile, there has been a long debate on the efficacy of SIT in atopic dermatitis (AD) with only a few double-blind placebo-controlled trials. However, several randomized controlled trials of SIT in AD revealed significant improvement of clinical symptoms and also, positive result was shown by a following meta-analysis study of these trials. In order to predict and evaluate the treatment outcome, finding a biomarker that can predict treatment responses and treatment end-points is critical but it is very challenging at the same time due to the complexity of causes and mechanisms of AD. Other considerations including standardization of the easiest and safest treatment protocol and optimizing the treatment preparations should be studied as well. This review summarizes the basics of SIT in AD including the brief mechanisms, treatment methods and schedules, and also highlights the clinical efficacy of SIT in AD along with mild, controllable adverse reactions. Immunologic effects and studies of various biomarkers are also introduced and finally, future considerations with upcoming studies on SIT were discussed. PMID:25749758

  15. Inhaled allergen bronchoprovocation tests.

    PubMed

    Diamant, Zuzana; Gauvreau, Gail M; Cockcroft, Don W; Boulet, Louis-Philippe; Sterk, Peter J; de Jongh, Frans H C; Dahlén, Barbro; O'Byrne, Paul M

    2013-11-01

    The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and experienced investigators, it is safe and highly reproducible. In combination with validated airway sampling and sensitive detection techniques, allergen challenge allows the study of several features of the physiology of mainly TH2 cell-driven asthma in relation to the kinetics of the underlying airway pathology occurring during the allergen-induced late response. Furthermore, given the small within-subject variability in allergen-induced airway responses, allergen challenge offers an adequate disease model for the evaluation of new (targeted) controller therapies for asthma in a limited number of subjects. In proof-of-efficacy studies thus far, allergen challenge showed a fair positive predicted value and an excellent negative predictive value for the actual clinical efficacy of new antiasthma therapies, underscoring its important role in early drug development. In this review we provide recommendations on challenge methods, response measurements, sample size, safety, and harmonization for future applications. PMID:24119772

  16. Allergen-induced asthma

    PubMed Central

    Cockcroft, Donald W

    2014-01-01

    It was only in the late 19th century that specific allergens, pollen, animal antigens and, later, house dust mite, were identified to cause upper and lower airway disease. Early allergen challenge studies, crudely monitored before measurement of forced expiratory volume in 1 s became widespread in the 1950s, focused on the immediate effects but noted in passing prolonged and/or recurrent asthma symptoms. The late asthmatic response, recurrent bronchoconstriction after spontaneous resolution of the early responses occurring 3 h to 8 h or more postchallenge, has been identified and well characterized over the past 50 years. The associated allergen-induced airway hyper-responsiveness (1977) and allergen-induced airway inflammation (1985) indicate that these late sequelae are important in the mechanism of allergen-induced asthma. Allergens are now recognized to be the most important cause of asthma. A standardized allergen inhalation challenge model has been developed and is proving to be a valuable research tool in the investigation of asthma pathophysiology and of potential new pharmacological agents for the treatment of asthma. PMID:24791256

  17. T-cell regulatory mechanisms in specific immunotherapy.

    PubMed

    Jutel, Marek; Akdis, Cezmi A

    2008-01-01

    Allergen-specific immunotherapy (SIT) is the only treatment which leads to a lifelong tolerance against previously disease-causing allergens due to restoration of normal immunity against allergens. The description of T-regulatory (Treg) cells being involved in prevention of sensitization to allergens has led to great interest whether they represent a major target for allergen-SIT and whether it would be possible to manipulate Treg cells to increase its efficacy. Activationinduced cell death, anergy and/or immune response modulation by Treg cells are essential mechanisms of peripheral T-cell tolerance. There is growing evidence that anergy, tolerance and active suppression are not entirely distinct, but rather represent linked mechanisms possibly involving the same cells and multiple suppressor mechanisms. Skewing of allergen-specific effector T cells to Treg cells appears as a crucial event in the control of healthy immune response to allergens and successful allergen-SIT. The Treg cell response is characterized by abolished allergen- induced specific T-cell proliferation and suppressed Thelper (Th)1- and Th2-type cytokine secretion. In addition, mediators of allergic inflammation that trigger cAMP-associated G-protein-coupled receptors, such as histamine receptor-2, may contribute to peripheral tolerance mechanisms. The increased levels of interleukin-10 and transforming growth factor-Beta that are produced by Treg cells potently suppress IgE production, while simultaneously increasing production of non-inflammatory isotypes IgG4 and IgA, respectively. In addition, Treg cells directly or indirectly suppress effector cells of allergic inflammation such as mast cells, basophils and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms. It is associated with regulation of antibody isotypes and effector cells to the direction of a healthy immune response. By the application of the recent knowledge in Treg

  18. Modification of house dust mite allergens by monomethoxypolyethylene glycol. Allergenicity measured by in vitro and in vivo methods.

    PubMed

    Mosbech, H; Dreborg, S; Påhlman, I; Stahl Skov, P; Steringer, I; Weeke, B

    1988-01-01

    In animal models, allergen modification by coupling to monomethoxypolyethylene glycol (mPEG) molecules can reduce allergenicity of the extract and makes the allergen capable of suppressing boosted IgE response. To investigate in a human system the degree of attenuation implied by a mPEG modification of a house dust mite (Dermatophagoides pteronyssinus) extract, 55 adults with asthma caused by house dust mites were tested by skin prick test (SPT) and histamine release assay (HR). RAST inhibition was performed on sera from 6 additional patients. Modified extract containing 0.42 mmol mPEG/g protein was used for the analyses. In order to get the same response of the two extracts when assessed by HR and SPT, a median increase in concentration of 10-fold of the mPEG-modified extract compared to the unmodified extract was needed. Interindividual variation was limited. Sixty-four to 72% needed a dose increase within +/- half a decade from this value. In 42-49% of the patients, results from SPT and HR deviated less than half a decade. The relative potency of the modified extract as measured by RAST inhibition was reduced to 17-78% (mean 39%). Reduced allergenicity would by itself mean less side effects in immunotherapy. When planning such therapy it is important to know that mPEG modification reduces the allergenicity to a similar extent in a majority of patients. PMID:2448247

  19. Allergen composition analysis and allergenicity assessment of Chinese peanut cultivars.

    PubMed

    Wu, Zhihua; Zhou, Ningling; Xiong, Faqian; Li, Xin; Yang, Anshu; Tong, Ping; Tang, Ronghua; Chen, Hongbing

    2016-04-01

    Peanut (Arachis hypogaea) is among the eight major food allergens in the world. Several attempts have been made to decrease or eliminate the allergenicity of peanut. Systemic screening of thousands of peanut cultivars may identify peanut with low allergenicity. In this study, the allergen compositions of 53 Chinese peanut cultivars were characterized, and their allergenicity to sera IgE of Chinese patients and in a mouse model was assessed. Contents of total protein and allergens were quantified by SDS-PAGE and densitometry analysis on gel. Although the contents of allergens broadly varied among cultivars, they were related to one another. The IgE binding capacity of cultivars was tested by ELISA, and their allergenicity was further evaluated in a mouse model by oral sensitization. Results showed that the allergenicity of peanut was affected by allergen composition rather than a single allergen. Peanut cultivars with low allergenicity may contain more Ara h 3/4 (24 kDa), Ara h 2 and less Ara h 3/4 (43, 38, and 36 kDa), Ara h 6. Screening based on allergen composition would facilitate the identification of low-allergenic peanut. PMID:26593515

  20. Cancer immunotherapy in children

    Cancer.gov

    More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient

  1. Immunotherapy for Cervical Cancer

    Cancer.gov

    In an early phase NCI clinical trial, two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer.

  2. Trends in Cancer Immunotherapy

    PubMed Central

    Murphy, Joseph F.

    2010-01-01

    Modulation of the immune system for therapeutic ends has a long history, stretching back to Edward Jenner’s use of cowpox to induce immunity to smallpox in 1796. Since then, immunotherapy, in the form of prophylactic and therapeutic vaccines, has enabled doctors to treat and prevent a variety of infectious diseases, including cholera, poliomyelitis, diphtheria, measles and mumps. Immunotherapy is now increasingly being applied to oncology. Cancer immunotherapy attempts to harness the power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is capable of recognizing and eliminating tumor cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for cancer immunotherapy is to apply advances in cellular and molecular immunology and develop strategies that effectively and safely augment antitumor responses. PMID:20703326

  3. Laser-facilitated epicutaneous immunotherapy to IgE-mediated allergy.

    PubMed

    Kumar, Mudnakudu Nagaraju Kiran; Zhou, Chang; Wu, Mei X

    2016-08-10

    Allergen specific immunotherapy has been shown to be the only effective treatment for long-lasting clinical benefit to IgE-mediated allergic diseases, but a fewer than 5% of patients choose the treatment because of inconvenience and a high risk of anaphylaxis. Recently, epicutaneous allergen-specific immunotherapy (EPIT) has proven effective, yet with limitations owing to strong skin reactions. We demonstrate here safer and faster EPIT, named μEPIT, by delivering powdered allergen and adjuvants into many micropores in the epidermis. We fabricated a microarray patch fractionally coated with a powder mixture of ovalbumin (OVA) model allergen, CpG, and 1,25-dihydroxyvitamin D3 (VD3). Topical application of the patch onto laser-microperforated skin resulted in a high level of epidermal delivery while greatly minimizing allergen leakage into circulation system as compared to current subcutaneous immunotherapy (SCIT). Moreover, only three times of μEPIT over two weeks could sufficiently inhibit allergen-specific IgE responses in mice suffering OVA-induced airway hyperresponsivness (AHR), which was unattainable by eight times of SCIT over three weeks. Mechanistically, μEPIT preferably enhanced IgG2a production suggesting TH1-biased immune responses and induced a high level of T-regulatory (Treg) cells against repeated allergen sensitization. The immune tolerance was confirmed by marked reduction in airway wall thickness as well as eosinophil and neutrophil infiltration into the respiratory airway. The μEPIT represents a novel and painless technology to treat IgE-mediated allergic diseases with little local skin reaction and a minimal risk of anaphylaxis. PMID:27235977

  4. Allergens in the Lab.

    ERIC Educational Resources Information Center

    Fisher, Thomas M.

    1987-01-01

    Points out the health and legal implications related to laboratory substances that could cause allergic reactions. Presents a list of potential cosmetic allergens and irritants. Includes precautionary measures dealing with allergy situations. (ML)

  5. Allergens and thunderstorm asthma.

    PubMed

    Nasser, Shuaib M; Pulimood, Thomas B

    2009-09-01

    Thunderstorm-related asthma is increasingly recognized in many parts of the world. This review focuses on important advances in the understanding of the mechanism of the role of allergens, in particular fungal spores such as Alternaria, in asthma epidemics associated with thunderstorms. From our observations, we have proposed that the prerequisites for this phenomenon are as follows: 1) a sensitized, atopic, asthmatic individual; 2) prior airway hyperresponsiveness before a sudden, large allergen exposure; 3) a large-scale thunderstorm with cold outflow occurring at a time and location during an allergen season in which large numbers of asthmatics are outdoors; and 4) sudden release of large amounts of respirable allergenic fragments, particularly fungal spores such as Alternaria. PMID:19671382

  6. IMMUNOTHERAPY IN ACUTE LEUKEMIA

    PubMed Central

    Leung, Wing

    2010-01-01

    Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371

  7. Immunotherapy in lung cancer.

    PubMed Central

    Al-Moundhri, M.; O'Brien, M.; Souberbielle, B. E.

    1998-01-01

    More research and new treatment options are needed in all stages of lung cancer. To this end immunotherapy needs a revival in view of recent improved technologies and greater understanding of the underlying biology. In this review we discuss mechanisms of tumour immunotherapy, non-specific, specific and adoptive, with particular reference to a direct therapeutic action on all subtypes of lung cancer. PMID:9703271

  8. Immunotherapy to Treat Cancer.

    PubMed

    McCune, J S

    2016-09-01

    This issue of Clinical Pharmacology & Therapeutics focuses on immunotherapy as an approach to treat cancer by generating or augmenting an immune response against it. The enthusiasm for immunotherapy has waxed and waned over the past century. Enthusiasm for immunotherapy has risen over the past decade due, in part, to data showing that cancer immunotherapy consistently improves overall survival in select patients with advanced-stage cancer. Antitumor immunotherapy has broad potential and could be used to treat many different types of advanced-stage cancer due to the durable and robust response that it elicits across a diverse spectrum of cancers. This issue covers various aspects of relevant therapeutic topics ranging from discovery of chimeric antigen receptor (CAR) T cells, development of novel immunotherapies using novel pharmacokinetic/dynamic modeling tools, to the utilization of immune checkpoint therapy. Regarding utilization, this issue addresses biomarker selection strategies for personalized treatment of non-small cell lung cancer (NSCLC) with immune checkpoint therapy and also the management of the unique immune response adverse events (irAEs). PMID:27513619

  9. Multiplex component-based allergen microarray in recent clinical studies.

    PubMed

    Patelis, A; Borres, M P; Kober, A; Berthold, M

    2016-08-01

    During the last decades component-resolved diagnostics either as singleplex or multiplex measurements has been introduced into the field of clinical allergology, providing important information that cannot be obtained from extract-based tests. Here we review recent studies that demonstrate clinical applications of the multiplex microarray technique in the diagnosis and risk assessment of allergic patients, and its usefulness in studies of allergic diseases. The usefulness of ImmunoCAP ISAC has been validated in a wide spectrum of allergic diseases like asthma, allergic rhinoconjunctivitis, atopic dermatitis, eosinophilic esophagitis, food allergy and anaphylaxis. ISAC provides a broad picture of a patient's sensitization profile from a single test, and provides information on specific and cross-reactive sensitizations that facilitate diagnosis, risk assessment, and disease management. Furthermore, it can reveal unexpected sensitizations which may explain anaphylaxis previously categorized as idiopathic and also display for the moment clinically non-relevant sensitizations. ISAC can facilitate a better selection of relevant allergens for immunotherapy compared with extract testing. Microarray technique can visualize the allergic march and molecular spreading in the preclinical stages of allergic diseases, and may indicate that the likelihood of developing symptomatic allergy is associated with specific profiles of sensitization to allergen components. ISAC is shown to be a useful tool in routine allergy diagnostics due to its ability to improve risk assessment, to better select relevant allergens for immunotherapy as well as detecting unknown sensitization. Multiplex component testing is especially suitable for patients with complex symptomatology. PMID:27196983

  10. Quantitative Proteomic Profiling of Peanut Allergens in Food Ingredients Used for Oral Food Challenges.

    PubMed

    Johnson, Philip E; Sayers, Rebekah L; Gethings, Lee A; Balasundaram, Anuradha; Marsh, Justin T; Langridge, James I; Mills, E N Clare

    2016-06-01

    Profiling allergens in complex food ingredients used in oral food challenges and immunotherapy is crucial for regulatory acceptance. Mass spectrometry based analysis employing data-independent acquisition coupled with ion mobility mass spectrometry-mass spectrometry (DIA-IM-MS) was used to investigate the allergen composition of raw peanuts and roasted peanut flour ingredients used in challenge meals. This comprehensive qualitative and quantitative analysis using label-free approaches identified and quantified 123 unique protein accessions. Semiquantitative analysis indicated that allergens Ara h 1 and Ara h 3 were the most abundant proteins and present in approximately equal amounts and were extracted in reduced amounts from roasted peanut flours. The clinically significant allergens Ara h 2 and 6 were less abundant, but relative quantification was unaffected by roasting. Ara h 5 was undetectable in any peanut sample, while the Bet v 1 homologue Ara h 8 and the lipid transfer protein allergen, Ara h 9, were detected in low abundance. The oleosin allergens, Ara h 10 and 11, were moderately abundant in the raw peanuts but were 100-fold less abundant in the defatted roasted peanut flour than the major allergens Ara h 1, 3, 2, and 6. Certain isoforms of the major allergens dominated the profile. The relative quantitation of the major peanut allergens showed little variation between different batches of roasted peanut flour. These data will support future development of targeted approaches for absolute quantification of peanut allergens which can be applied to both food ingredients used in clinical studies and extracts used for skin testing and to identify trace levels of allergens in foods. PMID:27064171

  11. Sublingual immunotherapy (SLIT)--indications, mechanism, and efficacy: Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy.

    PubMed

    Jutel, Marek; Bartkowiak-Emeryk, Małgorzata; Bręborowicz, Anna; Cichocka-Jarosz, Ewa; Emeryk, Andrzej; Gawlik, Radosław; Gonerko, Paweł; Rogala, Barbara; Nowak-Węgrzyn, Anna; Samoliński, Bolesław

    2016-01-01

    SLIT (sublingual immunotherapy,) induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy), with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50-100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1-3 years has been provided by the large scale double-blind, placebo-controlled (DBPC) trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis) in both children and adults sensitized to pollen allergens (trees, grass, Parietaria), house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 - 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization. PMID:27012173

  12. Immunotherapy in gastric cancer

    PubMed Central

    Matsueda, Satoko; Graham, David Y

    2014-01-01

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright. PMID:24587645

  13. Mammalian lipocalin allergens--insights into their enigmatic allergenicity.

    PubMed

    Virtanen, T; Kinnunen, T; Rytkönen-Nissinen, M

    2012-04-01

    Most of the important mammal-derived respiratory allergens, as well as a milk allergen and a few insect allergens, belong to the lipocalin protein family. As mammalian lipocalin allergens are found in dander, saliva and urine, they disperse effectively and are widely present in the indoor environments. Initially, lipocalins were characterized as transport proteins for small, principally hydrophobic molecules, but now they are known to be involved in many other biological functions. Although the amino acid identity between lipocalins is generally at the level of 20-30%, it can be considerably higher. Lipocalin allergens do not exhibit any known physicochemical, functional or structural property that would account for their allergenicity, that is, the capacity to induce T-helper type 2 immunity against them. A distinctive feature of mammalian lipocalin allergens is their poor capacity to stimulate the cellular arm of the human or murine immune system. Nevertheless, they induce IgE production in a large proportion of atopic individuals exposed to the allergen source. The poor capacity of mammalian lipocalin allergens to stimulate the cellular immune system does not appear to result from the function of regulatory T cells. Instead, the T cell epitopes of mammalian lipocalin allergens are few and those examined have proved to be suboptimal. Moreover, the frequency of mammalian lipocalin allergen-specific CD4(+) T cells is very low in the peripheral blood. Importantly, recent research suggests that the lipocalin allergen-specific T cell repertoires differ considerably between allergic and healthy subjects. These observations are compatible with our hypothesis that the way CD4(+) T-helper cells recognize the epitopes of mammalian lipocalin allergens may be implicated in their allergenicity. Indeed, as several lipocalins exhibit homologies of 40-60% over species, mammalian lipocalin allergens may be immunologically at the borderline of self and non-self, which would not

  14. Proteomic analysis and candidate allergenic proteins in Populus deltoides CL. “2KEN8” mature pollen

    PubMed Central

    Zhang, Jin; Wu, Li-Shuan; Fan, Wei; Zhang, Xiao-Ling; Jia, Hui-Xia; Li, Yu; Yin, Ya-Fang; Hu, Jian-Jun; Lu, Meng-Zhu

    2015-01-01

    Proteomic analysis was used to generate a map of Populus deltoides CL. “2KEN8” mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy. PMID:26284084

  15. Oral immunotherapy and tolerance induction in childhood.

    PubMed

    Tang, M L K; Martino, D J

    2013-09-01

    Prevalence rates of food allergy have increased rapidly in recent decades. Of concern, rates of increase are greatest among children under 5 yrs of age and for those food allergies that persist into adulthood such as peanut or tree nut allergy and shellfish allergy. Given these trends, the overall prevalence of food allergy will compound over time as the number of children affected by food allergy soars and a greater proportion of food-allergic children are left with persistent disease into adulthood. It is therefore vital to identify novel curative treatment approaches for food allergy. Acquisition of oral tolerance to the diverse array of ingested food antigens and intestinal microbiota is an active immunologic process that is successfully established in the majority of individuals. In subjects who develop food allergy, there is a failure or loss of oral tolerance acquisition to a limited number of food allergens. Oral immunotherapy (OIT) offers a promising approach to induce specific oral tolerance to selected food allergens and represents a potential strategy for long-term curative treatment of food allergy. This review will summarize the current understanding of oral tolerance and clinical trials of OIT for the treatment of food allergy. PMID:23905867

  16. Positive reaction to allergen (image)

    MedlinePlus

    Allergic reaction is a sensitivity to a specific substance, called an allergen, that is contacted through the skin, inhaled into the lungs, swallowed or injected. The body's reaction to an allergen can be mild, such as ...

  17. [Current contact allergens].

    PubMed

    Geier, J; Uter, W; Lessmann, H; Schnuch, A

    2011-10-01

    Ever-changing exposure to contact allergens, partly due to statutory directives (e.g. nickel, chromate, methyldibromo glutaronitrile) or recommendations from industrial associations (e.g. hydroxyisohexyl 3-cyclohexene carboxaldehyde), requires on-going epidemiologic surveillance of contact allergy. In this paper, the current state with special focus in fragrances and preservatives is described on the basis of data of the Information Network of Departments of Dermatology (IVDK) of the year 2010. In 2010, 12,574 patients were patch tested in the dermatology departments belonging to the IVDK. Nickel is still the most frequent contact allergen. However the continuously improved EU nickel directive already has some beneficial effect; sensitization frequency in young women is dropping. In Germany, chromate-reduced cement has been in use now for several years, leading to a decline in chromate sensitization in brick-layers. Two fragrance mixes are part of the German baseline series; they are still relevant. The most important fragrances in these mixes still are oak moss absolute and hydroxyisohexyl 3-cyclohexene carboxaldehyde. However, in relation to these leading allergens, sensitization frequency to other fragrances contained in the mixes seems to be increasing. Among the preservatives, MCI/MI has not lost its importance as contact allergen, in contrast to MDBGN. Sources of MCI/MI sensitization obviously are increasingly found in occupational context. Methylisothiazolinone is a significant allergen in occupational settings, and less frequently in body care products. PMID:21901563

  18. Patient engagement and patient support programs in allergy immunotherapy: a call to action for improving long-term adherence.

    PubMed

    Demoly, Pascal; Passalacqua, Giovanni; Pfaar, Oliver; Sastre, Joaquin; Wahn, Ulrich

    2016-01-01

    Allergy immunotherapy (AIT) is acknowledged to produce beneficial mid- and long-term clinical and immunologic effects and increased quality of life in patients with allergic respiratory diseases (such as allergic rhinoconjunctivitis and allergic asthma). However, poor adherence to AIT (due to intentional and/or non-intentional factors) is still a barrier to achieving these benefits. There is an urgent need for patient support programs (PSPs) that encompass communication, educational and motivational components. In the field of AIT, a PSP should be capable of (1) improving adherence, (2) boosting patient engagement, (3) explaining how AIT differs from pharmacological allergy treatments; (4) increasing health literacy about chronic, progressive, immunoglobulin-E-mediated immune diseases, (5) helping the patient to understand and manage local or systemic adverse events, and (6) providing and/or predicting local data on aeroallergen levels. We reviewed the literature in this field and have identified a number of practical issues to be addressed when implementing a PSP for AIT: the measurement of adherence, the choice of technologies, reminders, communication channels and content, the use of "push" messaging and social networks, interactivity, and the involvement of caregivers and patient leaders. A key issue is "hi-tech" (i.e. approaches based mainly on information technology) vs. "hi-touch" (based mainly on interaction with humans, i.e. family members, patient mentors and healthcare professionals). We conclude that multistakeholder PSPs (combining patient-, provider and society-based actions) must now be developed and tested with a view to increasing adherence, efficacy and safety in the field of AIT. PMID:27478445

  19. [Allergenicity of lupin flour].

    PubMed

    Leduc, V; Moneret-Vautrin, D A; Guérin, L

    2002-06-01

    Lupin flour is used in human food for its high quality nutritional and functional qualities. The frequency of crossed allergy between lupin flour and peanuts, both members of the family of Leguminosae, is strong, since 68% of patients who are allergic to peanut have shown positive reactions to lupin flour when tested by TPO-DA. Cases of isolated allergy to lupin flour without pre-existence of peanut allergy as well as workplace asthma by inhalation are also rarely seen. The specific allergens of lupin and those that participate in crosses with peanut have been studied by SDS-PAGE and immunoblot. The diversity of allergens contained in different lupin flour has also been studied. Further, the detection of lupin flour in a "pizza" flour which induced a strong allergic reaction exposed its eventual implication as a masked allergen. PMID:12134645

  20. Redefining the major peanut allergens.

    PubMed

    Zhuang, Yonghua; Dreskin, Stephen C

    2013-03-01

    Food allergy has become a major public health concern in westernized countries, and allergic reactions to peanuts are particularly common and severe. Allergens are defined as antigens that elicit an IgE response, and most allergenic materials (e.g., pollens, danders, and foods) contain multiple allergenic proteins. This has led to the concept that there are "major" allergens and allergens of less importance. "Major allergens" have been defined as allergens that bind a large amount of IgE from the majority of patients and have biologic activity. However, the ability of an allergen to cross-link complexes of IgE and its high-affinity receptor FcεRI (IgE/FcεRI), which we have termed its allergic effector activity, does not correlate well with assays of IgE binding. To identify the proteins that are the most active allergens in peanuts, we and others have employed in vitro model assays of allergen-mediated cross-linking of IgE/FcεRI complexes and have demonstrated that the most potent allergens are not necessarily those that bind the most IgE. The importance of a specific allergen can be determined by measuring the allergic effector activity of that allergen following purification under non-denaturing conditions and by specifically removing the allergen from a complex allergenic extract either by chromatography or by specific immunodepletion. In our studies of peanut allergens, our laboratory has found that two related allergens, Ara h 2 and Ara h 6, together account for the majority of the effector activity in a crude peanut extract. Furthermore, murine studies demonstrated that Ara h 2 and Ara h 6 are not only the major elicitors of anaphylaxis in this system, but also can effectively desensitize peanut-allergic mice. As a result of these observations, we propose that the definition of a major allergen should be based on the potency of that allergen in assays of allergic effector activity and demonstration that removal of that allergen from an extract results in

  1. Evidence-based practice: sublingual immunotherapy for allergic rhinitis.

    PubMed

    Wise, Sarah K; Schlosser, Rodney J

    2012-10-01

    In this article, the authors review the current evidence regarding the public health and economic impact of allergic rhinitis. Diagnostic methods for allergic disease are discussed as well as certain nuances of allergy skin testing protocols. In addition, the evidence supporting sublingual immunotherapy (SLIT) for allergic rhinitis is reviewed, with subsequent attention to certain subgroups, such as adults and children, seasonal versus perennial allergens, and SLIT efficacy for individual antigens. The authors consider the evidence supporting appropriate SLIT dosing as well as the existing data on SLIT safety. PMID:22980684

  2. Grass pollen allergens globally: the contribution of subtropical grasses to burden of allergic respiratory diseases.

    PubMed

    Davies, J M

    2014-06-01

    Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies of grasses are major aeroallergen sources worldwide. The subtropical Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India, Asia, Australia and the Americas, where a large and increasing proportion of the world's population abide. These grasses are phylogenetically and ecologically distinct from temperate grasses. With the advent of global warming, it is conceivable that the geographic distribution of subtropical grasses and the contribution of their pollen to the burden of allergic rhinitis and asthma will increase. This review aims to provide a comprehensive synthesis of the current global knowledge of (i) regional variation in allergic sensitivity to subtropical grass pollens, (ii) molecular allergenic components of subtropical grass pollens and (iii) allergic responses to subtropical grass pollen allergens in relevant populations. Patients from subtropical regions of the world show higher allergic sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to temperate grass pollens. The group 1 allergens are amongst the allergen components of subtropical grass pollens, but the group 5 allergens, by which temperate grass pollen extracts are standardized for allergen content, appear to be absent from both subfamilies of subtropical grasses. Whilst there are shared allergenic components and antigenic determinants, there are additional clinically relevant subfamily-specific differences, at T- and B-cell levels, between pollen allergens of subtropical and temperate grasses. Differential immune recognition of subtropical grass pollens is likely to impact upon the efficacy of allergen immunotherapy of patients who are primarily sensitized to subtropical grass pollens. The literature reviewed herein highlights the clinical need to standardize allergen preparations for both

  3. Ole e 13 is the unique food allergen in olive: Structure-functional, substrates docking, and molecular allergenicity comparative analysis.

    PubMed

    Jimenez-Lopez, J C; Robles-Bolivar, P; Lopez-Valverde, F J; Lima-Cabello, E; Kotchoni, S O; Alché, J D

    2016-05-01

    Thaumatin-like proteins (TLPs) are enzymes with important functions in pathogens defense and in the response to biotic and abiotic stresses. Last identified olive allergen (Ole e 13) is a TLP, which may also importantly contribute to food allergy and cross-allergenicity to pollen allergen proteins. The goals of this study are the characterization of the structural-functionality of Ole e 13 with a focus in its catalytic mechanism, and its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering a) functional-regulatory motifs, b) comparative study of linear sequence, 2-D and 3D structural homology modeling, c) molecular docking with two different β-D-glucans, d) conservational and evolutionary analysis, e) catalytic mechanism modeling, and f) IgE-binding, B- and T-cell epitopes identification and comparison to other allergenic TLPs. Sequence comparison, structure-based features, and phylogenetic analysis identified Ole e 13 as a thaumatin-like protein. 3D structural characterization revealed a conserved overall folding among plants TLPs, with mayor differences in the acidic (catalytic) cleft. Molecular docking analysis using two β-(1,3)-glucans allowed to identify fundamental residues involved in the endo-1,3-β-glucanase activity, and defining E84 as one of the conserved residues of the TLPs responsible of the nucleophilic attack to initiate the enzymatic reaction and D107 as proton donor, thus proposing a catalytic mechanism for Ole e 13. Identification of IgE-binding, B- and T-cell epitopes may help designing strategies to improve diagnosis and immunotherapy to food allergy and cross-allergenic pollen TLPs. PMID:27017426

  4. House-dust mite allergy: mapping of Dermatophagoides pteronyssinus allergens for dogs by two-dimensional immunoblotting

    PubMed Central

    Marques, Andreia Grilo; Pereira, Luísa Maria Dotti Silva; Goicoa, Ana; Semião-Santos, Saul José; Bento, Ofélia Pereira

    2015-01-01

    Introduction Specific immunotherapy has shown to be very useful for allergy control in dogs, with a common success rate ranging from 65% to 70%. However, this efficacy could probably be improved and the identification of individual allergomes, with the choice of more adequate molecular allergen pools for specific immunotherapy, being the strategy. Aim To map Dermatophagoides pteronyssinus (Der p) allergens for mite-sensitized atopic dogs, for better understanding how individual allergograms may influence the response to house-dust mite immunotherapy. Material and methods To identify the Der p mite allergome for dogs, 20 individuals allergic to dust-mites and sensitized to Der p, were selected. The extract from Der p was submitted to isoelectric focusing (IEF), one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were blotted onto polyvinylidene difluoride (PVDF) membranes and immunoblottings were performed with patient sera. Allergen-bound specific IgE was detected. Results Eleven allergens were identified from isoelectric focusing (IEF), as well as from 1-D SDS PAGE. From 2-D SDS-PAGE, 24 spots were identified. Conclusions Several similarities were found between dog and human allergograms and no absolute correlation between sensitization and allergy was observed either. As in humans, different individual allergograms do not seem to implicate different clinical patterns, but may influence the response to specific immunotherapy. The molecular epidemiology approach in veterinary allergy management, by the characterization of individual patients’ allergoms and by choosing the best molecular allergen pool for each patient could also improve the efficacy of allergy immunotherapy. PMID:26015775

  5. Active Immunotherapy of Cancer.

    PubMed

    Chodon, Thinle; Koya, Richard C; Odunsi, Kunle

    2015-01-01

    Clinical progress in the field of cancer immunotherapy has been slow for many years but within the last 5 years, breakthrough successes have brought immunotherapy to the forefront in cancer therapy. Promising results have been observed in a variety of cancers including solid tumors and hematological malignancies with adoptive cell therapy using natural host tumor infiltrating lymphocytes, host cells that have been genetically engineered with antitumor T-cell receptors or chimeric antigen receptors, immune checkpoint inhibitors like anti-CTLA-4, anti-PD-1 or PD-L1 monoclonal antibodies and oncolytic virus-based immunotherapy. However, most treatment modalities have shown limited efficacy with single therapy. The complex nature of cancer with intra- and inter-tumor antigen and genomic heterogeneity coupled with the immune suppressive microenvironment emphasizes the prospect of personalized targeted immunotherapy to manipulate the patient's own immune system against cancer. For successful, robust and long-lasting cure of cancer, a multi-modal approach is essential, combining anti-tumor cell therapy with manipulation of multiple pathways in the tumor microenvironment to ameliorate tumor-induced immunosuppression. PMID:26575466

  6. Allergenicity of processed food.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Food allergies have become a major public health issue in many countries. In the U.S. it is estimated that approximately 150 individuals die each year from accidental ingestion of an allergic food. As a result, the federal government recently passed the food allergen labeling law which went into ef...

  7. Bleach Neutralizes Mold Allergens

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  8. Possible therapeutic potential of a recombinant group 2 grass pollen allergen-specific antibody fragment.

    PubMed

    Gadermaier, E; Flicker, S; Blatt, K; Valent, P; Valenta, R

    2014-02-01

    The induction of blocking IgG antibodies that compete with IgE for allergen binding is one important mechanism of allergen-specific immunotherapy. The application of blocking antibodies may be an alternative treatment strategy. A synthetic gene coding for a single-chain fragment (ScFv) specific for the major timothy grass pollen allergen Phl p 2 was inserted into plasmid pCANTAB 5 E, and the recombinant ScFv was expressed in Escherichia coli and purified by affinity chromatography. The ScFv was tested for allergen binding by ELISA, and its association and dissociation were measured by surface plasmon resonance (Biacore) technology. The ability of the ScFv to inhibit allergic patients' IgE binding to Phl p 2 and Phl p 2-induced basophil degranulation was studied by ELISA competition and basophil activation (CD203c) assays. We report the expression, purification, biochemical and immunological characterization of a monomeric single-chain fragment (ScFv) of human origin specific for the major timothy grass pollen allergen, Phl p 2. The Phl p 2-ScFv showed high affinity binding to the allergen and blocked the binding of allergic patients' polyclonal IgE to Phl p 2 up to 98%. Furthermore, it inhibited allergen-induced basophil activation. The Phl p 2-ScFv inhibited allergic patients' IgE binding to Phl p 2 as well as Phl p 2-induced basophil activation and might be useful for passive immunotherapy of grass pollen allergy. PMID:24251384

  9. 18 Proteomic and Immunological Characterization of Ragweed Allergens

    PubMed Central

    Augustin, Steffen; Stock, Marion; Cromwell, Oliver; Nandy, Andreas; Reese, Gerald

    2012-01-01

    Background The prevalence of sensitization to ragweed has risen in North America and across Europe. Although the pectate lyase Amb a 1, the major allergen of ragweed, was identified as long ago as the 1960s, little is known about the allergenicity of the 5 Amb a 1 isoallergens and other allergens present in ragweed pollen. Ragweed extracts and purified Amb a 1 isoallergens have now been characterized for their allergenic potential to determine whether a single Amb a 1 isoallergen, several isoallergens or a combination with other allergens should be included in a recombinant SIT vaccine. Methods Extracts from North American short ragweed (Ambrosia artemisiifolia) pollen were investigated by mass spectrometry (MS), 2D-PAGE and immunoblotting. Furthermore, Amb a 1 isoallergens were purified and IgE reactivity determined by immunoblotting and IgE inhibition. Results 2D-PAGE and MS of ragweed extract proved the presence of all 5 known Amb a 1 isoallergens, of which Amb a 1.01 represents the dominant form. Additionally all other ragweed allergens known by sequence (Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10) were identified. The highest IgE reactivity by immunoblotting was observed for Amb a 1.01 followed by Amb a 1.03; other Amb a 1 isoallergens as well as other detected ragweed allergens showed only weak IgE reactivity. All isoallergens with the exception of Amb a 1.04, which is only of low abundance in ragweed extract, were purified. Similar to the immunoblot analysis with crude extract, the purified isoallergens Amb a 1.02 and Amb a 1.05 showed weak IgE binding, whereas Amb a 1.01 and Amb a 1.03 had high IgE reactivity. First IgE inhibition experiments suggest that Amb a 1.01 contains all relevant IgE epitopes. Conclusions Amb a 1.01 is the most abundant Amb a 1 isoallergen, and presumably the most important ragweed allergen. However, a larger panel of ragweed-allergic subjects has to be analyzed with regard to IgE and T cell reactivities, to be

  10. The influence of European legislation on the use of diagnostic test allergens for nasal allergen provocation in routine care of patients with allergic rhinitis.

    PubMed

    Klimek, L; Hammerbacher, A S; Hellings, P W; Fokkens, W J; Hoffmann, H J; Muraro, A; Papadopoulos, N

    2015-09-01

    In patients with allergic rhinitis (AR), the nasal provocation test (NPT) is the standard procedure to evaluate the clinical response of the nasal mucosa to allergens with a high specificity and sensitivity. In AR, it is the only test that really measures the response of the diseased mucosa to allergens while skin prick test and serum IgE confirm the clinical suspicion of sensitization. Moreover, it is of special relevance in the detection of patients with Local Allergic Rhinitis (LAR), where general sensitization cannot be measured. For the evaluation of therapeutic interventions, NPT has been used for the clinical monitoring of antiallergic drugs and allergen specific immunotherapy. Legislation within the European Union (EU) defines allergens used for diagnostic tests like NPT to be medicinal products according to Directive 2001/83 EC, but national law is considering these products to be medicinal devices in a number of EU countries. Thus, NPT products are governed by different legislations and therefore standards throughout the EU. In consequence, allergens used for diagnostic purposes need different registrations and Marketing Authorization by national authorities. After a transition period, regulations of EU Directives are to be implemented in national law by all member states. At the moment, most EU countries have not fully implemented these Directives, however, it can be expected that most countries will implement it and enforce their rules within the next years. This development has a tremendous impact on the availability of diagnostic allergens for NPT in Europe and will make make nasal provocation testing very difficult if not impossible. We describe the current situation of diagnostic allergens under the special legislative conditions in the EU with special focus on allergen products used for NPT and the consequences for the diagnosis of AR and LAR. PMID:26363167

  11. Immunosuppression in Early Postnatal Days Induces Persistent and Allergen-Specific Immune Tolerance to Asthma in Adult Mice

    PubMed Central

    Chen, Yan; Zhang, Jin; Lu, Yong; Wang, Libo

    2015-01-01

    Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma. PMID:25860995

  12. Immunosuppression in early postnatal days induces persistent and allergen-specific immune tolerance to asthma in adult mice.

    PubMed

    Chen, Yan; Zhang, Jin; Lu, Yong; Wang, Libo

    2015-01-01

    Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma. PMID:25860995

  13. Allergen Microarray Indicates Pooideae Sensitization in Brazilian Grass Pollen Allergic Patients

    PubMed Central

    Moreira, Priscila Ferreira de Sousa; Gangl, Katharina; Vieira, Francisco de Assis Machado; Ynoue, Leandro Hideki; Linhart, Birgit; Flicker, Sabine; Fiebig, Helmut; Swoboda, Ines; Focke-Tejkl, Margarete; Taketomi, Ernesto Akio; Valenta, Rudolf; Niederberger, Verena

    2015-01-01

    Background Grass pollen, in particular from Lolium multiflorum is a major allergen source in temperate climate zones of Southern Brazil. The IgE sensitization profile of Brazilian grass pollen allergic patients to individual allergen molecules has not been analyzed yet. Objective To analyze the IgE sensitization profile of a Brazilian grass pollen allergic population using individual allergen molecules. Methods We analyzed sera from 78 grass pollen allergic patients for the presence of IgE antibodies specific for 103 purified micro-arrayed natural and recombinant allergens by chip technology. IgE-ELISA inhibition experiments with Lolium multiflorum, Phleum pratense extracts and a recombinant fusion protein consisting of Phl p 1, Phl p 2, Phl p 5 and Phl p 6 were performed to investigate cross-reactivities. Results Within the Brazilian grass pollen allergic patients, the most frequently recognized allergens were Phl p 1 (95%), Phl p 5 (82%), Phl p 2 (76%) followed by Phl p 4 (64%), Phl p 6 (45%), Phl p 11 (18%) and Phl p 12 (18%). Most patients were sensitized only to grass pollen allergens but not to allergens from other sources. A high degree of IgE cross-reactivity between Phleum pratense, Lolium multiflorum and the recombinant timothy grass fusion protein was found. Conclusions Component-resolved analysis of sera from Brazilian grass pollen allergic patients reveals an IgE recognition profile compatible with a typical Pooideae sensitization. The high degree of cross-reactivity between Phleum pratense and Lolium multiflorum allergens suggests that diagnosis and immunotherapy can be achieved with timothy grass pollen allergens in the studied population. PMID:26067084

  14. Development of cockroach immunotherapy by the Inner-City Asthma Consortium

    PubMed Central

    Wood, Robert A.; Togias, Alkis; Wildfire, Jeremy; Visness, Cynthia M.; Matsui, Elizabeth C.; Gruchalla, Rebecca; Hershey, Gurjit; Liu, Andrew H.; O’Connor, George T.; Pongracic, Jacqueline A.; Zoratti, Edward; Little, Frederic; Granada, Mark; Kennedy, Suzanne; Durham, Stephen R.; Shamji, Mohamed H.; Busse, William W.

    2014-01-01

    Background Cockroach allergy is a key contributor to asthma morbidity in children living in urban environments. Objective We sought to document immune responses to cockroach allergen and provide direction for the development of immunotherapy for cockroach allergy. Methods Four pilot studies were conducted: (1) an open-label study to assess the safety of cockroach sublingual immunotherapy (SLIT) in adults and children; (2) a randomized, double-blind biomarker study of cockroach SLIT versus placebo in adults; (3) a randomized, double-blind biomarker study of 2 doses of cockroach SLIT versus placebo in children; and (4) an open-label safety and biomarker study of cockroach subcutaneous immunotherapy (SCIT) in adults. Results The adult SLIT trial (n = 54; age, 18–54 years) found a significantly greater increase in cockroach-specific IgE levels between the active and placebo groups (geometric mean ratio, 1.92; P < .0001) and a trend toward increased cockroach-specific IgG4 levels in actively treated subjects (P = .09) but no evidence of functional blocking antibody response. The pediatric SLIT trial (n = 99; age, 5–17 years) found significant differences in IgE, IgG, and IgG4 responses between both active groups and the placebo group but no consistent differences between the high- and low-dose groups. In the SCIT study the treatment resulted in significant changes from baseline in cockroach IgE, IgG4, and blocking antibody levels. The safety profile of cockroach immunotherapy was reassuring in all studies. Conclusions The administration of cockroach allergen by means of SCIT is immunologically more active than SLIT, especially with regard to IgG4 levels and blocking antibody responses. No safety concerns were raised in any age group. These pilot studies suggest that immunotherapy with cockroach allergen is more likely to be effective with SCIT. PMID:24184147

  15. Immunotherapy of Melanoma.

    PubMed

    Snyder, Alexandra; Zamarin, Dmitriy; Wolchok, Jedd D

    2015-01-01

    The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma. PMID:26376963

  16. Immunotherapy in prostate cancer.

    PubMed

    Sobol, Ilya; Thompson, R H; Dong, Haidong; Krco, Christopher; Kwon, Eugene D

    2015-06-01

    Immunotherapy for the treatment of malignant neoplasms has made significant progress over the last 20 years. Multiple molecular targets and clinical agents have been developed recently, particularly in the field of metastatic adenocarcinoma of the prostate. Sipuleucel-T is currently the only FDA approved immunotherapy for prostate cancer. PSA-TRICOM (Prostvac) currently has a phase III randomized trial underway after a phase II trial showed an improvement in overall survival. Interestingly, both these agents showed improvement in overall survival with no measurable change in disease state, leading to significant controversy as the utility of these agents in prostate cancer. Ipilimumab revealed a benefit for a sub-cohort of men in a post-docetaxel group and is currently undergoing investigation in a pre-docetaxel group. There are a number of other targets such as PD-1 which have shown effectiveness in other neoplasms that will likely be investigated in the future for use in prostate cancer. PMID:25894495

  17. Immunotherapy in Peripheral Neuropathies.

    PubMed

    Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina

    2016-01-01

    Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms. PMID:26602549

  18. Bladder cancer immunotherapy.

    PubMed

    Lamm, D L; Thor, D E; Stogdill, V D; Radwin, H M

    1982-11-01

    A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. In addition, 9 patients at high risk for tumor recurrence were treated with bacillus Calmette-Guerin produced a self-limited cystitis and 1 complication (hydronephrosis) of immunotherapy was observed. Of the 57 randomized patients 54 were followed for 3 to 30 months. Tumor recurrence was documented in 13 of 26 controls (50 per cent) and only 6 of 28 patients (21 per cent) treated with bacillus Calmette-Guerin (p equals 0.027, chi-square). The interval free of disease was prolonged significantly with bacillus Calmette-Guerin treatment (p equals 0.014, generalized Wilcoxon test). Importantly, a simple purified protein derivative skin test distinguished those patients who responded to bacillus Calmette-Guerin immunotherapy from those who did not. Only 1 of 17 treated patients (6 per cent) whose purified protein derivative test converted from negative to positive had tumor recurrence compared to 5 recurrences (38 per cent) among the 13 patients whose test remained negative or had been positive before treatment (p equals 0.022, chi-square). Bacillus Calmette-Guerin was given to 10 patients with stage B transitional cell carcinoma who were not candidates for cystectomy and 7 are free of disease. Of 5 patients with carcinoma in situ 3 remain free of tumor after bacillus Calmette-Guerin treatment and 5 of 6 who had multiple recurrences after intravesical chemotherapy responded favorably to bacillus Calmette-Guerin immunotherapy. PMID:6757467

  19. Immunotherapy of Fungal Infections.

    PubMed

    Datta, Kausik; Hamad, Mawieh

    2015-11-01

    Fungal organisms are ubiquitous in the environment. Pathogenic fungi, although relatively few in the whole gamut of microbial pathogens, are able to cause disease with varying degrees of severity in individuals with normal or impaired immunity. The disease state is an outcome of the fungal pathogen's interactions with the host immunity, and therefore, it stands to reason that deep/invasive fungal diseases be amenable to immunotherapy. Therefore, antifungal immunotherapy continues to be attractive as an adjunct to the currently available antifungal chemotherapy options for a number of reasons, including the fact that existing antifungal drugs, albeit largely effective, are not without limitations, and that morbidity and mortality associated with invasive mycoses are still unacceptably high. For several decades, intense basic research efforts have been directed at development of fungal immunotherapies. Nevertheless, this approach suffers from a severe bench-bedside disconnect owing to several reasons: the chemical and biological peculiarities of the fungal antigens, the complexities of host-pathogen interactions, an under-appreciation of the fungal disease landscape, the requirement of considerable financial investment to bring these therapies to clinical use, as well as practical problems associated with immunizations. In this general, non-exhaustive review, we summarize the features of ongoing research efforts directed towards devising safe and effective immunotherapeutic options for mycotic diseases, encompassing work on antifungal vaccines, adoptive cell transfers, cytokines, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), and other agents. PMID:26575463

  20. 12 Comprehensive Detection of Allergens in Grass Pollen Extracts by Mass Spectrometry

    PubMed Central

    Augustin, Steffen; Mitulski, Liane; Cromwell, Oliver; Reese, Gerald; Nandy, Andreas

    2012-01-01

    Background More than 40% of type 1-allergic individuals suffer from hypersensitivity to grass pollen. Patients are treated traditionally with specific immunotherapy using pollen extracts derived from one or several different Pooideae species. While for several species the most important allergens (group 1 and group 5) have been identified, other allergens have either not been identified or sequence data are still missing. We have used mass spectrometry (MS) together with genetic and immunological methods to identify allergens in various grass pollen extracts. Methods Pollen extracts of 6 different grass species (Phleum pratense, Holcus lanatus, Lolium perenne, Dactylus glomerata, Festuca pratensis, Poa pratensis) and a mixture thereof were analyzed. For identification of allergens by MS, extracts were subjected to enzymatic digestion. Resulting peptides were separated by liquid chromatography and analyzed by tandem mass spectrometry. Protein identification was performed by searching both the NCBIPlant release and an individually designed database. The presence of individual allergens was confirmed with allergen-specific monoclonal antibodies. Unknown sequences were determined following cDNA synthesis from pollen RNA and allergen sequence amplification by PCR. Results Fes p 1 and Fes p 5 were identified by the PCR approach. MS analysis of pollen extracts from the 6 individual species resulted in detection of all known allergens including the newly identified Fes p 1 and Fes p 5. Based on the homology of allergens from different grass species, previously unknown sequences of representatives of groups 2, 3, 4, 7, 11, 12 and 13 were detected by MS in investigated extracts with high sequence coverage. Group 6 allergens could not be identified in some of the analyzed extracts. These findings are supported by immunological analyses and thus demonstrate the specificity of the applied method. Members of all allergen groups were identified in an extract mix prepared from

  1. A novel IgE-binding epitope of cat major allergen, Fel d 1.

    PubMed

    Tasaniyananda, Natt; Tungtrongchitr, Anchalee; Seesuay, Watee; Sakolvaree, Yuwaporn; Indrawattana, Nitaya; Chaicumpa, Wanpen; Sookrung, Nitat

    2016-02-12

    Information on the antigenic repertoire, especially the IgE-binding epitopes of an allergen is important for understanding the allergen induced immune response and cross-reactivity, as well as for generating the hypoallergenic variants for specific component resolved immunotherapy/diagnosis (CRIT and CRD). Data on the IgE-binding epitopes of cat allergens are scarce. In this study, a novel IgE-binding epitope of the cat major allergen, Fel d 1, was identified. Mouse monoclonal antibody (MAb) specific to the Fel d 1 was produced. Computerized intermolecular docking was used for determining the residues of the Fel d 1 bound by the specific MAb. The presumptive surface exposed residues of the Fel d 1 intrigued by the MAb are located on the chain 1. They are: L34 and T37 (helix 1); T39 (between helices 1 and 2); P40, E42 and E45 (helix 2); R61, K64, N65 and D68 (helix 3); and E73 and K76 (helix 4). The MAb competed efficiently with the cat allergic patients' serum IgE for Fel d 1 binding in the competitive IgE binding assay, indicating allergenicity of the MAb epitope. The newly identified allergenic epitope of the Fel d 1 is useful in a design of the CRIT and CRD for cat allergy. PMID:26797272

  2. CTLA-4 recombinant protein genetically fused to canine Fcepsilon receptor Ialpha enhances allergen specific lymphocyte responses in experimentally sensitized dogs.

    PubMed

    Yasunaga, Sho; Tsukui, Toshihiro; Masuda, Kenichi; Ohno, Koichi; Tsujimoto, Hajime

    2004-06-01

    Vaccination with a recombinant antigen fused to a targeting molecule is a potential strategy for inducing efficient immune responses. For the therapeutic purpose of allergic diseases in dogs, a DNA construct which expresses recombinant fusion protein with two functional domains, cytotoxic T lymphocyte antigen (CTLA-4) and Fcepsilon receptor Ialpha, was developed to bridge antigen-presenting cells and IgE-allergen complex. The recombinant fusion protein expressed by the DNA construct was demonstrated to retain the ability to bind monocytes in PBMC and dog IgE, respectively. Additionally, the recombinant protein induced enhancement of allergen-induced lymphoproliferation in experimentally sensitized dogs under conditions of suboptimal allergen stimulation. These results indicated that the DNA construct could enhance allergen-induced immune responses in vivo, implying its usefulness for perspective application in immunotherapy in dogs. PMID:15240934

  3. [Evaluation of the pediatric aspects of the WHO document and meta-analysis of immunotherapy].

    PubMed

    Ibáñez Sendín, M D

    2000-01-01

    In spite of the existence of numerous scientific studies on the beneficial effect of immunotherapy with specific allergens in the treatment of allergic diseases, their results have not been easily accepted as the methodology and the valuation of the studies have been very heterogeneous. Over the last few years the meta-analysis technology has been developed as a useful tool to globally value the results on the different research studies related to a specific problem. When meta-analyse are carried out correctly, they are accepted as an optimum way to express the results obtained from the different studies from a common view point. In 1995 Abramson MJ, Puy RM and Weiner INI published the first meta-analysis on the efficiency of immunotherapy with specific allergens in the treatment of asthma. The same authors continued to carry out systematic reviews of this theme, and their results were published in the Cochrane Library Document. In october 1999 the latest meta-analysis on immunotherapy in asthma, also carried out by Abramson et al was published in Allergy. In this study 62 investigations published from 1954 to 1998 were included. None of the meta-analyses published to date have separately analysed the studies carried out on children, nor have special considerations been made with respect to the 105 patients who were of paediatric age. The first meta-analysis studies, as well as the ones carried out in 1999, only value random clinical tests, in which there is a valuation of the evolution of asthma and in which mite, pollen, animal, fungi or epithelial allergenic vaccinations are used. Only the subcutaneous administration of the vaccine was allowed. Although this meta-analysis has not been designed to obtain specific conclusions of the effectiveness of immunotherapy in children, probably of conclusions of some of the sections can be applied to the children and/or adolescent population. The authors point out, by valuing the results of the effect of immunotherapy on

  4. The Heterogeneity of Oral Immunotherapy Clinical Trials: Implications and Future Directions.

    PubMed

    Yee, Christina S K; Rachid, Rima

    2016-04-01

    Food allergy is a potentially life-threatening disease which affects up to 8% of children and 2-3% of adults. Increasing food allergy prevalence poses a major public health concern. Induction of desensitization to food allergens through oral immunotherapy (OIT) is an expanding area of study encompassing peanut, egg, milk, and other food allergens. OIT consists of administering incremental doses of food allergen to food-allergic patients, to induce a state of desensitization. Safety, tolerability, and efficacy all remain ongoing concerns. Clinical trials for oral immunotherapy have encompassed many variations, including differences in dosage sizes and frequency, duration of build-up, type of allergen used, patient characteristics, and adjuvant therapies. Consequently, studies have also shown variation in rates of adverse effects, and successful desensitization. Here, we provide an overview of the key studies and discuss the implications of this heterogeneity. While desensitization is successful in the majority of patients, only a minority appear to develop sustained unresponsiveness even after years of therapy. Much larger and longitudinal studies using more homogenous protocols are needed in order to evaluate the clinical applicability of OIT, its long-term effectiveness, and effect on quality of life. The role of adjunctive therapies, including omalizumab and probiotics, requires further evaluation. PMID:26922433

  5. Nonspecific plasma proteins during sublingual immunotherapy.

    PubMed

    Reich, M; Zwacka, G; Markert, U R

    2003-01-01

    Usually, specific allergy-related plasma proteins such as immunoglobulin E (IgE) and immunoglobulin G (IgG) are used for estimating the grade of sensitization and follow-up of immunotherapy. In recent years, several nonspecific inflammatory markers, such as sICAM-1 and sIL-2R, have been shown as being suitable for therapy control in allergy. In our investigation of patients under sublingual immunotherapy (SLIT), plasma from 42 healthy controls and 133 children with single inhalation allergies to grass pollen, birch pollen or house dust mites was obtained during the symptom-free period. Patients showed symptoms including allergic rhinitis, dermatitis and allergic asthma with one single RAST class 3 or higher. Plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), sE-selectin, interleukin-12 (IL-12) and specific IgG4 were analyzed with the ELISA technique. After 1 year of SLIT, concentrations of sICAM-1, sIL-2R and sE-selectin declined significantly when results from all patients were taken as one group. Regarding the single allergen groups, the sICAM-1 and sIL-2R decrease was significant in the grass and mite group, but not in the birch group, while the sE-selectin decline was only significant in the birch group after 1 year of SLIT, but not in the grass and the mite group. No difference was observed in IL-12 and IgG4 expression. In two groups of controls with a mean age of 9.5 versus 17.5 years, the analyzed parameters were not age-dependent. The increased proteins may be useful as additional markers for the evaluation of immunological effects and follow-up investigations of allergy therapies. PMID:12947996

  6. Production and immunological analysis of IgE reactive recombinant egg white allergens expressed in Escherichia coli.

    PubMed

    Dhanapala, Pathum; Doran, Tim; Tang, Mimi L K; Suphioglu, Cenk

    2015-05-01

    IgE-mediated allergy to chicken egg affects a large number of children and adults worldwide. The current management strategy for egg allergy is strict avoidance, however this is impractical due to the presence of eggs in a range of foods and pharmaceutical products including vaccines. Strict avoidance also poses nutritional disadvantages due to high nutritional value of eggs. Allergen specific immunotherapy is being pursued as a curative treatment, in which an allergic individual is gradually exposed to the allergen to induce tolerance. Use of recombinant proteins for immunotherapy has been beneficial due to the purity of the recombinant proteins compared to natural proteins. In this study, we produced IgE reactive recombinant egg white proteins that can be used for future immunotherapy. Using E. coli as an expression system, we successfully produced recombinant versions of Gal d 1, 2 and 3, that were IgE reactive when tested against a pool of egg allergic patients' sera. The IgE reactivity indicates that these recombinant proteins are capable of eliciting an immune response, thus being potential candidates for immunotherapy. We have, for the first time, attempted to produce recombinant versions of all 4 major egg white allergens in E. coli, and successfully produced 3, with only Gal d 4 showing loss of IgE reactivity in the recombinant version. The results suggest that egg allergy in Australian populations may mainly be due to IgE reactivity to Gal d 3 and 4, while Gal d 1 shows higher IgE reactivity. This is the first report of a collective and comparative immunological analysis of all 4 egg white allergens. The significance of this study is the potential use of the IgE reactive recombinant egg white proteins in immunotherapy to treat egg allergic patients. PMID:25656803

  7. PAUCam readout electronics assembly, integration and test (AIT)

    NASA Astrophysics Data System (ADS)

    Jiménez, Jorge; Illa, José M.; Cardiel-Sas, Laia; de Vicente, Juan; Castilla, Javier; Casas, Ricard

    2014-08-01

    The PAUCam is an optical camera with an array of 18 CCDs (Hamamatsu Photonics K.K.) and up to 45 narrow and broad band filters. The camera will be installed on the William Herschel Telescope (WHT) in the Canary Islands, Spain. In order to fulfill with the specifications for the camera readout system, it was necessary to test the different readout electronics subsystems individually before to integrate the final readout work package, which is composed of 4 MONSOON (NOAO) front-ends, 6 fan out boards (MIX), each one driving up to 5 CCDs signals and a pre-amplification stage (PREAMP) located inside the cryostat. To get the subsystems integration, it was built a small camera prototype using the same technology as used in the main camera: a carbon fiber cryostat refrigerated by a cryotiger cooling system but with capacity to allocate just 2 CCDs, which were readout and re-characterized to measure the electronics performance as conversion factor or gain, readout noise, stability, linearity, etc. while the cross-talk was measured by using a spot-light. The aim of this paper is to review the whole process of assembly, integration and test (AIT) of the readout electronics work package and present the main results to demonstrate the viability of the proposed systems to be use with the PAUCam camera.

  8. Identification of Novel Short Ragweed Pollen Allergens Using Combined Transcriptomic and Immunoproteomic Approaches

    PubMed Central

    Bouley, Julien; Groeme, Rachel; Jain, Karine; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent; Moingeon, Philippe

    2015-01-01

    Background Allergy to short ragweed (Ambrosia artemisiifolia) pollen is a serious and expanding health problem in North America and Europe. Whereas only 10 short ragweed pollen allergens are officially recorded, patterns of IgE reactivity observed in ragweed allergic patients suggest that other allergens contribute to allergenicity. The objective of the present study was to identify novel allergens following extensive characterization of the transcriptome and proteome of short ragweed pollen. Methods Following a Proteomics-Informed-by-Transcriptomics approach, a comprehensive transcriptomic data set was built up from RNA-seq analysis of short ragweed pollen. Mass spectrometry-based proteomic analyses and IgE reactivity profiling after high resolution 2D-gel electrophoresis were then combined to identify novel allergens. Results Short ragweed pollen transcripts were assembled after deep RNA sequencing and used to inform proteomic analyses, thus leading to the identification of 573 proteins in the short ragweed pollen. Patterns of IgE reactivity of individual sera from 22 allergic patients were assessed using an aqueous short ragweed pollen extract resolved over 2D-gels. Combined with information derived from the annotated pollen proteome, those analyses revealed the presence of multiple unreported IgE reactive proteins, including new Amb a 1 and Amb a 3 isoallergens as well as 7 novel candidate allergens reacting with IgEs from 20–70% of patients. The latter encompass members of the carbonic anhydrase, enolase, galactose oxidase, GDP dissociation inhibitor, pathogenesis related-17, polygalacturonase and UDP-glucose pyrophosphorylase families. Conclusions We extended the list of allergens identified in short ragweed pollen. These findings have implications for both diagnosis and allergen immunotherapy purposes. PMID:26317427

  9. Immunotherapies in rheumatologic disorders.

    PubMed

    Miller, Anne V; Ranatunga, Sriya K M

    2012-05-01

    Over the past several decades, rheumatology has directed its focus to understanding and countering the immune dysregulation underlying autoimmune diseases with rheumatologic manifestations. Older therapies, effective though poorly understood, are being scrutinized anew and are yielding the immune-modulating mechanisms behind their efficacy. New therapies, the "biologics," are drugs tailored to address specific immune defects and imbalances. This article discusses the current standard and biologic immunotherapies of the rheumatic diseases, correlating our current understanding of their mechanisms with dysfunctions believed to be present in the major autoimmune syndromes, especially rheumatoid arthritis and systemic lupus erythematosus. PMID:22703852

  10. [Immunotherapy for Alzheimer's disease].

    PubMed

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID:26815584

  11. Stability of patch test allergens.

    PubMed

    Joy, Nicole Marie; Rice, Kristen R; Atwater, Amber Reck

    2013-01-01

    Patch testing is widely used in evaluating suspected contact dermatitis. One major component of a quality patch test result is a dependable, predictable allergen supply. The allergen needs to be present at a sufficient concentration to elicit a reaction in an allergic patient. To better understand the stability of patch-test allergens, we completed a systematic review of the literature. We found that there is variability in stability among patch-test allergens and that although a few have been shown to be stable, many degrade when in storage. In most cases, expiration dates should be honored. In addition, allergen panels should be prepared as close to the time of patch test application as is possible. PMID:24030367

  12. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant

    PubMed Central

    Petrarca, Claudia; Clemente, Emanuela; Toto, Valentina; Iezzi, Manuela; Rossi, Cosmo; Zanotta, Stefania; Mistrello, Gianni; Zanoni, Ivan; Granucci, Francesca; Arioli, Stefania; Mora, Diego; Guglielmetti, Simone; Paganelli, Roberto; Di Gioacchino, Mario

    2014-01-01

    Lactobacilli are able to induce upregulation of co-stimulatory molecules in DCs with Th1 cytokines production and increase in Treg activity. This could explain the observed effectiveness of the prolonged administration of lactobacilli in the prevention of allergic disorders in infants and envisage the possible use of bacteria expressing the allergen for the specific immunotherapy of allergic diseases. Hence, we evaluated Streptococcus thermophilus (ST) expressing rBet v 1 as allergen delivery tool and adjuvant factor for immunotherapy in Betv1-sensitized mice. rBet v 1 gene was introduced and expressed in ST (ST[rBet v 1]). BALB/c mice were sensitized with rBet v 1 and then treated with either ST alone, ST[rBet v 1], or the combination of ST and rBet v 1, for 20 days. After 2 aerosol challenges, Treg frequency, in vitro allergen-induced cytokines, rBet v 1-specific IgE and IgG2a, and bronchial histology were made in harvested spleen, sera, and lung. Results were compared with those obtained from not-treated/sensitized mice. ST[rBet v 1] induced immunological and histological changes typical of successful SIT: increased frequency of Tregs and expression of Foxp3; decreased allergen-specific IgE/IgG2a ratio; decrease of in vitro rBet v 1-induced IL-4 from spleen cells; increased allergen-induced IL-10 and IFN-γ; drop of bronchial eosinophilia. ST and ST+rBet v 1 combination, even though induced a slight increase in the frequency of Tregs and moderate allergen-induced IL-10, were ineffective in reducing bronchial eosinophilia, allergen induced IL-4 and rBet v 1-specific IgE/IgG2a ratio. ST[rBet v 1] has tolerogenic and Th-1 skewing properties and efficiently delivers the allergen to the gut immune-system restraining and readdressing the established specific Th2 response toward the allergen in mice. PMID:24603094

  13. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant.

    PubMed

    Petrarca, Claudia; Clemente, Emanuela; Toto, Valentina; Iezzi, Manuela; Rossi, Cosmo; Zanotta, Stefania; Mistrello, Gianni; Zanoni, Ivan; Granucci, Francesca; Arioli, Stefania; Mora, Diego; Guglielmetti, Simone; Paganelli, Roberto; Di Gioacchino, Mario

    2014-01-01

    Lactobacilli are able to induce upregulation of co-stimulatory molecules in DCs with Th1 cytokines production and increase in Treg activity. This could explain the observed effectiveness of the prolonged administration of lactobacilli in the prevention of allergic disorders in infants and envisage the possible use of bacteria expressing the allergen for the specific immunotherapy of allergic diseases. Hence, we evaluated Streptococcus thermophilus (ST) expressing rBet v 1 as allergen delivery tool and adjuvant factor for immunotherapy in Betv1-sensitized mice. rBet v 1 gene was introduced and expressed in ST (ST[rBet v 1]). BALB/c mice were sensitized with rBet v 1 and then treated with either ST alone, ST[rBet v 1], or the combination of ST and rBet v 1, for 20 days. After 2 aerosol challenges, Treg frequency, in vitro allergen-induced cytokines, rBet v 1-specific IgE and IgG2a, and bronchial histology were made in harvested spleen, sera, and lung. Results were compared with those obtained from not-treated/sensitized mice. ST[rBet v 1] induced immunological and histological changes typical of successful SIT: increased frequency of Tregs and expression of Foxp3; decreased allergen-specific IgE/IgG2a ratio; decrease of in vitro rBet v 1-induced IL-4 from spleen cells; increased allergen-induced IL-10 and IFN-γ; drop of bronchial eosinophilia. ST and ST+rBet v 1 combination, even though induced a slight increase in the frequency of Tregs and moderate allergen-induced IL-10, were ineffective in reducing bronchial eosinophilia, allergen induced IL-4 and rBet v 1-specific IgE/IgG2a ratio. ST[rBet v 1] has tolerogenic and Th-1 skewing properties and efficiently delivers the allergen to the gut immune-system restraining and readdressing the established specific Th2 response toward the allergen in mice. PMID:24603094

  14. Current status of immunotherapy.

    PubMed

    Suzuki, Susumu; Ishida, Takashi; Yoshikawa, Kazuhiro; Ueda, Ryuzo

    2016-03-01

    The successful use of immune checkpoint inhibitors has been big breakthrough in the development of cancer immunotherapy. Anti-CTLA-4 monoclonal antibody, ipilimumab, is the first-approved immune checkpoint inhibitor and has shown durable objective responses for advanced melanoma beyond the effect of dacarbazine. Anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, are other immune checkpoint inhibitors that have demonstrated more effective results than conventional drugs in clinical trials for a variety of advanced solid tumors including melanoma, non-small cell lung carcinoma and renal carcinoma. These studies have indicated that the enhancement of anti-cancer immunity by controlling the immune suppressive environment in cancer tissues is an important issue for the development of cancer immune-therapy. Accordingly, in recent years, the enthusiasm for research of cancer immunology has shifted to studies regarding the formation of the immune suppressive environment, immune suppression mechanisms in cancer tissues and the molecules and cells involved in these pathways. Novel findings from these studies might lead to the development of cancer immunotherapy based on control of the immune suppressive environment. PMID:26819277

  15. Taxonomy of Allergenic Fungi.

    PubMed

    Levetin, Estelle; Horner, W Elliott; Scott, James A

    2016-01-01

    The Kingdom Fungi contains diverse eukaryotic organisms including yeasts, molds, mushrooms, bracket fungi, plant rusts, smuts, and puffballs. Fungi have a complex metabolism that differs from animals and plants. They secrete enzymes into their surroundings and absorb the breakdown products of enzyme action. Some of these enzymes are well-known allergens. The phylogenetic relationships among fungi were unclear until recently because classification was based on the sexual state morphology. Fungi lacking an obvious sexual stage were assigned to the artificial, now-obsolete category, "Deuteromycetes" or "Fungi Imperfecti." During the last 20 years, DNA sequencing has resolved 8 fungal phyla, 3 of which contain most genera associated with important aeroallergens: Zygomycota, Ascomycota, and Basidiomycota. Advances in fungal classification have required name changes for some familiar taxa. Because of regulatory constraints, many fungal allergen extracts retain obsolete names. A major benefit from this reorganization is that specific immunoglobulin E (IgE) levels in individuals sensitized to fungi appear to closely match fungal phylogenetic relationships. This close relationship between molecular fungal systematics and IgE sensitization provides an opportunity to systematically look at cross-reactivity and permits representatives from each taxon to serve as a proxy for IgE to the group. PMID:26725152

  16. Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines.

    PubMed

    Manzano, Ana I; Javier Cañada, F; Cases, Bárbara; Sirvent, Sofia; Soria, Irene; Palomares, Oscar; Fernández-Caldas, Enrique; Casanovas, Miguel; Jiménez-Barbero, Jesús; Subiza, José L

    2016-02-01

    Immunotherapy for treating IgE-mediated allergies requires high doses of the corresponding allergen. This may result in undesired side effects and, to avoid them, hypoallergenic allergens (allergoids) polymerized with glutaraldehyde are commonly used. Targeting allergoids to dendritic cells to enhance cell uptake may result in a more effective immunotherapy. Allergoids coupled to yeast mannan, as source of polymannoses, would be suitable for this purpose, since mannose-binding receptors are expressed on these cells. Conventional conjugation procedures of mannan to proteins use oxidized mannan to release reactive aldehydes able to bind to free amino groups in the protein; yet, allergoids lack these latter because their previous treatment with glutaraldehyde. The aim of this study was to obtain allergoids conjugated to mannan by an alternative approach based on just glutaraldehyde treatment, taking advantage of the mannoprotein bound to the polymannose backbone. Allergoid-mannan glycoconjugates were produced in a single step by treating with glutaraldehyde a defined mixture of allergens derived from Phleum pratense grass pollen and native mannan (non-oxidized) from Saccharomyces cerevisae. Analytical and structural studies, including 2D-DOSY and (1)H-(13)C HSQC nuclear magnetic resonance spectra, demonstrated the feasibility of such an approach. The glycoconjugates obtained were polymers of high molecular weight showing a higher stability than the native allergen or the conventional allergoid without mannan. The allergoid-mannan glycoconjugates were hypoallergenic as detected by the IgE reactivity with sera from grass allergic patients, even with lower reactivity than conventional allergoid without mannan. Thus, stable hypoallergenic allergoids conjugated to mannan suitable for using in immunotherapy can be achieved using glutaraldehyde. In contrast to mannan oxidation, the glutaraldehyde approach allows to preserve mannoses with their native geometry, which may be

  17. Mouse Models of Tumor Immunotherapy.

    PubMed

    Ngiow, Shin Foong; Loi, Sherene; Thomas, David; Smyth, Mark J

    2016-01-01

    Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials. In this review, we will discuss the major classes of experimental mouse models of cancer commonly used for immunotherapy assessment and provide examples to guide the selection of appropriate models. We present some new data concerning the utility of a carcinogen-induced tumor model for comparing immunotherapies and combining immunotherapy with chemotherapy. We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients. PMID:26922998

  18. Immunotherapy for metastatic prostate cancer

    PubMed Central

    Drake, Charles G.

    2016-01-01

    Chemotherapy with docetaxel is the standard treatment for men with metastatic prostate cancer, and results in statistically significant improvements in survival, as well as in quality of life. However, the response rate to single-agent docetaxel is approximately 40% to 45%, emphasizing a need for alternative approaches. More significantly, with the onset of early, PSA-based detection of prostate cancer and closer follow-up, many men present with metastatic disease that remains asymptomatic. For such patients, the side effects of chemotherapy would compromise their current performance status and, thus, a nontoxic, early treatment option that could improve overall survival would be highly desirable. Immunotherapy represents one such approach; a number of clinical trials have suggested a survival benefit for immunotherapy in metastatic prostate cancer and confirmed that these agents are generally well-tolerated. As is the case for chemotherapy, it is doubtful that maximal survival benefit will be achieved with single-agent immunotherapy; experimental treatments in which mechanistically distinct immunotherapy approaches are combined, as well as approaches in which immunotherapy is combined with chemotherapy or hormonal therapy are currently under investigation. This review will discuss the mechanisms of action of several immunotherapy approaches for metastatic prostate cancer, focusing on active immunotherapy as opposed to administration of anti-tumor antibodies. The relative advantages and disadvantages of current approaches will be noted, and ongoing clinical trials will be highlighted. PMID:18593624

  19. Modified immunotherapy for alopecia areata.

    PubMed

    Yoshimasu, Takashi; Furukawa, Fukumi

    2016-07-01

    Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently high recommended sensitization dose of 1%-2% SADBE, often decreasing patient compliance. We assessed a modified immunotherapy for AA using SADBE at a starting concentration of 0.01% without sensitization. After one or two weeks of initial 0.01% SADBE application, the concentration of SADBE was increased gradually to 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 1% and 2% until the patients felt itching or erythema at the AA lesion site. The modified immunotherapy showed a response rate of 69.4% (25/36), equivalent to conventional immunotherapy using SADBE starting at 1%-2% sensitization. Furthermore, we investigated the combination therapy of SADBE and multiple courses of steroid pulses for AA. The response rate for combination therapy was 73.7% (28/38); however, the group receiving combination therapy showed a significant prevalence of severe AA compared with the group receiving modified immunotherapy only. We reviewed the efficacy and safety of modified immunotherapy without initial sensitization and combination therapy with immunotherapy and multiple courses of pulses for AA. PMID:26932732

  20. Allergen-induced airway responses.

    PubMed

    Gauvreau, Gail M; El-Gammal, Amani I; O'Byrne, Paul M

    2015-09-01

    Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1-3 h, and late responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over 6-12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose. PMID:26206871

  1. Aluminium adjuvants and adverse events in sub-cutaneous allergy immunotherapy

    PubMed Central

    2014-01-01

    Sub-cutaneous immunotherapy is an effective treatment for allergy. It works by helping to modify or re-balance an individual’s immune response to allergens and its efficacy is greatly improved by the use of adjuvants, most commonly, aluminium hydroxide. Aluminium salts have been used in allergy therapy for many decades and are assumed to be safe with few established side-effects. This assumption belies their potency as adjuvants and their potential for biological reactivity both at injection sites and elsewhere in the body. There are very few data purporting to the safety of aluminium adjuvants in allergy immunotherapy and particularly so in relation to longer term health effects. There are, if only few, published reports of adverse events following allergy immunotherapy and aluminium adjuvants are the prime suspects in the majority of such incidents. Aluminium adjuvants are clearly capable of initiating unwanted side effects in recipients of immunotherapy and while there is as yet no evidence that such are commonplace it is complacent to consider aluminium salts as harmless constituents of allergy therapies. Future research should establish the safety of the use of aluminium adjuvants in sub-cutaneous allergy immunotherapy. PMID:24444186

  2. Mass spectrometric investigation of molecular variability of grass pollen group 1 allergens.

    PubMed

    Fenaille, François; Nony, Emmanuel; Chabre, Henri; Lautrette, Aurélie; Couret, Marie-Noëlle; Batard, Thierry; Moingeon, Philippe; Ezan, Eric

    2009-08-01

    Natural grass pollen allergens exhibit a wide variety of isoforms. Precise characterization of such microheterogeneity is essential to improve diagnosis and design appropriate immunotherapies. Moreover, standardization of allergen vaccine production is a prerequisite for product safety and efficiency. Both qualitative and quantitative analytical methods are thus required to monitor and control the huge natural variability of pollens, as well as final product quality. A proteomic approach has been set up to investigate in depth the structural variability of five group 1 allergens originating from distinct grass species (Ant o 1, Dac g 1, Lol p 1, Phl p 1, and Poa p 1). Whereas group 1 is the most conserved grass pollen allergen, great variations were shown between the various isoforms found in these five species using mass spectrometry, with many amino acid exchanges, as well as variations in proline hydroxylation level and in main N-glycan motifs. The presence of O-linked pentose residues was also demonstrated, with up to three consecutive units on the first hydroxyproline of Ant o 1. In addition, species-specific peptides were identified that might be used for product authentication or individual allergen quantification. Lastly, natural or process-induced modifications (deamidation, oxidation, glycation) were evidenced, which might constitute useful indicators of product degradation. PMID:19572759

  3. Expression, purification and characterization of Der f 27, a new allergen from dermatophagoides farinae

    PubMed Central

    Lin, Jianli; Li, Meng; Liu, Yulin; Jiang, Congli; Wu, Yulan; Wang, Yuanyuan; Gao, Anjian; Liu, Zhigang; Yang, Pingchang; Liu, Xiaoyu

    2016-01-01

    The house dust mite (HDM), Dermatophagoidesfarinae (D. farina), is one of the most important indoor allergen sources and a major elicitor of allergic asthma; itscharacterization is important in the diagnosis and immunotherapy of mite allergen-relevant diseases. This study aims to characterize a novel allergen, the D. farinaederived serpin (Der f 27). In this study, the total RNA of D. farinae was extracted, and the Der f 27 gene was cloned and expressed. The allergenicity of recombinant Der f 27 protein was determined by enzyme-linked immunosorbent assay, and Western-blotting with the sera of asthma patients, and skin prick test (SPT) in allergic human subjects. A r-Der f 27 allergic asthma mouse model was established. The cloned Der f 27 gene has been presented at the Gene Bank with an accession number of KM009995. The IgE levels of r-Der f 27 in the serum from r-Der f 27 SPT positive allergic patients were 3 folds more than healthy subjects. The Der f 27 SPT positive ratewas 42.1% in 19 DM-SPT positive patients. Airway hyperresponsiveness, serum specific IgE, and levels of interleukin-4 in the spleen cell culture supernatant were significantly increased in allergic asthma mice sensitized to r-Der f 27. In conclusion, Der f 27 is a new subtype of house mite allergen. PMID:27347356

  4. Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen.

    PubMed

    Groeme, Rachel; Airouche, Sabi; Kopečný, David; Jaekel, Judith; Savko, Martin; Berjont, Nathalie; Bussieres, Laetitia; Le Mignon, Maxime; Jagic, Franck; Zieglmayer, Petra; Baron-Bodo, Véronique; Bordas-Le Floch, Véronique; Mascarell, Laurent; Briozzo, Pierre; Moingeon, Philippe

    2016-06-17

    Allergy to the short ragweed (Ambrosia artemisiifolia) pollen is a major health problem. The ragweed allergen repertoire has been recently expanded with the identification of Amb a 11, a new major allergen belonging to the cysteine protease family. To better characterize Amb a 11, a recombinant proform of the molecule with a preserved active site was produced in Escherichia coli, refolded, and processed in vitro into a mature enzyme. The enzymatic activity is revealed by maturation following an autocatalytic processing resulting in the cleavage of both N- and C-terminal propeptides. The 2.05-Å resolution crystal structure of pro-Amb a 11 shows an overall typical C1A cysteine protease fold with a network of molecular interactions between the N-terminal propeptide and the catalytic triad of the enzyme. The allergenicity of Amb a 11 was confirmed in a murine sensitization model, resulting in airway inflammation, production of serum IgEs, and induction of Th2 immune responses. Of note, inflammatory responses were higher with the mature form, demonstrating that the cysteine protease activity critically contributes to the allergenicity of the molecule. Collectively, our results clearly demonstrate that Amb a 11 is a bona fide cysteine protease exhibiting a strong allergenicity. As such, it should be considered as an important molecule for diagnosis and immunotherapy of ragweed pollen allergy. PMID:27129273

  5. The peanut allergy epidemic: allergen molecular characterisation and prospects for specific therapy.

    PubMed

    de Leon, Maria P; Rolland, Jennifer M; O'Hehir, Robyn E

    2007-01-01

    Peanut (Arachis hypogaea) allergy is a major cause of food-induced anaphylaxis, with increasing prevalence worldwide. To date, there is no cure for peanut allergy, and, unlike many other food allergies, it usually persists through to adulthood. Prevention of exposure to peanuts is managed through strict avoidance, which can be compromised by the frequent use of peanuts and peanut products in food preparations. Conventional subcutaneous-injection allergen immunotherapy using crude peanut extract is not a recommended treatment because of the risk of severe side effects, largely as a result of specific IgE antibodies. Consequently, there is an urgent need to develop a suitable peanut allergen preparation that can induce specific clinical and immunological tolerance to peanuts in allergic individuals without adverse side effects. This requires detailed molecular and immunological characterisation of the allergenic components of peanut. This article reviews current knowledge on clinically relevant peanut allergens, in particular Ara h 1, Ara h 2 and Ara h 3, together with options for T-cell-reactive but non-IgE-binding allergen variants for specific immunotherapeutic strategies. These include T-cell-epitope peptide and hypoallergenic mutant vaccines. Alternative routes of administration such as sublingual are also considered, and appropriate adjuvants for delivering effective treatments at these sites examined. PMID:17210088

  6. Tolerance and immunological changes of chemically modified allergen vaccine of Parietaria judaica in accelerated schedules.

    PubMed

    Asturias, J A; Ferrer, A; Arilla, M C; Andreu, C; Madariaga, B; Martínez, A

    2007-03-01

    The physicochemical modification of allergen vaccines provides a chance for administering higher doses in a shorter period of time. We sought to assess the safety and immunological changes of using a biologically standardized and modified Parietaria judaica pollen extract in accelerated schedules. Two accelerated schedules were tested in 45 P. judaica-allergic patients: 20 patients reached the maximum dose after two visits using two different concentrations and 25 patients reached the maximum dose after only one visit with two injections of the maximum concentration vial. The tolerance was assessed by recording all side effects related with immunotherapy. Specific antibody levels against native extract and rPar j 2 allergen were evaluated at the beginning and the end of the study. Allergenic potency determined by enzyme allergosorbent test (EAST) inhibition and skin prick test showed that modified P. judaica pollen had a 99.9% less allergenicity than native extract. After 650 doses administered, two clinically irrelevant local reactions (diameter<0 x 5 cm) and no systemic reactions were registered. Significant increases in allergen-specific IgG4 and IgG against P. judaica extract and rPar j 2 and significant decrease of specific IgE against Par j 2 were observed. The modified extract of P. judaica is safe to treat sensitive patients, even at accelerated regimens, and induces significant immunological changes. PMID:17302898

  7. Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research.

    PubMed

    North, Michelle L; Soliman, Mena; Walker, Terry; Steacy, Lisa M; Ellis, Anne K

    2015-04-01

    The aim of this study is to review advances in basic and clinical allergic rhinitis (AR) research over the past decade that have been conducted using controlled allergen challenge facility (CACF) models of allergen challenge. Databases, including PubMed, Medline, and Web of Science were searched for articles employing an ambient pollen exposure in a controlled facility to study AR, published between 2004 and the present date, using the terms as follows: CACF, Environmental Exposure Unit (EEU), Vienna Challenge Chamber (VCC), Fraunhofer Institute Environmental Challenge Chamber, Atlanta Allergen Exposure Unit, Biogenics Research Chamber, Allergen BioCube, Chiba and Osaka Environmental Challenge Chamber, exposure unit, challenge chamber, or environmental exposure chamber. Articles were then selected for relevance to the goals of the present review, including important contributions toward clinical and/or basic science allergy research. CACFs offer sensitive, specific, and reproducible methodology for allergen challenge. They have been employed since the 1980s and offer distinct advantages over traditional in-season multicentre trials when evaluating new treatments for AR. They have provided clinically applicable efficacy and pharmacologic information about important allergy medications, including antihistamines, decongestants, antileukotrienes, immunotherapies, and nasal steroids. CACF models have also contributed to basic science and novel/experimental therapy research. To date, no direct studies have been conducted comparing outcomes from one CACF to another. Over the past decade, CACF models have played an essential role in investigating the pathophysiology of AR and evaluating new therapies. The future opportunities for this model continue to expand. PMID:26130471

  8. Imaging Biomarkers in Immunotherapy

    PubMed Central

    Juergens, Rosalyn A.; Zukotynski, Katherine A.; Singnurkar, Amit; Snider, Denis P.; Valliant, John F.; Gulenchyn, Karen Y.

    2016-01-01

    Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer. PMID:26949344

  9. Cytokines in Cancer Immunotherapy

    PubMed Central

    Lee, Sylvia; Margolin, Kim

    2011-01-01

    Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system to eradicate cancer has been accompanied by heightened efforts to characterize cytokines and exploit their vast signaling networks to develop cancer treatments. The goal of this paper is to review the major cytokines involved in cancer immunotherapy and discuss their basic biology and clinical applications. The paper will also describe new cytokines in pre-clinical development, combinations of biological agents, novel delivery mechanisms, and potential directions for future investigation using cytokines. PMID:24213115

  10. Immunotherapy for Pediatric Leukemia

    PubMed Central

    Shah, Nirali N.; Dave, Hema; Wayne, Alan S.

    2013-01-01

    Substantial progress has been made in the treatment of leukemia in childhood. Despite this, leukemia remains a leading cause of pediatric cancer-related mortality and the prognosis is guarded for individuals with relapsed or refractory disease. Standard therapies are associated with a wide array of acute and long-term toxicities and further treatment intensification may not be tolerable or beneficial. The curative potential of allogeneic stem cell transplantation is due in part to the graft-versus-leukemia effect, which provides evidence for the therapeutic capacity of immune-based therapies. In recent years there have been significant advances in the development and application of immunotherapy in the treatment of leukemias, including the demonstration of activity in chemotherapy-resistant cases. This review summarizes immunotherapeutic approaches in the treatment of pediatric leukemia including current results and future directions. PMID:23847759

  11. Grass Pollen Allergens

    PubMed Central

    Augustin, Rosa; Hayward, Barbara J.

    1962-01-01

    Cocksfoot and Timothy pollen extracts are each found to contain at least fifteen components antigenic in rabbits. Most of these can also be allergens for man, but only a few are regularly so. These `principal' allergens have now been isolated in highly purified form. Procedures are given for a simple method of preparing extracts for clinical purposes and for the partial separation, concentration and purification of the allergens by means of differential extractions of the pollens and by means of ultrafiltration, isoelectric precipitation and salt fractionations (at acid and neutral pH) of the extracts. Isoelectric precipitations gave highly pigmented acid complexes, two of which moved as single sharp peaks at pH 7.4 in free electrophoresis, but proved to be hardly active by skin tests. Acid NaCl fractionation of the remainder resulted for Cocksfoot and Timothy in the isolation of a nearly white powder (T21.111121112 = T21B) which was weight for weight 1000–10,000 times as active as the pollen from which it had been derived. The powders have retained their activity for 7 years. By gel diffusion tests, they were found to contain two antigens (one in each preparation) which were immunologically partially related, but the Timothy preparation contained in addition the `innermost' `twin' antigens specific for Timothy that we had discovered previously in the crude extracts by gel diffusion methods. Skin reactions could be elicited in hay-fever subjects by prick tests with concentrations of 10-9–10-8 g./ml., which is equivalent to intradermal injections of 10-11–10-10 mg. and represents a 300-fold purification with respect to the concentrates of crude pollen extracts prepared by ultrafiltration and dialysis. Fractionation on DEAE-cellulose of one of the highly purified Timothy preparations (T21.11112112 = T21A) and other, crude Timothy and Cocksfoot extracts resulted in considerable and reproducible separation of the various antigens, with no indication of the

  12. Immunotherapy for bladder cancer

    PubMed Central

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

    2015-01-01

    It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  13. Immunotherapy for bladder cancer.

    PubMed

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James Sa

    2015-01-01

    It is nearly 40 years since Bacillus Calmette-Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  14. Genomic determinants of cancer immunotherapy.

    PubMed

    Miao, Diana; Van Allen, Eliezer M

    2016-08-01

    Cancer immunotherapies - including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade - yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict which patients are most likely to benefit from cancer immunotherapy. Continued work in harnessing genomic, transcriptomic, and immunological data from clinical cohorts of immunotherapy-treated patients will bring the promises of precision medicine to immuno-oncology. PMID:27254251

  15. Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3+ Regulatory T cells.

    PubMed

    Wu, Kui; Bi, Yuttian; Sun, Kun; Xia, Junbo; Wang, Yan; Wang, Changzheng

    2008-02-01

    CD4(+)CD25(+)Foxp3(+)Regulatory T cells (Tregs) play important roles in regulating allergic inflammation. To analyse if allergen-DNA-modified dendritic cells (DC) can suppress allergic responses and what roles Treg cells play in DC-based allergen-specific immunotherapy. Immature DC were transfected with retrovirus encoding Der p2 DNA, and administered to mice that sensitized and challenged with Der p2 protein. After Treg cells were depleted with anti-CD25 mAb, mice were re-challenged to observe the airway inflammation, and Treg cells in spleen CD4(+) T cells. And responses of spleen CD4(+) T cells to Der p2 were determined. Co-culture of naïve CD4(+) T cells with allergen-modified DC induced Foxp3+ Tregs. Sensitized and challenged mice developed allergic airway inflammation and Th2 responses, and decreased Foxp3(+) Tregs. Treatment with allergen-modified-DC suppressed airway inflammation and Th2 responses, and increased IL-10 and IFN-gamma production and Foxp3(+) Tregs significantly; and eliminated the responses of CD4(+) T cells to allergen. Administration of anit-CD25 mAb eliminated all the effects of modified-DC except for the increasing of IFN-gamma. Allergen-modified DC can induce immune tolerance to allergens and reverse the established Th2 responses induced by allergen, with dependence on the induction of Foxp3(+) Tregs. PMID:18201369

  16. Optomechanical system of AIT tools to perform tests and integrations of 24 IFU

    NASA Astrophysics Data System (ADS)

    Renault, Edgard; Laurent, Florence; Adjali, Louisa; Bacon, Roland M.; Boudon, Didier; Caillier, Patrick; Daguisé, Eric; Dubois, Jean-Pierre; Anwand, Heiko; Kosmalski, Johan; Loupias, Magali; Nicklas, Harald E.; Remillieux, Alban

    2010-07-01

    The second generation instrument MUSE (Multi Unit Spectroscopic Explorer) developed for the VLT (Very Large Telescope) for ESO (European Southern Observatory) is composed of 24 identical Integral Field Unit. To perform the tests and the integration in a shorter time, we have developed an opto-mechanical system of AIT Tools (Assembly- Integration-Test) referenced to an unique simulator of IFU. Each IFU sub system and its test bench (sources, image slicer, spectrograph, IFU) are checked with respect to the same opto-mechanical references. These references are also used to align all the 24 IFU onto the MUSE main structure. The system allows a better homogeneity between IFU in term of performances and a better traceability between its sub-systems. This paper presents the different AIT tools developed at CRAL to reach the specified performances for the serial phase of AIT of 24 IFU.

  17. A revisit to cockroach allergens.

    PubMed

    Sookrung, Nitat; Chaicumpa, Wanpen

    2010-01-01

    Among cockroaches (CR) that live in people's homes, two species, i.e., German CR (Blattella germanica) and American CR (Periplaneta americana) predominate in temperate and tropical areas, respectively. CR is an important source of inhalant indoor allergens that sensitize atopic subjects to (localized) type I hypersensitivity or atopy including allergic rhinitis and atopic asthma. In Thailand the predominant CR species is P. americana. CR allergens are found throughout CR infested houses; the number found in kitchens correlates with the degree of CR infestation while sensitization and reactivation of the allergic morbidity are likely to occur in the living room and bedroom. Levels of the CR allergens in homes of CR allergic Thais, measured by using locally made quantification test kits, revealed that the highest levels occur in dust samples collected from the wooden houses of urban slums and in the cool and dry season. CR allergens are proteins that may be derived from any anatomical part of the insect at any developmental stage. The allergens may be also from CR secretions, excretions, body washes or frass. The proteins may be the insect structural proteins, enzymes or hormones. They may exist as dimers/multimers and/or in different isoforms. Exposure to CR allergens in infancy leads to allergic morbidity later in life. Clinical symptoms of CR allergy are usually more severe and prolonged than those caused by other indoor allergens. The mechanisms of acute and chronic airway inflammation and airway hyper-responsiveness (AHR) have been addressed including specific IgE- and non-IgE-mediated mechanisms, i.e., role of protease-activated receptor-2 (PAR2). Participation of various allergen activated-CD4+ T cells of different sublineages, i.e., Th2, Th17, Th22, Th9, Th25, Tregs/Th3 as well as invariant NKT cells, in asthma pathogenesis have been mentioned. The diagnosis of CR allergy and the allergy intervention by CR population control are also discussed. PMID:21038777

  18. Gold Nanoparticle Mediated Cancer Immunotherapy

    PubMed Central

    Almeida, Joao Paulo Mattos; Figueroa, Elizabeth Raquel; Drezek, Rebekah Anna

    2013-01-01

    Significant progress has been made in the field of cancer immunotherapy, where the goal is to activate or modulate the body’s immune response against cancer. However, current immunotherapy approaches exhibit limitations of safety and efficacy due to systemic delivery. In this context, the use of nanotechnology for the delivery of cancer vaccines and immune adjuvants presents a number of advantages such as targeted delivery to immune cells, enhanced therapeutic effect, and reduced adverse outcomes. Recently, gold nanoparticles (AuNP) have been explored as immunotherapy carriers, creating new AuNP applications that merit a critical overview. This review highlights recent advances in the development of AuNP mediated immunotherapies that harness AuNP biodistribution, optical properties and their ability to deliver macromolecules such as peptides and oligonucleotides. It has been demonstrated that the use of AuNP carriers can improve the delivery and safety of immunotherapy agents, and that AuNP immunotherapies are well suited for synergistic combination therapy with existing cancer therapies like photothermal ablation. PMID:24103304

  19. Baked Egg and Milk Exposure as Immunotherapy in Food Allergy.

    PubMed

    Leonard, Stephanie A

    2016-04-01

    Baked milk and egg have the potential to act as a form of oral immunotherapy (OIT). Clinical studies have shown that a majority of milk- and egg-allergic children can tolerate these allergens modified in baked form, and immunologic changes reported in subjects ingesting baked milk and egg mirror those seen in food allergy OIT trials. In addition, several studies have indicated that resolution of milk and egg allergies occur sooner in populations regularly ingesting baked milk and egg. Oral food challenges remain the best method for determining tolerability of baked milk and egg since baseline characteristics and diagnostic testing have not been reliable predictors. In this review, we explore the tolerability of baked milk and egg and their potential as OIT treatment for milk and egg allergy. PMID:27002516

  20. Characterization of a mouse model of allergy to a major occupational latex glove allergen Hev b 5.

    PubMed

    Hardy, Charles L; Kenins, Linda; Drew, Alexander C; Rolland, Jennifer M; O'Hehir, Robyn E

    2003-05-15

    Allergen-specific immunotherapy is a clinically proven effective treatment for many allergic diseases, including asthma; however, it is not currently available for latex allergy because of the high risk of anaphylaxis. There is, therefore, a crucial need for an animal model of latex allergy in which to develop effective immunotherapy. Previous mouse models of latex allergy either did not characterize the allergic pulmonary immune response or used crude latex extracts, making it difficult to quantify the contribution of individual proteins and limiting their usefulness for developing specific immunotherapy. We immunized mice with recombinant Hev b 5, a defined major latex allergen, or latex glove protein extract, representing the range of occupationally encountered processed latex allergens. The immune response was compared with that seen in ovalbumin-immunized mice. Immunization with Hev b 5 or glove extract elicits hallmarks of allergic pulmonary Th2-type immune responses, comparable to those for ovalbumin, including (1) serum antigen-specific IgE, (2) an eosinophilic inflammatory infiltrate in the lung, (3) increased interleukin-5 in lung bronchoalveolar lavage fluid, and (4) mucus hypersecretion by epithelial cells in the lung airways. This mouse model will aid the development of potentially curative treatments for latex-sensitized individuals, including those with occupational asthma. PMID:12615623

  1. Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer

    PubMed Central

    2014-01-01

    Background We previously reported the clinical efficacy of adoptive immunotherapy (AIT) with dendritic cells (DCs) pulsed with mucin 1 (MUC1) peptide and cytotoxic T lymphocytes (CTLs). We also reported that gemcitabine (GEM) enhances anti-tumor immunity by suppressing regulatory T cells. Therefore, in the present study, we performed combination therapy with AIT and GEM for patients with unresectable or recurrent pancreatic cancer. Patients and methods Forty-two patients with unresectable or recurrent pancreatic cancer were treated. DCs were generated by culture with granulocyte macrophage colony-stimulating factor and interleukin-4 and then exposed to tumor necrosis factor-α. Mature DCs were transfected with MUC1-mRNA by electroporation (MUC1-DCs). MUC1-CTLs were induced by co-culture with YPK-1, a human pancreatic cancer cell line, and then with interleukin-2. Patients were treated with GEM, while MUC1-DCs were intradermally injected, and MUC1-CTLs were intravenously administered. Results Median survival time (MST) was 13.9 months, and the 1-year survival rate was 51.1%. Of 42 patients, one patient had complete response (2.4%), three patients had partial response (7.1%) and 22 patients had stable disease (52.4%). The disease control ratio was 61.9%. The MST and 1-year survival rate of 35 patients who received more than 1 × 107 MUC1-DCs per injection was 16.1 months and 60.3%, respectively. Liver metastasis occurred in only 5 patients among 35 patients without liver metastasis before treatment. There were no severe toxicities associated with AIT. Conclusion AIT with MUC1-DCs and MUC1-CTLs plus GEM may be a feasible and effective treatment for pancreatic cancer. PMID:24947606

  2. Crystal structure of peanut (Arachis hypogaea) allergen Ara h 5

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Profilins from numerous species are known to be allergens, including food allergens, such as peanut (Arachis hypogaea) allergen Ara h 5, and pollen allergens, such as birch allergen Bet v 2. Patients with pollen allergy can also cross-react to peanut. Structural characterization of allergens will al...

  3. Immunotherapy of Brain Cancer.

    PubMed

    Roth, Patrick; Preusser, Matthias; Weller, Michael

    2016-01-01

    The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti-cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors. PMID:27260656

  4. Immunotherapy for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Kosten, Thomas R.

    2013-01-01

    Substance use disorders continue to be major medical and social problems worldwide. Current medications for substance use disorders have many limitations such as cost, availability, medication compliance, dependence, diversion of some to illicit use and relapse to addiction after discontinuing their use. Immunotherapies using either passive monoclonal antibodies or active vaccines have distinctly different mechanisms and therapeutic utility from small molecule approaches to treatment. They have great potential to help the patient achieve and sustain abstinence and have fewer of the above limitations. This review covers the cocaine vaccine development in detail and provides an overview of directions for developing anti-addiction vaccines against the abuse of other substances. The notable success of the first placebo-controlled clinical trial of a cocaine vaccine, TA-CD, has led to an ongoing multi-site, Phase IIb clinical trial in 300 subjects. The results from these trials are encouarging further development of the cocaine vacine as one of the first anti-addiction vaccines to go forward to the U.S. Food and Drug Administration for review and approval for human use. PMID:22229313

  5. Immunotherapy for drug abuse.

    PubMed

    Shen, Xiaoyun; Kosten, Thomas R

    2011-12-01

    Substance use disorders continue to be major medical and social problems worldwide. Current medications for substance use disorders have many limitations such as cost, availability, medication compliance, dependence, diversion of some to illicit use and relapse to addiction after discontinuing their use. Immunotherapies using either passive monoclonal antibodies or active vaccines have distinctly different mechanisms and therapeutic utility from small molecule approaches to treatment. They have great potential to help the patient achieve and sustain abstinence and have fewer of the above limitations. This review covers the cocaine vaccine development in detail and provides an overview of directions for developing anti-addiction vaccines against the abuse of other substances. The notable success of the first placebo-controlled clinical trial of a cocaine vaccine, TA-CD, has led to an ongoing multi-site, Phase IIb clinical trial in 300 subjects. The results from these trials are encouarging further development of the cocaine vacine as one of the first anti-addiction vaccines to go forward to the U.S. Food and Drug Administration for review and approval for human use. PMID:22229313

  6. Immunotherapy in Breast Cancer.

    PubMed

    Marmé, Frederik

    2016-01-01

    The importance of the tumor microenvironment including immune cell infiltrates in breast cancer has long been recognized. Tumor-infiltrating lymphocytes are prognostic and predictive; however, their prevalence as well as their prognostic and predictive power are subtype-dependent and appear most prominent in aggressive subtypes like triple-negative and HER2-positive disease. The immune responses observed in many cancers are attracted by tumor-associated antigens and, as suggested by recent research, by neoantigens - immunogenic antigens encoded for by non-synonymous mutations. The appealing promise of cancer vaccines has been pursued in breast cancer for over 2 decades; however, despite much effort having been put into vaccine trials, their clinical benefit, with the exception of some encouraging preliminary results, remains disappointing. The main hurdles compromising the efficacy of these vaccination strategies are the difficulties to generate broad and robust immune responses as well as to overcome immune escape mechanisms. The remarkable efficacy of immune checkpoint inhibitors in melanoma and lung cancer has set the ground for a race in the clinical development of numerous agents targeting these immune escape mechanisms in many tumor entities. Early clinical data in metastatic breast cancer suggests at least some clinical activity. This review discusses the current status and future perspectives of immunotherapy in breast cancer. PMID:27260697

  7. Lymphoma Immunotherapy: Current Status

    PubMed Central

    Zappasodi, Roberta; de Braud, Filippo; Di Nicola, Massimo

    2015-01-01

    The rationale to treat lymphomas with immunotherapy comes from long-standing evidence on their distinctive immune responsiveness. Indolent B-cell non-Hodgkin lymphomas, in particular, establish key interactions with the immune microenvironment to ensure prosurvival signals and prevent antitumor immune activation. However, reports of spontaneous regressions indicate that, under certain circumstances, patients develop therapeutic antitumor immunity. Several immunotherapeutic approaches have been thus developed to boost these effects in all patients. To date, targeting CD20 on malignant B cells with the antibody rituximab has been the most clinically effective strategy. However, relapse and resistance prevent to cure approximately half of B-NHL patients, underscoring the need of more effective therapies. The recognition of B-cell receptor variable regions as B-NHL unique antigens promoted the development of specific vaccines to immunize patients against their own tumor. Despite initial promising results, this strategy has not yet demonstrated a sufficient clinical benefit to reach the regulatory approval. Several novel agents are now available to stimulate immune effector functions or counteract immunosuppressive mechanisms, such as engineered antitumor T cells, co-stimulatory receptor agonist, and immune checkpoint-blocking antibodies. Thus, multiple elements can now be exploited in more effective combinations to break the barriers for the induction of anti-lymphoma immunity. PMID:26388871

  8. Immunotherapy for malignant glioma

    PubMed Central

    Suryadevara, Carter M.; Verla, Terence; Sanchez-Perez, Luis; Reap, Elizabeth A.; Choi, Bryan D.; Fecci, Peter E.; Sampson, John H.

    2015-01-01

    Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12–15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM. PMID:25722935

  9. IgE immunotherapy

    PubMed Central

    Josephs, Debra H; Spicer, James F; Karagiannis, Panagiotis; Gould, Hannah J; Karagiannis, Sophia N

    2014-01-01

    The importance of antibodies in activating immune responses against tumors is now better appreciated with the emergence of checkpoint blockade antibodies and with engineered antibody Fc domains featuring enhanced capacity to focus potent effector cells against cancer cells. Antibodies designed with Fc regions of the IgE class can confer natural, potent, long-lived immune surveillance in tissues through tenacious engagement of high-affinity cognate Fc receptors on distinct, often tumor-resident immune effector cells, and through ability to activate these cells under tumor-induced Th2-biased conditions. Here, we review the properties that make IgE a contributor to the allergic response and a critical player in the protection against parasites, which also support IgE as a novel anti-cancer modality. We discuss IgE-based active and passive immunotherapeutic approaches in disparate in vitro and in vivo model systems, collectively suggesting the potential of IgE immunotherapies in oncology. Translation toward clinical application is now in progress. PMID:24423620

  10. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

    PubMed Central

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-01-01

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness. PMID:26862501

  11. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence.

    PubMed

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-02-01

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness. PMID:26862501

  12. Ant allergens and hypersensitivity reactions in response to ant stings.

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

    Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments. PMID:26708389

  13. Mucosal immunization application to allergic disease: sublingual immunotherapy.

    PubMed

    Frati, Franco; Moingeon, Philippe; Marcucci, Francesco; Puccinelli, Paola; Sensi, Laura; Di Cara, Giuseppe; Incorvaia, Cristoforo

    2007-01-01

    Sublingual immunotherapy (SLIT) is an effective and safe treatment for respiratory allergy, and its mechanism of action currently is investigated with increasing attention. Studies of pharmacokinetics showed that allergen extracts administered via the sublingual route are not directly absorbed by the oral mucosa but are long retained at mucosal level, where the allergen molecules are captured by dendritic cells and, following their migration in the draining lymph nodes, presented to T cells. This seems to be the pivotal factor underlying the mechanisms of action of SLIT, at least for the long-term effects, and for the short-term efficacy, observed with ultrarush or coseasonal treatment, a down-regulation of mast cells resulting in hyporeactivity at the peak of the pollen season may be suggested. Regarding the clinically established long-lasting effects, the core mechanism is likely to consist of T regulatory (Treg) cell activation. In particular, Treg cells differentiate from naive T cells after application of soluble antigens to the mucosae, a crucial factor being the tolerogenic function of dendritic cells, and exert a suppressive effect on both Th1 and Th2 responses. Moreover, at least for the type 1 cells (Treg1), a production of IL-10 with consequent down-modulation of the immune response has been reported. Another characteristic of sublingual immunization is the absence of effectors cells, viz., mast cells, basophils, and eosinophils, in the oral mucosa of allergic subjects, which account for the excellent tolerability of SLIT. PMID:17390755

  14. Clinical Efficacy and Immune Regulation With Peanut Oral Immunotherapy

    PubMed Central

    Jones, Stacie M.; Pons, Laurent; Roberts, Joseph L.; Scurlock, Amy M.; Perry, Tamara T.; Kulis, Mike; Shreffler, Wayne G.; Steele, Pamela; Henry, Karen A.; Adair, Margaret; Francis, James M.; Durham, Stephen; Vickery, Brian P.; Zhong, Xiaoping; Burks, A. Wesley

    2009-01-01

    Background Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Peanut-allergic children underwent an OIT protocol including initial day escalation, build-up, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12–18 months, while IgG4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over 6–12 months. Peanut-specific FoxP3 T cells increased until 12 months and then decreased thereafter. Additionally, T cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion OIT induces clinical desensitization to peanut, with significant longer term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT. PMID:19577283

  15. Understanding allergic asthma from allergen inhalation tests.

    PubMed

    Cockcroft, Donald W; Hargreave, Fredrick E; O'Byrne, Paul M; Boulet, Louis-Philippe

    2007-10-01

    The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors' involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic) airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta(2)-agonist-induced increase in airway response to allergen (including eosinophilic inflammation), advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a multicentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma. PMID:17948142

  16. Household Arthropod Allergens in Korea

    PubMed Central

    Jeong, Kyoung Yong

    2009-01-01

    Arthropods are important in human health, which can transmit pathogens to humans, parasitize, or produce important allergens. Allergy prevalence becomes higher in Korea recently as well as other developed countries in contrast to a decrease of infectious diseases. Allergic diseases caused by household arthropods have increased dramatically during the last few decades since human beings spend more their time for indoor activities in modernized life style. Household arthropods are one of the most common causes of allergic diseases. Biological characterization of household arthropods and researches on their allergens will provide better understanding of the pathogenesis of allergic diseases and suggest new therapeutic ways. Therefore, studies on arthropods of allergenic importance can be considered one of the major research areas in medical arthropodology and parasitology. Here, the biology of several household arthropods, including house dust mites and cockroaches, the 2 most well known arthropods living indoor together with humans worldwide, and characteristics of their allergens, especially the research activities on these allergens performed in Korea, are summarized. PMID:19885330

  17. Does pollen "neighborhood" affect yield in lowbush blueberry (Vaccinium angustifolium Ait.)?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proximally growing individuals of wild, lowbush blueberry (Vaccinium angustifolium Ait.) vary widely in yield despite being grown under conditions in which environmental heterogeneity is minimized by cultivation practices. We recently established that the relative self-fertility of the bearing plan...

  18. Preliminary analysis of genetic diversity in lowbush blueberry (Vaccinium angustifolium Ait.) across its native range

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lowbush blueberry (Vaccinium angustifolium Ait.) is unique in its cultivation. Wild plants colonize open areas, either natural or man-made. Without planted varieties it is left to chance and selection what genotypes will populate a field. Population screening of clones in blueberry fields and surrou...

  19. Mining and validation of pyrosequenced simple sequence repeats (SSRs) from American cranberry (Vaccinium macrocarpon Ait.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The American cranberry (Vaccinium macrocarpon Ait.) is a major commercial fruit crop in North America, but limited genetic resources have been developed for the species. Furthermore, the paucity of DNA markers has hampered the advance of genetic research in cranberry and the Ericaceae family in gene...

  20. The spatial genetic structure of lowbush blueberry, Vaccinium angustifolium Ait., in four fields in Maine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Expressed Sequence Tag-Polymerase Chain Reaction (EST-PCR) molecular markers were used to infer spatial genetic structure (SGS) of four lowbush blueberry (Vaccinium angustifolium Ait.) fields in Maine. Genetic structure was quantified at three spatial scales: 1) within apparent clones (or intrapat...

  1. Acquired resistance to immunotherapy and future challenges.

    PubMed

    Restifo, Nicholas P; Smyth, Mark J; Snyder, Alexandra

    2016-02-01

    Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy. PMID:26822578

  2. Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis.

    PubMed

    Lourenço, Edmir Américo; Caldeira, Eduardo José; Carvalho, César Alexandre Fabrega; Cunha, Marcelo Rodriques; Carvalho, Marcus Vinícius Henriques; Passos, Saulo Duarte

    2016-01-01

    Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions. PMID:26722338

  3. Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis

    PubMed Central

    Lourenço, Edmir Américo; Caldeira, Eduardo José; Carvalho, César Alexandre Fabrega; Cunha, Marcelo Rodriques; Carvalho, Marcus Vinícius Henriques; Passos, Saulo Duarte

    2015-01-01

    Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions. PMID:26722338

  4. [Specific immunotherapy and relocation in occupational allergic bakers].

    PubMed

    Cirla, A M; Lorenzini, R A; Cirla, P E

    2007-01-01

    Occupational allergy to components of wheat flour is the main cause of rhinitis and asthma of workers in bakeries and similar activities. An immunological mechanism IgE-mediated is involved and the sensitising properties of some proteins of wheat where assessed. Nowadays it is possible to have an extract to be used for specific immunotherapy. The aim of this treatment should be a reduction of individual immunological reactivity and the possibility of going on the particular activity of allergic bakers, pastry makers or pizza makers. An observational crossectional retrospective study was performed on 41 sensitised workers that were diagnosed in the same occupational health unit. All underwent a subcutaneous specific immunotherapy (SCIT) with the same schedule and the same extract (Lofarma Allergeni, Milan) for 4 or more years, without avoiding their work activity. The outcome was investigated after five or ten years. Data were collected by a questionnaire. 34 subjects on 41 are still at work with an acceptable quality of life and a normal working efficiency, mainly in their small enterprises. In the "old" subgroup (19 cases), treated in the past, several bakers still at work stopped SCIT even from 4-10 years. In the "new" subgroup (15 cases), still in treatment, symptoms and drug use during the work activity resulted to be reduced or absent in the majority of cases. According to results of other immunotherapies by allergenic vaccines (pollens, mites) also for wheat flour occupational allergy a specific treatment seems to be possible and SCIT may be an useful tool to reduce and control the biological individual effects of allergy. By the occupational point of view wheat flour SCIT allows a relocation in many of cases and may be associated to other intervention of environmental prevention at workplaces, improving the relocation of occupational allergic subjects when requested. PMID:18409768

  5. Immunotherapy for tuberculosis: future prospects

    PubMed Central

    Abate, Getahun; Hoft, Daniel F

    2016-01-01

    Tuberculosis (TB) is still a major global health problem. A third of the world’s population is infected with Mycobacterium tuberculosis. Only ~10% of infected individuals develop TB but there are 9 million TB cases with 1.5 million deaths annually. The standard prophylactic treatment regimens for latent TB infection take 3–9 months, and new cases of TB require at least 6 months of treatment with multiple drugs. The management of latent TB infection and TB has become more challenging because of the spread of multidrug-resistant and extremely drug-resistant TB. Intensified efforts to find new TB drugs and immunotherapies are needed. Immunotherapies could modulate the immune system in patients with latent TB infection or active disease, enabling better control of M. tuberculosis replication. This review describes several types of potential immunotherapies with a focus on those which have been tested in humans. PMID:27529060

  6. Immunotherapy of Childhood Sarcomas.

    PubMed

    Roberts, Stephen S; Chou, Alexander J; Cheung, Nai-Kong V

    2015-01-01

    Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing's family of tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with localized stage are curable with surgery and/or chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New therapies for these patients are urgently needed. Immunotherapy is an established treatment modality for both liquid and solid tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In the past, immunomodulatory agents such as interferon, interleukin-2, and liposomal-muramyl tripeptide phosphatidyl-ethanolamine have been tried, with some activity seen in subsets of patients; additionally, various cancer vaccines have been studied with possible benefit. Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA-4 and PD-1 are being actively explored in pediatric sarcomas. Building on the success of adoptive T cell therapy for EBV-related lymphoma, strategies to redirect T cells using chimeric antigen receptors and bispecific antibodies are rapidly evolving with potential for the treatment of sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and tumor vaccines. The future integration of antibody-based and cell-based therapies into an overall treatment strategy of sarcoma will be discussed. PMID:26301204

  7. Immunotherapy of Childhood Sarcomas

    PubMed Central

    Roberts, Stephen S.; Chou, Alexander J.; Cheung, Nai-Kong V.

    2015-01-01

    Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing’s family of tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with localized stage are curable with surgery and/or chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New therapies for these patients are urgently needed. Immunotherapy is an established treatment modality for both liquid and solid tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In the past, immunomodulatory agents such as interferon, interleukin-2, and liposomal-muramyl tripeptide phosphatidyl-ethanolamine have been tried, with some activity seen in subsets of patients; additionally, various cancer vaccines have been studied with possible benefit. Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA-4 and PD-1 are being actively explored in pediatric sarcomas. Building on the success of adoptive T cell therapy for EBV-related lymphoma, strategies to redirect T cells using chimeric antigen receptors and bispecific antibodies are rapidly evolving with potential for the treatment of sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and tumor vaccines. The future integration of antibody-based and cell-based therapies into an overall treatment strategy of sarcoma will be discussed. PMID:26301204

  8. Cow’s milk allergy: From allergens to new forms of diagnosis, therapy and prevention☆

    PubMed Central

    Hochwallner, Heidrun; Schulmeister, Ulrike; Swoboda, Ines; Spitzauer, Susanne; Valenta, Rudolf

    2014-01-01

    The first adverse reactions to cow’s milk were already described 2000 years ago. However, it was only 50 years ago that several groups started with the analysis of cow’s milk allergens. Meanwhile the spectrum of allergy eliciting proteins within cow’s milk is identified and several cow’s milk allergens have been characterized regarding their biochemical properties, fold and IgE binding epitopes. The diagnosis of cow’s milk allergy is diverse ranging from fast and cheap in vitro assays to elaborate in vivo assays. Considerable effort was spent to improve the diagnosis from an extract-based into a component resolved concept. There is still no suitable therapy available against cow’s milk allergy except avoidance. Therefore research needs to focus on the development of suitable and safe immunotherapies that do not elicit severe side effect. PMID:23954566

  9. [The NTP in allergy research : open questions regarding nasal provocation tests using allergens].

    PubMed

    Förster, U; Sperl, A; Klimek, L

    2013-10-01

    The nasal provocation test (NPT) is a simple procedure with high specificity and sensitivity that is used in the investigation of allergic and nonallergic diseases. Uniform standards are of particular importance in the clinical setting and for the comparability of clinical and basic allergy research. These standards should cover the composition, dosage and pharmacological formulation of provocative substances (e.g. allergen extracts), the necessity of titration, allergen application methods and the evaluation criteria for a positive NPT reaction. Detection of various mediators and cytokines in nasal discharge can be very useful in the late phase reactions. NPT finds specific applications in studies of local IgE secretion in the nasal mucosa, the diagnosis of analgesic intolerance and in assessments of the efficacy of specific immunotherapies. Additional parameters warranting further evaluation include provocation with cold dry air in nasal hyperreactivity patients and nasal nitric oxide formation. Determination of nasal blood flow during NPT provides an additional clinical parameter. PMID:24127046

  10. Cow's milk allergy: from allergens to new forms of diagnosis, therapy and prevention.

    PubMed

    Hochwallner, Heidrun; Schulmeister, Ulrike; Swoboda, Ines; Spitzauer, Susanne; Valenta, Rudolf

    2014-03-01

    The first adverse reactions to cow's milk were already described 2,000 years ago. However, it was only 50 years ago that several groups started with the analysis of cow's milk allergens. Meanwhile the spectrum of allergy eliciting proteins within cow's milk is identified and several cow's milk allergens have been characterized regarding their biochemical properties, fold and IgE binding epitopes. The diagnosis of cow's milk allergy is diverse ranging from fast and cheap in vitro assays to elaborate in vivo assays. Considerable effort was spent to improve the diagnosis from an extract-based into a component resolved concept. There is still no suitable therapy available against cow's milk allergy except avoidance. Therefore research needs to focus on the development of suitable and safe immunotherapies that do not elicit severe side effect. PMID:23954566

  11. Removing peanut allergens by tannic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tannic acid (TA) is known to bind and form insoluble complexes with proteins, including peanut allergens; however, whether such complexes would dissociate and release the allergens at pH 2 and 8 (i.e., gastric and intestinal pH) is not clear. Release of the allergens in the gut could lead to absorpt...

  12. Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.

    PubMed

    Tyagi, Nidhi; Farnell, Edward J; Fitzsimmons, Colin M; Ryan, Stephanie; Tukahebwa, Edridah; Maizels, Rick M; Dunne, David W; Thornton, Janet M; Furnham, Nicholas

    2015-10-01

    Allergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods) in mammalian hosts. Based on the hypothesis that IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause allergy, we predict that the environmental allergens will share key properties with the metazoan parasite antigens that are specifically targeted by IgE in infected human populations. We seek to test this prediction by examining if significant similarity exists between molecular features of allergens and helminth proteins that induce an IgE response in the human host. By employing various computational approaches, 2712 unique protein molecules that are known IgE antigens were searched against a dataset of proteins from helminths and parasitic arthropods, resulting in a comprehensive list of 2445 parasite proteins that show significant similarity through sequence and structure with allergenic proteins. Nearly half of these parasite proteins from 31 species fall within the 10 most abundant allergenic protein domain families (EF-hand, Tropomyosin, CAP, Profilin, Lipocalin, Trypsin-like serine protease, Cupin, BetV1, Expansin and Prolamin). We identified epitopic-like regions in 206 parasite proteins and present the first example of a plant protein (BetV1) that is the commonest allergen in pollen in a worm, and confirming it as the target of IgE in schistosomiasis infected humans. The identification of significant similarity, inclusive of the epitopic regions, between allergens and helminth proteins against which IgE is an observed marker of protective immunity explains the 'off-target' effects of the IgE-mediated immune system in allergy. All these findings can impact the discovery and design of molecules

  13. Effect of chemical modifications on allergenic potency of peanut proteins

    PubMed Central

    Bencharitiwong, Ramon; van der Kleij, Hanneke P.M.; Koppelman, Stef J.

    2015-01-01

    Background: Modification of native peanut extracts could reduce adverse effects of peanut immunotherapy. Objective: We sought to compare native and chemically modified crude peanut extract (CPE) and major peanut allergens Ara h 2 and Ara h 6 in a mediator-release assay based on the rat basophilic leukemia (RBL) cell line transfected with human Fcε receptor. Methods: Native Ara h 2/6 was reduced and alkylated (RA), with or without additional glutaraldehyde treatment (RAGA). CPE was reduced and alkylated. Sera of subjects with peanut allergy (16 males; median age 7 years) were used for overnight RBL-passive sensitization. Cells were stimulated with 0.1 pg/mL to 10 μg/mL of peanut. β-N-acetylhexosaminidase release (NHR) was used as a marker of RBL degranulation, expressed as a percentage of total degranulation caused by Triton X. Results: Median peanut-specific immunoglobulin E was 233 kUA/L. Nineteen subjects were responders, NHR ≥ 10% in the mediator release assay. Responders had reduced NHR by RA and RAGA compared with the native Ara h 2/6. Modification resulted in a later onset of activation by 10- to 100-fold in concentration and a lowering of the maximum release. Modified RA-Ara h 2/6 and RAGA-Ara h 2/6 caused significantly lower maximum mediator release than native Ara h 2/6, at protein concentrations 0.1, 1, and 10 ng/mL (p < 0.001, < 0.001, and < 0.001, respectively, for RA; and < 0.001, 0.026, and 0.041, respectively, for RAGA). RA-CPE caused significantly lower maximum NHR than native CPE, at protein concentration 1 ng/mL (p < 0.001) and 10 ng/mL (p < 0.002). Responders had high rAra h 2 immunoglobulin E (mean, 61.1 kUA/L; p < 0.001) and higher NHR in mediator release assay to native Ara h 2/6 than CPE, which indicates that Ara h 2/6 were the most relevant peanut allergens in these responders. Conclusions: Chemical modification of purified native Ara h 2 and Ara h 6 reduced mediator release in an in vitro assay ∼100-fold, which indicates decreased

  14. Allergenic potential of novel foods.

    PubMed

    Meredith, Clive

    2005-11-01

    Concerns have been expressed that the introduction of novel foods into the diet might lead to the development of new food allergies in consumers. Novel foods can be conveniently divided into GM and non-GM categories. Decision-tree approaches (e.g. International Life Sciences Institute-International Food Biotechnology Council and WHO/FAO) to assess the allergenic potential of GM foods were developed following the discovery, during product development, of the allergenic potential of GM soyabean expressing a gene encoding a storage protein from Brazil nut (Bertolletia excelsa). Within these decision trees considerations include: the source of the transgene; amino acid homology with known allergens; cross-reactivity with IgE from food-allergic individuals; resistance to proteolysis; prediction using animal models of food allergy. Such decision trees are under constant review as new knowledge and improved models emerge, but they provide a useful framework for the assessment of the allergenic potential of GM foods. For novel non-GM foods the assessment of allergenic potential is more subjective; some foods or food ingredients will need no assessment other than a robust protein assay to demonstrate the absence of protein. Where protein is present in the novel non-GM food, hazard and risk assessments need to be made in terms of the quantity of protein that might be consumed, the identity of individual protein components and their relationships to known food allergens. Where necessary, this assessment would extend to serum screening for potential cross-reactivities, skin-prick tests in previously-sensitised individuals and double-blind placebo-controlled food challenges. PMID:16313692

  15. Fish Allergens at a Glance: Variable Allergenicity of Parvalbumins, the Major Fish Allergens

    PubMed Central

    Kuehn, Annette; Swoboda, Ines; Arumugam, Karthik; Hilger, Christiane; Hentges, François

    2014-01-01

    Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand, some individuals have IgE antibodies directed against unique, species-specific parvalbumin epitopes, and these patients show clinical symptoms only with certain fish species. Furthermore, different parvalbumin isoforms and isoallergens are present in the same fish and might display variable allergenicity. This was shown for salmon homologs, where only a single parvalbumin (beta-1) isoform was identified as allergen in specific patients. In addition to the parvalbumins, several other fish proteins, enolases, aldolases, and fish gelatin, seem to be important allergens. New clinical and molecular insights advanced the knowledge and understanding of fish allergy in the last years. These findings were useful for the advancement of the IgE-based diagnosis and also for the management of fish allergies consisting of advice and treatment of fish-allergic patients. PMID:24795722

  16. Cancer testis antigen and immunotherapy

    PubMed Central

    Krishnadas, Deepa Kolaseri; Bai, Fanqi; Lucas, Kenneth G

    2013-01-01

    The identification of cancer testis (CT) antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1), melanoma antigen family A, 3 (MAGE-A3), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) in various malignancies, and presents our current understanding of CT antigen based immunotherapy.

  17. Expression of yellow jacket and wasp venom Ag5 allergens in bacteria and in yeast.

    PubMed

    Monsalve, R I; Lu, G; King, T P

    1999-01-01

    Antigen 5 (Ag5), of unknown biological function, is one of the major venom allergens of vespids and fire ants. We have compared the expression of Ag5 in bacteria and in yeast. Recombinant Ag5 from bacteria formed an insoluble intracellular product, which was not properly folded, but that produced in Pichia pastoris was secreted to the extracellular medium. Immunochemical characterizations showed the secreted Ag5 to have the native structure of the natural protein. This is of interest since the B cell epitopes of Ag5 are mainly of the discontinuous type. These studies were made with Ag5s from yellow jacket (Vespula vulgaris) and paper wasp (Polistes annularis), and with hybrid Ag5 molecules that contained partial sequences of these two species. In vitro allergenicity studies with sera from yellow jacket-sensitive patients showed that some of these hybrid molecules had a greatly reduced allergenicity but retained the immunogenicity of the natural allergen. This could be of importance for immunotherapy of this type of allergy. PMID:11487873

  18. A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A.

    PubMed

    Jonsdottir, Sigridur; Svansson, Vilhjalmur; Stefansdottir, Sara Bjork; Schüpbach, Gertraud; Rhyner, Claudio; Marti, Eliane; Torsteinsdottir, Sigurbjorg

    2016-04-01

    Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA. Injection with allergens in both Alum and Alum/MPLA resulted in significant increase in specific IgG subclasses and IgA against all r-allergens with no significant differences between the adjuvant groups. The induced antibodies from both groups could block binding of allergen specific IgE from IBH affected horses to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated PBMC from Alum/MPLA horses but not from Alum only horses produced significantly more IFNγ and IL-10 than PBMC from non-vaccinated control horses. In conclusion, intralymphatic administration of small amounts of pure allergens in Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a promising approach for immunoprophylaxis and immunotherapy against IBH. PMID:27032498

  19. Identification of Der p 23, a Peritrophin-like Protein, as a New Major Dermatophagoides pteronyssinus Allergen Associated with the Peritrophic Matrix of Mite Fecal Pellets

    PubMed Central

    Weghofer, Margit; Grote, Monika; Resch, Yvonne; Casset, Anne; Kneidinger, Michael; Kopec, Jolanta; Thomas, Wayne R.; Fernández-Caldas, Enrique; Kabesch, Michael; Ferrara, Rosetta; Mari, Adriano; Purohit, Ashok; Pauli, Gabrielle; Horak, Friedrich; Keller, Walter; Valent, Peter; Valenta, Rudolf; Vrtala, Susanne

    2015-01-01

    The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy. PMID:23460742

  20. Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets.

    PubMed

    Weghofer, Margit; Grote, Monika; Resch, Yvonne; Casset, Anne; Kneidinger, Michael; Kopec, Jolanta; Thomas, Wayne R; Fernández-Caldas, Enrique; Kabesch, Michael; Ferrara, Rosetta; Mari, Adriano; Purohit, Ashok; Pauli, Gabrielle; Horak, Friedrich; Keller, Walter; Valent, Peter; Valenta, Rudolf; Vrtala, Susanne

    2013-04-01

    The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy. PMID:23460742

  1. Emergent and unusual allergens in cosmetics.

    PubMed

    Pascoe, David; Moreau, Linda; Sasseville, Denis

    2010-01-01

    Allergic contact dermatitis from cosmetics is a common problem that is occasionally caused by new or rare allergens. When a patient has a positive patch test to a cosmetic product but to none of the common or commercially available allergens, it is important to further patch-test this patient to the ingredients of the product. Thorough testing with the breakdown of ingredients, usually obtained through cooperation with the manufacturer, often allows identification of the culprit allergen in the cosmetic product. In this article, we discuss emerging or rare allergens discovered by this method, including nail lacquer and lipstick allergens, copolymers, shellac, alkyl glucosides, glycols, protein derivatives, idebenone, and octocrylene. PMID:20487655

  2. Dermatophagoides farinae Allergens Diversity Identification by Proteomics*

    PubMed Central

    An, Su; Chen, Lingling; Long, Chengbo; Liu, Xiaoyu; Xu, Xuemei; Lu, Xingre; Rong, Mingqiang; Liu, Zhigang; Lai, Ren

    2013-01-01

    The most important indoor allergens for humans are house dust mites (HDM). Fourteen Dermatophagoides farinae allergens (Der f 1–3, 6, 7, 10, 11, 13–18, and 22) are reported although more than 30 allergens have been estimated in D. farinae. Seventeen allergens belonging to 12 different groups were identified by a procedure of proteomics combined with two-dimensional immunoblotting from D. farina extracts. Their sequences were determined by Edman degradation, mass spectrometry analysis, and cDNA cloning. Their allergenicities were assayed by enzyme-linked immunosorbent assay inhibition tests, immunoblots, basophil activation test, and skin prick tests. Eight of them are the first report as D. farinae allergens. The procedure of using a proteomic approach combined with a purely discovery approach using sera of patients with broad IgE reactivity profiles to mite allergens was an effective method to investigate a more complete repertoire of D. farinae allergens. The identification of eight new D. farinae allergens will be helpful for HDM allergy diagnosis and therapy, especially for patients without response for HDM major allergens. In addition, the current work significantly extendedthe repertoire of D. farinae allergens. PMID:23481662

  3. Allergens causing atopic diseases in canine.

    PubMed

    Youn, Hwa-Young; Kang, Hyung-Seok; Bhang, Dong-Ha; Kim, Min-Kue; Hwang, Cheol-Yong; Han, Hong-Ryul

    2002-12-01

    Canine atopic skin disease is seasonal or sometimes non-seasonal immune-mediated skin disease which occurs commonly in Korea. The definite clinical sign is systemic pruritus, especially on periocular parts, external ear, interdigit spaces and lateral flank. For diagnosis of this dermatitis, complete history taking followed by intradermal skin test and serum in vitro IgE test needs to be performed. Allergen selection for the diagnosis and treatment of atopic dermatitis should be varied geographically. In this study, with intradermal skin test(IDST) the prevalence of atopic disease and what allergens are involved in are researched. Allergens used for IDST included 26 allergen extracts from six allergen groups: grasses, trees, weeds, molds, epidermal allergens and environmental allergens. The number of allergens was 42 in which the positive and negative controls are included. The most common positive allergen reaction was the house dust mites on IDST(22/35, 63%). The other positive allergen reactions were to flea(3/35, 9%), molds(1/35, 3%), house dusts(2/35, 6%), feathers (1/35, 3%), cedar/juniper(1/35, 3%), timothy grass(1/35, 3%) and dandelion(1/35, 3%). In this study, the most prevalent allergen causing atopic dermatitis in dogs in Korea was the house dust mites followed by the flea. PMID:12819384

  4. Classification of current anticancer immunotherapies.

    PubMed

    Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, José-Manuel; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P; Coussens, Lisa; Dhodapkar, Madhav V; Eggermont, Alexander M; Fearon, Douglas T; Fridman, Wolf H; Fučíková, Jitka; Gabrilovich, Dmitry I; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M; Klein, Eva; Knuth, Alexander; Lewis, Claire E; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J; Mittendorf, Elizabeth A; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E; Pienta, Kenneth J; Porgador, Angel; Prendergast, George C; Rabinovich, Gabriel A; Restifo, Nicholas P; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J; Speiser, Daniel E; Spisek, Radek; Srivastava, Pramod K; Talmadge, James E; Tartour, Eric; Van Der Burg, Sjoerd H; Van Den Eynde, Benoît J; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S; Whiteside, Theresa L; Wolchok, Jedd D; Zitvogel, Laurence; Zou, Weiping; Kroemer, Guido

    2014-12-30

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  5. Immunotherapy Approaches in Cancer Treatment.

    PubMed

    Klener, Pavel; Otáhal, Pavel; Lateckova, Lucie; Klener, Pavel

    2015-01-01

    Tumor immune surveillance paradigm presumes that most pre-malignant cells or early malignant lesions can be eliminated (or at least controlled) by cells of the immune system. A critical feature that distinguishes advanced tumors from early neoplastic lesions is their capability to evade immune control. As a consequence, vast majority of clinically evident (advanced) tumors are poorly immunogenic. The principle goal of immunotherapy is thus a resurrection of the patient's inefficient or suppressed immune system so that it would once again become capable of launching sustained cytolytic attacks against tumor cells, which would ideally result in total and permanent eradication of cancer. Such activation of patient's anticancer immunity, however, can be achieved by strikingly different ways. This current review discusses diverse innovative immunotherapy approaches, which in the last 20 years achieved miraculous successes in the ever-lasting battle against cancer, including cytokine-based immunotherapy approaches, therapeutic monoclonal antibodies and their derivatives, cancer vaccines, and cell-based immunotherapy approaches. PMID:26087990

  6. Engineering opportunities in cancer immunotherapy

    PubMed Central

    Jeanbart, Laura; Swartz, Melody A.

    2015-01-01

    Immunotherapy has great potential to treat cancer and prevent future relapse by activating the immune system to recognize and kill cancer cells. A variety of strategies are continuing to evolve in the laboratory and in the clinic, including therapeutic noncellular (vector-based or subunit) cancer vaccines, dendritic cell vaccines, engineered T cells, and immune checkpoint blockade. Despite their promise, much more research is needed to understand how and why certain cancers fail to respond to immunotherapy and to predict which therapeutic strategies, or combinations thereof, are most appropriate for each patient. Underlying these challenges are technological needs, including methods to rapidly and thoroughly characterize the immune microenvironment of tumors, predictive tools to screen potential therapies in patient-specific ways, and sensitive, information-rich assays that allow patient monitoring of immune responses, tumor regression, and tumor dissemination during and after therapy. The newly emerging field of immunoengineering is addressing some of these challenges, and there is ample opportunity for engineers to contribute their approaches and tools to further facilitate the clinical translation of immunotherapy. Here we highlight recent technological advances in the diagnosis, therapy, and monitoring of cancer in the context of immunotherapy, as well as ongoing challenges. PMID:26598681

  7. Immunotherapy toxic in obese mice.

    PubMed

    2015-01-01

    New research shows immunotherapy can cause lethal inflammation in both young and aged mice that are obese. Restricting calories in aged mice protected them from toxicity, and giving young obese mice a drug for autoimmune disease prevented the fatal reactions. PMID:25583780

  8. Classification of current anticancer immunotherapies

    PubMed Central

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  9. Future perspectives in cancer immunotherapy

    PubMed Central

    Mountzios, Giannis; Curigliano, Giuseppe

    2016-01-01

    The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors. In particular, immune check-point inhibition in melanoma, non-small-cell lung cancer and renal cancer, peptide vaccination in prostate cancer and glioblastoma, and oncolytic immunotherapy in melanoma are well-established therapeutic modalities that have obtained approval by regulatory authorities and are already in clinical use. A large number of ongoing clinical trials involving thousands of patients are currently seeking to define the appropriate tumor type, therapeutic setting, treatment combination and patient populations in order to maximize clinical benefit from immunotherapeutic agents. In this context, identification of the patients whose tumors are most likely to respond to immunotherapy by the use of appropriate biomarkers will be crucial for the optimal implementation of immunotherapy into the therapeutic armamentarium. PMID:27563660

  10. Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens.

    PubMed

    Werfel, T; Asero, R; Ballmer-Weber, B K; Beyer, K; Enrique, E; Knulst, A C; Mari, A; Muraro, A; Ollert, M; Poulsen, L K; Vieths, S; Worm, M; Hoffmann-Sommergruber, K

    2015-09-01

    In older children, adolescents, and adults, a substantial part of all IgE-mediated food allergies is caused by cross-reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross-reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild, or severe systemic reactions may occur already after the first consumption of a food containing a cross-reactive allergen. In clinical practice, clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component-resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen-related food allergy is not clear, and more placebo-controlled studies are needed. As we are facing an increasing incidence of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, and the occurrence of new, so far unknown allergies due to cross-reactions are expected. PMID:26095197

  11. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children

    PubMed Central

    Thyagarajan, Ananth; Jones, Stacie M.; Calatroni, Agustin; Pons, Laurent; Kulis, Mike; Woo, Caitlin S.; Kamalakannan, Mohanapriya; Vickery, Brian P.; Scurlock, Amy M.; Burks, A. Wesley; Shreffler, Wayne G.

    2013-01-01

    Background In Westernized countries, over 1% of the population is allergic to peanuts or tree nuts, which carries a risk of severe allergic reactions. Several studies support the efficacy of peanut oral immunotherapy (OIT) for reducing the clinical sensitivity of affected individuals; however, the mechanisms of this effect are still being characterized. One mechanism that may contribute is the suppression of effector cells, such as basophils. Basophil anergy has been characterized in vitro as a pathway-specific hyporesponsiveness; however, this has not been demonstrated to occur in vivo. Objective To evaluate the hypothesis that basophil anergy occurs in vivo due to chronic allergen exposure in the setting of a clinical oral immunotherapy trial. Methods Samples of peripheral blood were obtained from subjects during a placebo-controlled clinical trial of peanut OIT. Basophil reactivity to in vitro stimulation with peanut allergen and controls was assessed by the upregulation of activation markers, CD63 and CD203c, measured by flow cytometry. Results The upregulation of CD63 following stimulation of the IgE receptor, either specifically with peanut allergen or non-specifically with anti-IgE antibody, was strongly suppressed by active OIT. However, OIT did not significantly suppress this response in basophils stimulated by the distinct fMLP receptor pathway. In the subset of subjects with egg sensitization, active peanut OIT also suppressed CD63 upregulation in response to stimulation with egg allergen. Allergen OIT also suppressed the upregulation of CD203c including in response to stimulation with IL-3 alone. Conclusion Peanut OIT induces a hyporesponsive state in basophils that is consistent with pathway-specific anergy previously described in vitro. This suggests the hypothesis that effector cell anergy could contribute to clinical desensitization. PMID:22805467

  12. Production of recombinant allergens in plants

    PubMed Central

    2010-01-01

    A large percentage of allergenic proteins are of plant origin. Hence, plant-based expression systems are considered ideal for the recombinant production of certain allergens. First attempts to establish production of plant-derived allergens in plants focused on transient expression in Nicotiana benthamiana infected with recombinant viral vectors. Accordingly, allergens from birch and mugwort pollen, as well as from apple have been expressed in plants. Production of house dust mite allergens has been achieved by Agrobacterium-mediated transformation of tobacco plants. Beside the use of plants as production systems, other approaches have focused on the development of edible vaccines expressing allergens or epitopes thereof, which bypasses the need of allergen purification. The potential of this approach has been convincingly demonstrated for transgenic rice seeds expressing seven dominant human T cell epitopes derived from Japanese cedar pollen allergens. Parallel to efforts in developing recombinant-based diagnostic and therapeutic reagents, different gene-silencing approaches have been used to decrease the expression of allergenic proteins in allergen sources. In this way hypoallergenic ryegrass, soybean, rice, apple, and tomato were developed. PMID:21258627

  13. Food Allergens: Is There a Correlation between Stability to Digestion and Allergenicity?

    PubMed

    Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard

    2016-07-01

    Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. It has not yet been established what makes a dietary protein a food allergen. Several characteristics have been proposed to be shared by food allergens. One of these is resistance to digestion. This paper reviews data from digestibility studies on purified food allergens and evaluates the predictive value of digestibility tests on the allergenic potential. We point out that food allergens do not necessarily resist digestion. We discuss how the choice of in vitro digestibility assay condition and the method used for detection of residual intact protein as well as fragments hereof may greatly influence the outcome as well as the interpretation of results. The finding that digests from food allergens may retain allergenicity, stresses the importance of using immunological assays for evaluating the allergenic potential of food allergen digestion products. Studies assessing the allergenicity of digestion products, by either IgE-binding, elicitation or sensitizing capacity, shows that digestion may abolish, decrease, have no effect, or even increase the allergenicity of food allergens. Therefore, the predictive value of the pepsin resistance test for assessing the allergenic potential of novel proteins can be questioned. PMID:25607526

  14. [Cancer immunotherapy by immuno-checkpoint blockade].

    PubMed

    Kawakami, Yutaka

    2015-10-01

    As cancer immunotherapies utilizing anti-tumor T-cell responses, immuno-checkpoint blockade and adoptive T-cell immunotherapy have recently achieved durable responses even in advanced cancer patients with metastases. Administration of antibodies on the T-cell surface, CTLA-4 and PD-1 (or PD-1 ligand PD-L1), resulted in tumor regression of not only melanoma and renal cell cancer which were known to be relatively sensitive to immunotherapy, but also various malignancies including lung, bladder, ovarian, gastric, and head and neck cancers, as well as hematological malignancies such as Hodgkin and B-cell malignant lymphomas. These findings have changed the status of immunotherapy in the development of cancer treatments. Currently, development of combinations employing cancer immunotherapy with immuno-checkpoint blockade, as well as personalized cancer immunotherapy based on the evaluation of pretreatment immune status, are in progress. PMID:26458459

  15. Pediatric investigation plans for specific immunotherapy: Questionable contributions to childhood health.

    PubMed

    Rose, Klaus; Kopp, Matthias Volkmar

    2015-12-01

    Allergen-specific immunotherapy (SIT) is the only disease-modifying treatment for children, adolescents, and adults with allergic diseases. The EU has a combined system of national and EU-wide marketing authorization for all medicines. Germany introduced a new therapy allergen ordinance in 2008. Allergen products manufacturers had to apply for marketing authorization application for the major allergen groups (grass group, birch group, mites group, bee/wasp venom). Due to the EU pediatric regulation, in force since 2007, manufacturers had also to submit a pediatric investigation plan (PIP) for each allergen product. We investigated the allergic rhinoconjunctivitis (ARC) standard PIP, developed jointly by the European Medicines Agency (EMA) and the German Paul Ehrlich Institut (PEI). We analyzed the 118 EMA PIP decisions, looked for SIT trials in children in www.clinicaltrials.gov, and further analyzed EMA/EU justifications. The PIPs request a 1-year dose-finding study in adults, a 5-year placebo-controlled (PC) efficacy & safety (E&S) study in adults, and a 5-year PC E&S study in children. Fifty-eight PIP development programs will have to be performed until 2031. But children benefit even more from SIT for ARC than adults. There is no convincing medical/scientific justification for PC E&S studies in children in the relevant EMA documents. The PIP requirement to withhold effective treatment to thousands of children in the placebo group over a 5-year period raises profound concerns. The EMA justifications are formalistic and lack scientific foundation. A critical academic review of the ARC PIPs and the entire PIP system is urgently needed. PMID:26495999

  16. Multifunctional nanoparticles for cancer immunotherapy.

    PubMed

    Saleh, Tayebeh; Shojaosadati, Seyed Abbas

    2016-07-01

    During the last decades significant progress has been made in the field of cancer immunotherapy. However, cancer vaccines have not been successful in clinical trials due to poor immunogenicity of antigen, limitations of safety associated with traditional systemic delivery as well as the complex regulation of the immune system in tumor microenvironment. In recent years, nanotechnology-based delivery systems have attracted great interest in the field of immunotherapy since they provide new opportunities to fight the cancer. In particular, for delivery of cancer vaccines, multifunctional nanoparticles present many advantages such as targeted delivery to immune cells, co-delivery of therapeutic agents, reduced adverse outcomes, blocked immune checkpoint molecules, and amplify immune activation via the use of stimuli-responsive or immunostimulatory materials. In this review article, we highlight recent progress and future promise of multifunctional nanoparticles that have been applied to enhance the efficiency of cancer vaccines. PMID:26901287

  17. Emerging immunotherapy in pediatric lymphoma.

    PubMed

    Erker, Craig; Harker-Murray, Paul; Burke, Michael J

    2016-01-01

    Hodgkin and non-Hodgkin lymphoma collectively are the third most common cancer diagnosed in children each year. For children who relapse or have refractory disease, outcomes remain poor. Immunotherapy has recently emerged as a novel approach to treat hematologic malignancies. The field has been rapidly expanding over the past few years broadening its armamentarium which now includes monoclonal antibodies, antibody-drug conjugates and cellular therapies including bispecific T-cell engagers and chimeric antigen receptor-engineered T cells. Many of these agents are in their infancy stages and only beginning to make their mark on lymphoma treatment while others have begun to show promising efficacy in relapsed disease. In this review, the authors provide an overview of current and emerging immunotherapies in the field of pediatric lymphoma. PMID:26616565

  18. Lentiviral vectors in cancer immunotherapy.

    PubMed

    Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

    2015-01-01

    Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy. PMID:25804479

  19. Current status of mold immunotherapy.

    PubMed

    Dhillon, M

    1991-05-01

    There is evidence to suggest that molds can cause IgE-mediated upper respiratory tract disorders and immunotherapy is efficacious in a select group. The environmental sampling studies show a remarkably small numbers of molds accounting for a majority of the mold load in various diverse locations. These are Cladosporium, Basidiospores, Aspergillus, and Alternaria-Penicillin families. Basidiospores have been underreported in the older studies because of difficulties in their identification. Whether the absolute mold level is the most important factor leading to IgE formation and induction of upper respiratory tract symptoms is uncertain. Certainly, the majority of the studies are based on the assumption that the absolute level of mold in the environment is the most important factor leading to the development of symptoms, but this is not based on strong evidence. A major problem in the majority of the studies is a lack of standardization of extracts which may lead to false negatives on skin testing and thus produce variable data in population evaluations comparing the prevalence of mold to its ability to induce IgE production and symptoms. The best current trials to document the efficacy of mold immunotherapy have been with the standardized Cladosporium extract. Unfortunately, these results cannot be extrapolated to the commercially available mold extracts available in the United States either for immunotherapy or for skin testing. These extracts are highly variable in their potency, prone to high false negative rates, and at best serve as poor skin testing reagents and possibly even worse immunotherapy reagents. Adequately standardized mold reagents are urgently needed to determine whether the Cladosporium data can be extrapolated to them in any meaningful way. PMID:2035901

  20. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    PubMed

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome. PMID:26022861

  1. Food Allergens in Mattress Dust in Norwegian Homes - A Potentially Important Source of Allergen Exposure

    PubMed Central

    Bertelsen, Randi J.; Fæste, Christiane K.; Granum, Berit; Egaas, Eliann; London, Stephanie J.; Carlsen, Kai-Håkon; Carlsen, Karin C. Lødrup; Løvik, Martinus

    2014-01-01

    Background Sensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment. Objective To describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13 year old adolescents, and secondly to identify home characteristics associated with the presence of food allergen contamination in dust. Methods Food allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analyzed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models. Results Fish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (<100m2) than larger dwellings (≥130 m2); 63-71% of the small dwellings (n=24) had milk, peanut, and fish allergens in the samples compared to 33-44% of the larger dwellings (n=95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors; with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens. Conclusions and clinical relevance Food allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spend in the bedroom, mattress dust may be an important source of exposure to food allergens. PMID:24304208

  2. Novel immunotherapies in lymphoid malignancies.

    PubMed

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE(®)) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  3. Viral vectors for cancer immunotherapy.

    PubMed

    Harrop, Richard; Carroll, Miles W

    2006-01-01

    Over the last decade, immunotherapy approaches for the treatment of cancer have been investigated with renewed vigour, perhaps catalyzed by the clinical successes seen with monoclonal antibody and cytokine based therapies. The identification of tumor-associated antigens (TAAs) in multiple cancer types has enabled the development of targeted immunotherapies and allayed some of the safety concerns associated with the induction of deleterious autoimmune reactions. In addition to the TAA or therapeutic gene, the antigen delivery system is equally as important for the development of a successful cancer vaccine. One approach to induce a potent and targeted antitumor response is to use viruses to deliver the TAA to cells of the immune system. A diverse array of oncolytic viruses and recombinant viral vectors encoding numerous therapeutic genes or TAAs have been tested in pre-clinical studies and produced results which, in some cases, justify their clinical development as potential cancer immunotherapies. Within the last 5-10 years, many such recombinant vectors have made the transition from pre-clinical research to clinical development and it is these, which are given most weight in this review. PMID:16146772

  4. Novel immunotherapies in lymphoid malignancies

    PubMed Central

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J.; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted ‘breakthrough’ designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  5. Immunotherapy Targets in Pediatric Cancer

    PubMed Central

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

    2011-01-01

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

  6. [Significance of inhaled environmental allergens].

    PubMed

    Zochert, J

    1983-01-01

    Whereas the importance of pollen as inhalative allergens has been largely investigated and is generally known, the experience in the frequency and the role of the sensibilization with air-borne fungi is relatively limited. In 720 patients with Asthma bronchiale the degree of sensitization has been tested with various extracts of air-borne fungi of SSW Dresden (mould mixture, aspergillin, mucor, cladosporium and penicillium and alternaria). The most frequent and also the strongest reactions were found with alternaria and the smallest part of positive skin reactions with penicillium. An isolated sensitization with mould has been demonstrated in 20 per cent of the cases. In 60 per cent of the tested patients a manifest mould allergy was shown by means of the Inhalative Allergen Test, the most favourable correlation between Intracutaneous Test (ICT) and Inhalative Test (IAT) was found with alternaria (76%). A conformance between ICT and basophils degranulation test (BDT) was stated in 69% of the cases. The aim should be comparable tests with allergen extracts without irritative effects and qualitative measurements of air-borne fungi. PMID:6649704

  7. Parasites and immunotherapy: with or against?

    PubMed

    Yousofi Darani, Hossein; Yousefi, Morteza; Safari, Marzieh; Jafari, Rasool

    2016-06-01

    Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewed. PMID:27413282

  8. Prevention of Birch Pollen-Related Food Allergy by Mucosal Treatment with Multi-Allergen-Chimers in Mice

    PubMed Central

    Hoflehner, Elisabeth; Hufnagl, Karin; Schabussova, Irma; Jasinska, Joanna; Hoffmann-Sommergruber, Karin; Bohle, Barbara; Maizels, Rick M.; Wiedermann, Ursula

    2012-01-01

    Background Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy. Methodology BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization. Results Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer. Conclusion Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy. PMID:22768077

  9. Cockroach allergen exposure and risk of asthma.

    PubMed

    Do, D C; Zhao, Y; Gao, P

    2016-04-01

    Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins have provided a basis for studying the mechanisms regarding cockroach allergen-induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen-presenting cell (APC) function in T-cell polarization, and cytokine production. Environmental pollutants, which often coexist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergen-induced innate immune responses, and the genetic basis for cockroach sensitization. PMID:26706467

  10. [Hymenoptera venom allergy. Analysis of double sensitization to wasp and bee venom in own material--diagnosis and classification for immunotherapy].

    PubMed

    Stobiecki, Marcin; Dyga, Wojciech; Czarnobilska, Ewa

    2013-01-01

    According to scientific societies guidelines the indication for venom immunotherapy is based on the clinical history of the patient. Diagnostic tests, like skin prick test or specific IgE serum estimation are conduct to prove IgE dependent mechanism of allergy and insect identification. Recent guidelines indicates for group of patients with severe systemic reactions as a candidates for diagnostic testing and in consequence for immunotherapy. In some countries diagnostic tests are also performed in patient who have a history of large local reactions, if they are considered as a candidates for immunotherapy. Double sensitization in cases of patients unable to identify the culprit insect is a diagnostic and therapeutic problem. In our group of patients (n = 113) we confirmed the double sensitization in 30% cases. The addition of a major allergen labeling reduced the number of people actually double-sensitized to 8.84%. It was observed that in patients who are not able to identify insect double sensitization phenomenon is particularly frequent as much as 45.5% and in the determination of the major allergens in 18.2%. Such patients needed detailed diagnosis and in many cases the use of two vaccines to conduct immunotherapy. PMID:24720122

  11. Sublingual Immunotherapy for Asthmatic Children Sensitized to House Dust Mite

    PubMed Central

    Liao, Wei; Hu, Qi; Shen, Lei-Lei; Hu, Ying; Tao, Hai-feng; Li, Hui-fan; Fan, Wen-ting

    2015-01-01

    Abstract The house dust mite is one of the most common allergens worldwide. There is good evidence that house dust mite subcutaneous immunotherapy is efficacious and has long-term benefit in children. However, the evidence of the benefit of house dust mite sublingual immunotherapy (SLIT) is less convincing. The purpose of this meta-analysis was to evaluate that efficacy and safety of dust mite SLIT in children with asthma. Medical Literature Analysis and Retrieval System Online, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials databases until February 2014 were searched. The primary outcome was mean change in asthma symptom score. Secondary outcomes included mean change in serum immunoglobulin G4 (sIgG4), specific Dermatophagoides pteronyssinus, immunoglobulin E (IgE) levels, and medication score. Safety was also assessed. We found that SLIT significantly decreased asthma symptom score (P = 0.007) and increased sIgG4 levels (P = 0.011) greater than control in children (<18 years of age) with asthma. There was no difference between SLIT and control groups in specific D pteronyssinus IgE levels (P = 0.076) and medication score (P = 0.408). The safety profile was similar between groups. Our study indicates that dust mite SLIT therapy was effective in reducing asthma symptoms and in increasing sIgG4 but did not significantly reduce medication scores or specific D pteronyssinus IgE levels. Our findings are not enough to support the use of dust mite SLIT in children with asthma.

  12. Improving the safety of oral immunotherapy for food allergy.

    PubMed

    Vazquez-Ortiz, Marta; Turner, Paul J

    2016-03-01

    Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health-related quality of life. In the last decade, research into disease-modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks-months. OIT has proven effective to induce immune modulation and 'desensitization' - that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short- and long-term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long-term adherence is unclear, which rises concerns given the low rates of long-term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti-IgE, pre-/probiotics). Biomarkers of safe/successful OIT are also under investigation. PMID:26593873

  13. Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity

    PubMed Central

    Wai, Christine Y. Y.; Leung, Nicki Y. H.; Ho, Marco H. K.; Gershwin, Laurel J.; Shu, Shang An; Leung, Patrick S. C.; Chu, Ka Hou

    2014-01-01

    Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy. PMID:25365343

  14. [In Process Citation].

    PubMed

    Konradsen, Jon; Arvidsson, Monica

    2016-01-01

    Allergen immunotherapy (AIT) to patients with allergy towards pollens, cats or house dust mite provides longstanding improvement of symptoms of rhinoconjunctivitis and allergic asthma and reduces the need for symptomatic medication. In addition, some studies suggest that AIT can protect from the development of asthma in children with allergic rhinitis. The clinical effects of AIT are explained by a shift from a Th2 to a Th1-mediated immune response upon allergen exposure. In Sweden the treatment is given as sublingual tablets (grass) or subcutaneous injections, and a treatment period of 3-4 years is necessary to ensure longstanding effect of the treatment. Serious side-effects such as asthma attacks or anaphylaxis are uncommon, if the treatment is provided by staff specifically trained to administer AIT. Intralymphatic administration of the allergen extract is a novel and promising approach that might shorten the treatment period with similar clinical effects. PMID:27046757

  15. Transcutaneous immunotherapy via laser-generated micropores efficiently alleviates allergic asthma in Phl p 5–sensitized mice

    PubMed Central

    Bach, D; Weiss, R; Hessenberger, M; Kitzmueller, S; Weinberger, E E; Krautgartner, W D; Hauser-Kronberger, C; Boehler, C; Thalhamer, J; Scheiblhofer, S

    2012-01-01

    Abstract Background Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser-generated micropores to subcutaneous injection. Methods BALB/c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen Phl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant-free Phl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; Phl p 5–specific serum levels of IgG1, IgG2a, and IgE; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed. Results Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in Th2-associated cytokine secretion, transcutaneous application revealed a general downregulation of Th1/Th2/Th17 responses. Successful therapy was associated with induction of IgG2a and an increase in FOXP3+ CD4+ T cells. Conclusions Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy-associated boosting of systemic Th2 immunity. Immunotherapy via laser-microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy. PMID:22947064

  16. Evaluating variability of allergens in commodity crops.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crops with significant food allergen issues, include legumes, peanut and soybean, cereal grains, such as wheat and maize, and tree nuts (walnut, Brazil nut, among other phylogenetically diverse species) (Teuber et al. 2006). Officially recognized allergenic proteins may include one or multiple prot...

  17. Reducing food allergenicity at the molecular level.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Food allergens are a significant worldwide public health issue. Estimates for the prevalence of food allergies are around 1-2 % of the total population and up to 8 % of children; although, the prevalence may vary between populations and age groups. Peanuts are one of the most allergenic foods. The...

  18. Neoantigen-based cancer immunotherapy.

    PubMed

    Bobisse, Sara; Foukas, Periklis G; Coukos, George; Harari, Alexandre

    2016-07-01

    Emerging clinical evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy in all cancer types. Recent clinical data clearly demonstrated that human tumor cells express antigenic peptides (epitopes) that can be recognized by autologous tumor-specific T cells and that enhancement of such immune reactivity can potentially lead to cancer control and cancer regression in patients with advanced disease. However, in most cases, it is unclear which tumor antigens (Ags) mediated cancer regression. Mounting evidence indicates that numerous endogenous mutated cancer proteins, a hallmark of tumor cells, can be processed into peptides and presented on the surface of tumor cells, leading to their immune recognition in vivo as "non-self" or foreign. Massively parallel sequencing has now overcome the challenge of rapidly identifying the comprehensive mutational spectrum of individual tumors (i.e., the "mutanome") and current technologies, as well as computational tools, have emerged that allow the identification of private epitopes derived from their mutanome and called neoantigens (neoAgs). On this basis, both CD4(+) and CD8(+) neoantigen-specific T cells have been identified in multiple human cancers and shown to be associated with a favorable clinical outcome. Notably, emerging data also indicate that neoantigen recognition represents a major factor in the activity of clinical immunotherapies. In the post-genome era, the mutanome holds promise as a long-awaited 'gold mine' for the discovery of unique cancer cell targets, which are exclusively tumor-specific and unlikely to drive immune tolerance, hence offering the chance for highly promising clinical programs of cancer immunotherapy. PMID:27563649

  19. Neoantigen-based cancer immunotherapy

    PubMed Central

    Bobisse, Sara; Coukos, George; Harari, Alexandre

    2016-01-01

    Emerging clinical evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy in all cancer types. Recent clinical data clearly demonstrated that human tumor cells express antigenic peptides (epitopes) that can be recognized by autologous tumor-specific T cells and that enhancement of such immune reactivity can potentially lead to cancer control and cancer regression in patients with advanced disease. However, in most cases, it is unclear which tumor antigens (Ags) mediated cancer regression. Mounting evidence indicates that numerous endogenous mutated cancer proteins, a hallmark of tumor cells, can be processed into peptides and presented on the surface of tumor cells, leading to their immune recognition in vivo as “non-self” or foreign. Massively parallel sequencing has now overcome the challenge of rapidly identifying the comprehensive mutational spectrum of individual tumors (i.e., the “mutanome”) and current technologies, as well as computational tools, have emerged that allow the identification of private epitopes derived from their mutanome and called neoantigens (neoAgs). On this basis, both CD4+ and CD8+ neoantigen-specific T cells have been identified in multiple human cancers and shown to be associated with a favorable clinical outcome. Notably, emerging data also indicate that neoantigen recognition represents a major factor in the activity of clinical immunotherapies. In the post-genome era, the mutanome holds promise as a long-awaited ‘gold mine’ for the discovery of unique cancer cell targets, which are exclusively tumor-specific and unlikely to drive immune tolerance, hence offering the chance for highly promising clinical programs of cancer immunotherapy. PMID:27563649

  20. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  1. Oral Immunotherapy for Food Allergy.

    PubMed

    Burbank, Allison J; Sood, Puja; Vickery, Brian P; Wood, Robert A

    2016-02-01

    Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut. PMID:26617227

  2. In-line inspection method with AIT-II and ADC

    NASA Astrophysics Data System (ADS)

    Terryll, Kathleen; Mateos, Carlos

    2001-04-01

    In this article, we emphasize the streamlined, in-line inspection methodology at Agere Systems, Madrid, Spain (formally Lucent Technologies, Microelectronics). This method includes the use of AIT-II with Impact ADC 2.0 to better focus and separate out excursion and baseline events. Real life examples demonstrating the potential of ADC are presented. In continuation, the shop reaction methodology and data flow scheme is described in detail. Currently, the Agere systems methodology is one of the most advanced in the European semiconductor industry.

  3. Adverse Events During Immunotherapy Against Grass Pollen-Induced Allergic Rhinitis - Differences Between Subcutaneous and Sublingual Treatment.

    PubMed

    Aasbjerg, Kristian; Dalhoff, Kim Peder; Backer, Vibeke

    2015-08-01

    Allergic rhinitis (AR) triggered by grass pollen is a common disease, affecting millions of people worldwide. Treatment consists of symptom-alleviating drugs, such as topical corticosteroids or antihistamines. Another option is potentially curative immunotherapy, currently available as sublingual and subcutaneous treatment. We investigated the potential differences in the prevalence and severity of adverse events related to subcutaneous and sublingual immunotherapy (SLIT) against grass pollen-induced AR. A thorough literature search was performed with PubMed and EMBASE. The findings were compared with the available summaries of product characteristics (SPC) and with commercial pharmacology databases (Micromedex). The majority of available safety data originate from registered products of standardized allergens. A surprisingly large percentage of drugs, especially those used in the United States, have no systematically collected safety data. No sufficiently powered randomized trials comparing sublingual and subcutaneous immunotherapy (SCIT) were available, but general safety assessments indicate that sublingual tablet treatment is safer than subcutaneous treatment. Not all commonly used immunotherapy drugs are officially registered, and not all have systematically collected safety data. This is especially true for older drugs used in the United States. In contrast, newer drugs that have undergone extensive clinical testing have better documentation, but unified collection of safety data is still lacking. Considering the evidence available, most drugs elicit similar side effects from the same organ systems, and symptoms from the sublingual drug classes are probably less severe. However, a head-to-head comparison of safety and efficacy is lacking. PMID:25968654

  4. Hymenoptera allergens: from venom to "venome".

    PubMed

    Spillner, Edzard; Blank, Simon; Jakob, Thilo

    2014-01-01

    In Western Europe, Hymenoptera venom allergy (HVA) primarily relates to venoms of the honeybee and the common yellow jacket. In contrast to other allergen sources, only a few major components of Hymenoptera venoms had been characterized until recently. Improved expression systems and proteomic detection strategies have allowed the identification and characterization of a wide range of additional allergens. The field of HVA research has moved rapidly from focusing on venom extract and single major allergens to a molecular understanding of the entire "venome" as a system of unique and characteristic components. An increasing number of such components has been identified, characterized regarding function, and assessed for allergenic potential. Moreover, advanced expression strategies for recombinant production of venom allergens allow selective modification of molecules and provide insight into different types of immunoglobulin E reactivities and sensitization patterns. The obtained information contributes to an increased diagnostic precision in HVA and may serve for monitoring, re-evaluation, and improvement of current therapeutic strategies. PMID:24616722

  5. Effect of high-dose sublingual immunotherapy on respiratory infections in children allergic to house dust mite

    PubMed Central

    Barberi, Salvatore; Verduci, Elvira; D'Auria, Enza; Poli, Piercarlo; Pietra, Benedetta; Incorvaia, Cristoforo; Buttafava, Serena; Frati, Franco; Riva, Enrica

    2015-01-01

    Background Allergic rhinitis is characterized by eosinophil inflammation. Allergic inflammation may induce susceptibility to respiratory infections (RI). House dust mite (HDM) sensitization is very frequent in childhood. Allergen immunotherapy may cure allergy as it restores a physiologic immune and clinical tolerance to allergen and exerts anti-inflammatory activity. Objective This study investigated whether six-month high-dose, such as 300 IR (index of reactivity), HDM-sublingual immunotherapy (SLIT) could affect RI in allergic children. Methods Globally, 40 HDM allergic children (18 males; mean age, 9.3 years) were subdivided in 2 groups: 20 treated by symptomatic drugs (group 1) and 20 by high-dose HDM-SLIT (group 2), since September 2012 to April 2013. The daily maintenance dose of HDM-SLIT was 4 pressures corresponding to 24, 4.8, and 60 µg, respectively of the major allergens Dermatophagoides pteronyssinus (Der p) 1, Der p 2, and Dermatophagoides farinae (Der f) 1. RI was diagnosed when at least 2 symptoms or signs, and fever were present for at least 48 hours. A family pediatrician provided diagnosis on a clinical ground. Results SLIT-treated children had significantly (p = 0.01) less RI episodes (3.5) than control group (5.45). About secondary outcomes, SLIT-treated children had less episodes of pharyngo-tonsillitis (p < 0.05) and bronchitis (p < 0.005), and snoring (p < 0.05) than control group. In addition, SLIT-treated children had less fever (p < 0.01) and took fewer medications, such as antibiotics (p < 0.05) and fever-reducers (p < 0.01), than control group. Conclusion This preliminary study might suggest that also a short course (6 months) of high-dose SLIT, titrated in µg of major allergens, could reduce RI in allergic children. PMID:26240793

  6. Induction of Allergic Responses to Peanut Allergen in Sheep

    PubMed Central

    Van Gramberg, Jenna L.; de Veer, Michael J.; O'Hehir, Robyn E.; Meeusen, Els N. T.; Bischof, Robert J.

    2012-01-01

    Peanut allergy is the leading cause of deaths due to food-induced anaphylaxis but despite continued research, there are currently no specific treatments available. Challenge testing is limited in patients due to the high risk of adverse reactions, emphasising the need for an appropriate animal model. In the present study we examine the induction of allergic responses in a sheep model for peanut allergy. Sheep were sensitised with peanut (PN) extract and in separate injections with ovalbumin (OVA) or house dust mite (HDM) extract. Serum PN-specific IgE responses were detected in 40–50% of immunised sheep, while only 10% (1 of 10 sheep) showed detectable OVA-specific IgE. All PN-allergic sheep tested showed an Ara h 1-specific IgE response, while four out of five allergic sheep showed an Ara h 2-specific IgE response. Animals with high serum IgE levels to HDM were also PN IgE-positive. Of the PN-sensitised animals with high PN-specific IgE, 80% also showed an immediate hypersensitivity reaction following an intradermal PN injection. This new large animal model of peanut allergy may provide a useful tool for future investigations of allergen-associated immune mechanisms and specific immunotherapy. PMID:23284686

  7. Novel immunotherapies for hematological malignancies

    PubMed Central

    Nelson, Michelle H.; Paulos, Chrystal M.

    2014-01-01

    Summary The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise the state of the art in immunotherapy with a focus on strategies that exploit the patient’s immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematological malignancies, including (i) conventional monoclonal therapies like rituximab, (ii) engineered monoclonal antibodies called bispecific T cell engagers (BiTEs), (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4 and IDO), and (iv) adoptive cell transfer (ACT) therapy with T cells engineered to express chimeric antigen receptors (CARs) or T-cell receptors (TCRs). We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

  8. Novel approaches in cancer immunotherapy.

    PubMed

    Subramaniam, Deepa S; Liu, Stephen V; Giaccone, Giuseppe

    2016-04-01

    Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccines, tumor cell vaccines and immune cell vaccines. The pros and cons of nucleic acid-based vaccines including DNA and RNA vaccines will be discussed. Adoptive cell therapy has made significant progress utilizing chimeric antigen-receptor transduced T cells, especially in hematologic malignancies. We will also consider the key targets in checkpoint inhibition, and summarize some of the preclinical and clinical data with respect to checkpoint inhibition. Progress made in the novel immunotherapeutic approach of oncolytic viral therapy will be analyzed. PDL-1 expression by tumor cells and tumor infiltrating lymphocytes has been looked at as a biomarker in clinical trials. Limitations to such an approach and potential candidates for future predictive biomarkers of response to immunotherapy and biomarkers of autoimmunity and adverse reactions will be considered. PMID:27232512

  9. Adoptive immunotherapy against ovarian cancer.

    PubMed

    Mittica, Gloria; Capellero, Sonia; Genta, Sofia; Cagnazzo, Celeste; Aglietta, Massimo; Sangiolo, Dario; Valabrega, Giorgio

    2016-01-01

    The standard front-line therapy for epithelial ovarian cancer (EOC) is combination of debulking surgery and platinum-based chemotherapy. Nevertheless, the majority of patients experience disease recurrence. Although extensive efforts to find new therapeutic options, cancer cells invariably develop drug resistance and disease progression. New therapeutic strategies are needed to improve prognosis of patients with advanced EOC.Recently, several preclinical and clinical studies investigated feasibility and activity of adoptive immunotherapy in EOC. Our aim is to highlight prospective of adoptive immunotherapy in EOC, focusing on HLA-restricted Tumor Infiltrating Lymphocytes (TILs), and MHC-independent immune effectors such as natural killer (NK), and cytokine-induced killer (CIK). Adoptive cell therapy (ACT) has shown activity in several pre-clinical models. Available preclinical and clinical data suggest that adoptive cell therapy may provide the best benefit in settings of low tumor burden, minimal residual disease, or maintenance therapy. Further studies are needed to better define the optimal clinical setting. PMID:27188274

  10. [Dendritic cells in cancer immunotherapy].

    PubMed

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities. PMID:26486534

  11. Allergen Atlas: a comprehensive knowledge center and analysis resource for allergen information

    PubMed Central

    Tong, Joo Chuan; Lim, Shen Jean; Muh, Hon Cheng; Chew, Fook Tim; Tammi, Martti T.

    2009-01-01

    Summary: A variety of specialist databases have been developed to facilitate the study of allergens. However, these databases either contain different subsets of allergen data or are deficient in tools for assessing potential allergenicity of proteins. Here, we describe Allergen Atlas, a comprehensive repository of experimentally validated allergen sequences collected from in-house laboratory, online data submission, literature reports and all existing general-purpose and specialist databases. Each entry was manually verified, classified and hyperlinked to major databases including Swiss-Prot, Protein Data Bank (PDB), Gene Ontology (GO), Pfam and PubMed. The database is integrated with analysis tools that include: (i) keyword search, (ii) BLAST, (iii) position-specific iterative BLAST (PSI-BLAST), (iv) FAO/WHO criteria search, (v) graphical representation of allergen information network and (vi) online data submission. The latest version contains information of 1593 allergen sequences (496 IUIS allergens, 978 experimentally verified allergens and 119 new sequences), 56 IgE epitope sequences, 679 links to PDB structures and 155 links to Pfam domains. Availability: Allergen Atlas is freely available at http://tiger.dbs.nus.edu.sg/ATLAS/. Contact: martti@nus.edu.sg. PMID:19213741

  12. Effects of NO2 and Ozone on Pollen Allergenicity

    PubMed Central

    Frank, Ulrike; Ernst, Dieter

    2016-01-01

    This mini-review summarizes the available data of the air pollutants NO2 and ozone on allergenic pollen from different plant species, focusing on potentially allergenic components of the pollen, such as allergen content, protein release, IgE-binding, or protein modification. Various in vivo and in vitro studies on allergenic pollen are shown and discussed. PMID:26870080

  13. Using magnetic beads to reduce reanut allergens from peanut extracts.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ferric irons (Fe3+) and phenolic compounds have been shown to bind to peanut allergens. An easy way to isolate peanut allergens is by use of magnetic beads attached with or without phenolics to capture peanut allergens or allergen-Fe3+ complexes, thus, achieving the goal of producing peanut extracts...

  14. Effects of NO2 and Ozone on Pollen Allergenicity.

    PubMed

    Frank, Ulrike; Ernst, Dieter

    2016-01-01

    This mini-review summarizes the available data of the air pollutants NO2 and ozone on allergenic pollen from different plant species, focusing on potentially allergenic components of the pollen, such as allergen content, protein release, IgE-binding, or protein modification. Various in vivo and in vitro studies on allergenic pollen are shown and discussed. PMID:26870080

  15. Safety of a peanut oral immunotherapy protocol in peanut allergic children

    PubMed Central

    Hofmann, Alison M.; Scurlock, Amy M.; Jones, Stacie M.; Palmer, Kricia P.; Lokhnygina, Yuliya; Steele, Pamela H.; Kamilaris, Janet; Burks, A. Wesley

    2009-01-01

    Background Oral immunotherapy offers a promising therapeutic option for peanut allergy. Given that during oral immunotherapy an allergic patient ingests an allergen that could potentially cause a serious reaction, safety of oral immunotherapy is of particular concern. Objective The purpose of this study is to examine safety during the initial escalation day, build-up phase, and home dosing phase in subjects enrolled in a peanut oral immunotherapy study. Methods Skin, upper respiratory, chest and abdominal symptoms were recorded with initial escalation day and build-up phase dosings. Subjects also maintained daily diaries detailing symptoms after each home dosing. A statistical analysis of this data was performed. Results Twenty of 28 patients completed all phases of the study. During the initial escalation day, upper respiratory (79%) and abdominal (68%) symptoms were the most likely symptoms experienced. The risk of mild wheezing during the initial escalation day was 18%. The probability of having any symptoms after a build-up phase dose was 46%, with a risk of 29% for upper respiratory symptoms and 24% for skin symptoms. The risk of reaction with any home dose was 3.5%. Upper respiratory (1.2%) and skin (1.1%) were the most likely symptoms after home doses. Treatment was given with 0.7% of home doses. Two subjects received epinephrine after one home dose each. Conclusions Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study. Allergic reactions with home doses were rare. PMID:19477496

  16. Role of regulatory B cells in immune tolerance to allergens and beyond.

    PubMed

    van de Veen, Willem; Stanic, Barbara; Wirz, Oliver F; Jansen, Kirstin; Globinska, Anna; Akdis, Mübeccel

    2016-09-01

    Immune tolerance to both self-antigens and innocuous non-self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion. However, IL-35 and TGF-β have also been associated with B cell-mediated immunosuppression. Several types of murine and human Breg cells have been described, such as mouse CD5(+)CD1d(hi) B10 cells, CD21(hi)CD23(hi)CD24(hi) transitional stage 2-like B cells, and CD138(+) plasma cells and plasmablasts. Human Breg cell types include CD27(+)CD24(high) B10 cells, CD24(hi)CD38(hi) immature transitional B cells, and CD73(-)CD25(+)CD71(+) BR1 cells and a subset of plasma cells. Support for the in vivo existence of allergen-specific human Breg cells comes from direct detection of their increase during the course of allergen-specific immunotherapy, as well as their increased expression in nonallergic but high-dose allergen-exposed beekeepers. Human BR1 cells selectively upregulate IgG4 antibodies on differentiation to plasma cells. This suggests an additional immune regulatory role because of the noninflammatory and blocking antibody function of IgG4. Taken together, Breg cells appear to be involved in mediating allergen tolerance, but many open questions remain to be answered. PMID:27596706

  17. Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody

    SciTech Connect

    Li, Mi; Gustchina, Alla; Alexandratos, Jerry; Wlodawer, Alexander; Wünschmann, Sabina; Kepley, Christopher L.; Chapman, Martin D.; Pomes, Anna

    2008-09-03

    The crystal structure of a 1:1 complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-{angstrom} resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-86, 98-100, and 129-132. Cation-{pi} interactions exist between Lys-65, Arg-83, and Lys-132 in Bla g 2 and several tyrosines in 7C11. In the complex with Fab', Bla g 2 forms a dimer, which is stabilized by a quasi-four-helix bundle comprised of an {alpha}-helix and a helical turn from each allergen monomer, exhibiting a novel dimerization mode for an aspartic protease. A disulfide bridge between C51a and C113, unique to the aspartic protease family, connects the two helical elements within each Bla g 2 monomer, thus facilitating formation of the bundle. Mutation of these cysteines, as well as the residues Asn-52, Gln-110, and Ile-114, involved in hydrophobic interactions within the bundle, resulted in a protein that did not dimerize. The mutant proteins induced less {beta}-hexosaminidase release from mast cells than the wild-type Bla g 2, suggesting a functional role of dimerization in allergenicity. Because 7C11 shares a binding epitope with IgE, the information gained by analysis of the crystal structure of its complex provided guidance for site-directed mutagenesis of the allergen epitope. We have now identified key residues involved in IgE antibody binding; this information will be useful for the design of vaccines for immunotherapy.

  18. Ultrasound-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum Ait.

    PubMed

    Xia, En-Qin; Yu, Ying-Ying; Xu, Xiang-Rong; Deng, Gui-Fang; Guo, Ya-Jun; Li, Hua-Bin

    2012-07-01

    Oleanolic acid and ursolic acid are the main bioactive compounds in fruit of Ligustrum lucidum Ait, which possess anti-inflammatory, antioxidative, antiprotozoal, antimutagenic and anticancer properties. In this study, the ultrasound-assisted extraction of oleanolic acid and ursolic acid from L. lucidum Ait was investigated with HPLC-photodiode array detection. Effects of several experimental parameters, such as type and concentration of extraction solvent, ratio of liquid to material, extraction temperature and extraction time, on extraction efficiencies of oleanolic acid and ursolic acid from L. lucidum were evaluated. The influence of experimental parameters on extraction efficiency of ursolic acid was more significant than that of oleanolic acid. The optimal extraction conditions were 95% ethanol, the ratio of material to liquid at 1:20, and extraction for 10 min at 40°C under ultrasonic irradiation. Under the optimal conditions, the yields of oleanolic acid and ursolic acid were 6.3 ± 0.25 and 9.8 ± 0.30 mg/g, respectively. The results indicated that the ultrasound-assisted extraction is a very useful method for the extraction of oleanolic acid and ursolic acid from L. lucidum. PMID:22197019

  19. Potentiality of immunotherapy against hepatocellular carcinoma

    PubMed Central

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  20. Agreement of skin test with IL-4 production and CD40L expression by T cells upon immunotherapy of subjects with systemic reactions to Hymenoptera stings.

    PubMed

    Urra, José M; Cabrera, Carmen M; Alfaya, Teresa; Feo-Brito, Francisco

    2016-02-01

    Venom immunotherapy is the only curative intervention for subjects with Hymenoptera venom allergy who suffering systemic reactions upon bee or wasp stings. Venom immunotherapy can restore normal immunity against venom allergens, as well as providing to allergic subjects a lifetime tolerance against venoms. Nevertheless, it is necessary using safety assays to monitoring the development of tolerance in the VIT protocols to avoid fatal anaphylactic reactions. The purpose of this study was to assess the modifications in several markers of tolerance induction in subjects with Hymenoptera venom allergy undergoing immunotherapy. The studies were performed at baseline time and after six month of VIT. Intradermal skin tests, basophil activation tests, specific IgE levels; and the T-cell markers (IL-4 and IFN-γ producing cells; and expression of the surface activation markers CD40L and CTLA-4) were assayed. At six month of immunotherapy all parameters studied had significant alterations. All decreased, except the IFN-γ producing cells. In addition, modifications in intradermal skin test showed a significant correlation with both, CD40L expression on CD4 T lymphocytes (p=0.043) and IL-4 producing T lymphocytes (p=0.012). Neither basophil activation test nor serum levels of sIgE demonstrated any correlation with the immunological parameters studied nor among them. These results suggest that both IL-4 production and CD40L expression could be two good indicators of the beneficial effects of venom immunotherapy which translate into skin tests. PMID:26774053

  1. Immunotherapy of Metastases Enhances Subsequent Chemotherapy

    NASA Astrophysics Data System (ADS)

    Hanna, Michael G.; Key, Marc E.

    1982-07-01

    In many multimodal therapies of cancer, postsurgical chemotherapy is administered before immunotherapy for treatment of micrometastatic disease. This sequence may not be the most efficacious. Experiments in which strain 2 guinea pigs bearing syngeneic L10 hepatocarcinomas were given immunotherapy showed that infiltrating immune effector cells not only were tumoricidal but disrupted the characteristically compact structure of metastatic foci. When cytotoxic drugs were administered at the peak of this inflammatory response, the survival rate of the guinea pigs increased significantly. We conclude that postsurgical immunotherapy can enhance the effect of cytotoxic drugs administered subsequently.

  2. Contact Dermatitis, Patch Testing, and Allergen Avoidance.

    PubMed

    Burkemper, Nicole M

    2015-01-01

    In patients presenting with a complaint of rash, contact dermatitis is often the underlying diagnosis making it an entity with which health care providers should be familiar. Contact dermatitis can be divided into irritant contact dermatitis and allergic contact dermatitis. In a patient suspected of having allergic contact dermatitis, patch testing can be done to identify specific allergens. Education focused on allergen avoidance and safe products is an integral part of treatment for the contact dermatitis patient. Knowledge of the most common allergens is helpful for clinicians to be able to provide this education. PMID:26455061

  3. Immunotherapy

    MedlinePlus

    ... Information Specialist Financial Support Online Chats Support Groups Peer-to-Peer Support LLS Community Blogs Caregiver Support Other Helpful ... Information Specialist Financial Support Online Chats Support Groups Peer-to-Peer Support LLS Community Blogs Caregiver Support ...

  4. Targeting neoantigens for cancer immunotherapy.

    PubMed

    Lu, Yong-Chen; Robbins, Paul F

    2016-07-01

    Studies first carried out in the 1980s have demonstrated murine T cells can recognize mutated gene products, known as neoantigens, and that these T cells are capable of mediating tumor rejection. The first human tumor antigens isolated in the early 1990s were the products of non-mutated genes expressed in a tissue-specific manner; subsequent studies have indicated that tumor-infiltrating lymphocytes that are cultured in vitro frequently recognize mutated gene products. In addition, correlative studies indicate that clinical responses to therapies involving the use of antibodies directed against checkpoint inhibitors such as CTLA-4 and PD-1 may be associated with mutational burden, providing indirect evidence that these responses may primarily be mediated by neoantigen-reactive T cells. The importance of neoantigen-reactive T cells may be elucidated by the results of ongoing and future studies aimed at leveraging information gained from mutational profiling to enhance the potency of immunotherapies. PMID:27208041

  5. [Current immunotherapy of multiple sclerosis].

    PubMed

    Paul, F; Ruprecht, K

    2015-08-01

    Following the introduction of interferon beta 1b as the first immunomodulatory therapy for multiple sclerosis (MS) in 1993, there are currently nine substances or substance classes approved for the treatment of MS (i.e. alemtuzumab, azathioprine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab and teriflunomide). Major developments during the last 5 years include the approval of orally administered medications (i.e. fingolimod, teriflunomide and dimethyl fumarate), a monoclonal antibody (alemtuzumab), as well as glatiramer acetate with an administration frequency three times a week and a pegylated formulation of interferon beta 1a. The broadened therapeutic options enable a more differentiated and individualized therapy of MS; however, evidence-based data for therapeutic decision-making relevant in clinical practice are not always available. Rare but potentially severe and even life-threatening side effects of immunotherapies for MS require continuous pharmacovigilance and adherence to risk management plans. PMID:26253589

  6. [Aβ immunotherapy for Alzheimer's disease].

    PubMed

    Sakai, Kenji; Yamada, Masahito

    2013-04-01

    Alzheimer's disease (AD) is one of the neurodegenerative diseases characterized by the deposition of amyloid-β-protein (Aβ) as senile plaques in the brain parenchyma and phosphorylated-tau accumulation as neurofibrillary tangles in the neurons. Although details of the disease pathomechanisms remain unclear, Aβ likely acts as a key protein for AD initiation and progression, followed by abnormal tau phosphorylation and neuronal death (amyloid-cascade hypothesis). According to this hypothesis, Aβ immunization therapies are created to eliminate Aβ from the brain, and to prevent the neurons from damage by these pathogenic proteins. There are two methods for Aβ immunotherapies: active and passive immunization. Previous studies have shown Aβ removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. On the contrary, side effects emerged, such as meningoencephalitis, vasogenic edema, which are currently called amyloid related imaging abnormalities (ARIA)-E and microhemorrhage (ARIA-H). In neuropathological studies of immunized cases, Aβ was removed from the brain parenchyma and phosphorylated-tau was reduced in the neuronal processes. Moreover, deterioration of the cerebral amyloid angiopathy (CAA) and an increase of microhemorrhages and microinfarcts were described. Aβ is cleared from the brain mainly via the lymphatic drainage pathway. ARIA could stem from severe CAA due to dysfunction of the drainage pathway after immunotherapy. Aβ immunization has a potential of cure for AD patients, although the above-described problems must be overcome before applying this therapy in clinical treatment. PMID:23568994

  7. Who Will Benefit from Cancer Immunotherapy?

    Cancer.gov

    Researchers have identified a “genetic signature” in the tumors of patients with advanced melanoma who responded to a form of immunotherapy called checkpoint blockade. The results could be the basis for a test that identifies likely responders.

  8. Immune checkpoints and immunotherapy for colorectal cancer

    PubMed Central

    Singh, Preet Paul; Sharma, Piyush K.; Krishnan, Gayathri; Lockhart, A. Craig

    2015-01-01

    Colorectal cancer (CRC) remains one of the major causes of death worldwide, despite steady improvement in early detection and overall survival over the past decade. Current treatment paradigms, with chemotherapy and biologics, appear to have reached their maximum benefit. Immunotherapy, especially with checkpoint inhibitors, has shown considerable clinical benefit in various cancers, including mismatch-repair-deficient CRC. This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents, combinations and in conjunction with chemotherapy—in patients with CRC. This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC, as well as current efforts in CRC immunotherapy. PMID:26510455

  9. Immunotherapy: Disrupting the Cancer Treatment World

    MedlinePlus

    ... ACS » + - Text Size Immunotherapy: Disrupting the Cancer Treatment World By Elizabeth Mendes June 16, 2014 This story ... of cancer research in depth. The cancer research world is dedicating increasing energy to a rapidly evolving ...

  10. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the... capable of determining the good health of the animals. (iii) Immunization against tetanus. Animals of...

  11. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the... capable of determining the good health of the animals. (iii) Immunization against tetanus. Animals of...

  12. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the... capable of determining the good health of the animals. (iii) Immunization against tetanus. Animals of...

  13. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the... capable of determining the good health of the animals. (iii) Immunization against tetanus. Animals of...

  14. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the... capable of determining the good health of the animals. (iii) Immunization against tetanus. Animals of...

  15. Treatment of warts with contact allergens.

    PubMed

    Word, Andrew P; Nezafati, Kaveh A; Cruz, Ponciano D

    2015-01-01

    Contact immunotherapy is an increasingly used, effective means of treating cutaneous viral warts. Dinitrochlorobenzene, diphencyprone, and squaric acid dibutylester are the most frequently used modalities, showing slight variances in adverse effect profiles and efficacy. All of these agents serve as safe treatment modalities when administered according to the guidelines recommended herein. We review the value of contact immunotherapy in the treatment of cutaneous viral warts. PMID:25581668

  16. Defining the critical hurdles in cancer immunotherapy

    PubMed Central

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  17. Cancer Immunotherapy: A Treatment for the Masses

    NASA Astrophysics Data System (ADS)

    Blattman, Joseph N.; Greenberg, Philip D.

    2004-07-01

    Cancer immunotherapy attempts to harness the exquisite power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is clearly capable of recognizing and eliminating tumor cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for immunotherapy is to use advances in cellular and molecular immunology to develop strategies that effectively and safely augment antitumor responses.

  18. Analytical solution for haze values of aluminium-induced texture (AIT) glass superstrates for a-Si:H solar cells.

    PubMed

    Sahraei, Nasim; Forberich, Karen; Venkataraj, Selvaraj; Aberle, Armin G; Peters, Marius

    2014-01-13

    Light scattering at randomly textured interfaces is essential to improve the absorption of thin-film silicon solar cells. Aluminium-induced texture (AIT) glass provides suitable scattering for amorphous silicon (a-Si:H) solar cells. The scattering properties of textured surfaces are usually characterised by two properties: the angularly resolved intensity distribution and the haze. However, we find that the commonly used haze equations cannot accurately describe the experimentally observed spectral dependence of the haze of AIT glass. This is particularly the case for surface morphologies with a large rms roughness and small lateral feature sizes. In this paper we present an improved method for haze calculation, based on the power spectral density (PSD) function of the randomly textured surface. To better reproduce the measured haze characteristics, we suggest two improvements: i) inclusion of the average lateral feature size of the textured surface into the haze calculation, and ii) considering the opening angle of the haze measurement. We show that with these two improvements an accurate prediction of the haze of AIT glass is possible. Furthermore, we use the new equation to define optimum morphology parameters for AIT glass to be used for a-Si:H solar cell applications. The autocorrelation length is identified as the critical parameter. For the investigated a-Si:H solar cells, the optimum autocorrelation length is shown to be 320 nm. PMID:24922000

  19. Development and validation of 697 novel polymorphic genomic and EST-SSR Markers in the American cranberry (Vaccinium macrocarpon Ait.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The American cranberry, Vaccinium macrocarpon Ait., is an economically important North American fruit crop that is consumed because of its unique flavor and potential health benefits. However, a lack of abundant, genome-wide molecular markers has limited the adoption of modern molecular assisted sel...

  20. Oncolytic Immunotherapy for Treatment of Cancer.

    PubMed

    Tsun, A; Miao, X N; Wang, C M; Yu, D C

    2016-01-01

    Immunotherapy entails the treatment of disease by modulation of the immune system. As detailed in the previous chapters, the different modes of achieving immune modulation are many, including the use of small/large molecules, cellular therapy, and radiation. Oncolytic viruses that can specifically attack, replicate within, and destroy tumors represent one of the most promising classes of agents for cancer immunotherapy (recently termed as oncolytic immunotherapy). The notion of oncolytic immunotherapy is considered as the way in which virus-induced tumor cell death (known as immunogenic cancer cell death (ICD)) allows the immune system to recognize tumor cells and provide long-lasting antitumor immunity. Both immune responses toward the virus and ICD together contribute toward successful antitumor efficacy. What is now becoming increasingly clear is that monotherapies, through any of the modalities detailed in this book, are neither sufficient in eradicating tumors nor in providing long-lasting antitumor immune responses and that combination therapies may deliver enhanced efficacy. After the rise of the genetic engineering era, it has been possible to engineer viruses to harbor combination-like characteristics to enhance their potency in cancer immunotherapy. This chapter provides a historical background on oncolytic virotherapy and its future application in cancer immunotherapy, especially as a combination therapy with other treatment modalities. PMID:27240460

  1. Developments in immunotherapy for gastrointestinal cancer.

    PubMed

    Diaz, J L; Wanta, S M; Fishbein, T M; Kroemer, A

    2015-08-01

    Gastrointestinal (GI) cancers are the most commonly occurring cancer worldwide. Colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. Despite the advent of screening and the declining incidence of CRC overall, most patients are not diagnosed at an early, localized stage. Due to resistance to chemotherapy, recurrence, and metastatic disease, those diagnosed with advanced disease have only a 12% 5-year survival rate. Given the overwhelming global impact of CRC, the need for advanced therapy is crucial. Targeted immunotherapy in addition to surgical resection, traditional chemotherapy, and radiation therapy is on the rise. For the purpose of this review, we focused on the advances of immunotherapy, particularly in CRC, with mention of research pertaining to particular advances in immunotherapy for other aspects of the GI system. We review basic immunology and the microenvironment surrounding colorectal tumors that lead to immune system evasion and poor responses to chemotherapy. We also examined the way these obstacles are proving to be the targets of tumor specific immunotherapy. We will present current FDA approved immunotherapies such as monoclonal antibodies (mAb) targeting tumor specific antigens, as well as vaccines, adoptive cell therapy, cytokines, and check-point inhibitors. A summation of prior research, current clinical trials, and prospective therapies in murine models help delineate our current status and future strategies on CRC immunotherapy. PMID:25916195

  2. Next generation of food allergen quantification using mass spectrometric systems.

    PubMed

    Koeberl, Martina; Clarke, Dean; Lopata, Andreas L

    2014-08-01

    Food allergies are increasing worldwide and becoming a public health concern. Food legislation requires detailed declarations of potential allergens in food products and therefore an increased capability to analyze for the presence of food allergens. Currently, antibody-based methods are mainly utilized to quantify allergens; however, these methods have several disadvantages. Recently, mass spectrometry (MS) techniques have been developed and applied to food allergen analysis. At present, 46 allergens from 11 different food sources have been characterized using different MS approaches and some specific signature peptides have been published. However, quantification of allergens using MS is not routinely employed. This review compares the different aspects of food allergen quantification using advanced MS techniques including multiple reaction monitoring. The latter provides low limits of quantification for multiple allergens in simple or complex food matrices, while being robust and reproducible. This review provides an overview of current approaches to analyze food allergens, with specific focus on MS systems and applications. PMID:24824675

  3. Allergenicity attributes of different peanut market types.

    PubMed

    Koppelman, Stef J; Jayasena, Shyamali; Luykx, Dion; Schepens, Erik; Apostolovic, Danijela; de Jong, Govardus A H; Isleib, Thomas G; Nordlee, Julie; Baumert, Joe; Taylor, Steve L; Cheng, Hsiaopo; Maleki, Soheila

    2016-05-01

    Four different market classes of peanut (Runner, Virginia Spanish, and Valencia) are commonly consumed in Western countries, but for some consumers peanuts are a main cause of food-induced anaphylaxis. Limited information is available on the comparative allergenicity of these distinct market classes. The aim of this study was to compare allergenicity attributes of different peanut cultivars. The protein content and protein profiles were highly comparable for all tested cultivars. All cultivar samples contained the major allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6, as assessed by SDS-PAGE and RP-HPLC, although some minor differences in major allergen content were found between samples. All samples were reactive in commercial ELISAs for detection and quantification of peanut protein. IgE-binding potency differed between samples with a maximum factor of 2, indicating a highly comparable allergenicity. Based on our observations, we conclude that peanuts from the main market types consumed in Western countries are highly comparable in their allergenicity attributes, indicating that safety considerations with regard to peanut allergy are not dependent on the peanut cultivar in question. PMID:26921497

  4. Cross-reactivity of peanut allergens.

    PubMed

    Bublin, Merima; Breiteneder, Heimo

    2014-04-01

    Peanut seeds are currently widely used as source of human food ingredients in the United States of America and in European countries due to their high quality protein and oil content. This article describes the classification and molecular biology of peanut seed allergens with particular reference to their cross-reactivities. Currently, the IUIS allergen nomenclature subcommittee accepts 12 peanut allergens. Two allergens belong to the cupin and four to the prolamin superfamily, and six are distributed among profilins, Bet v 1-like proteins, oleosins, and defensins. Clinical observations frequently report an association of peanut allergy with allergies to legumes, tree nuts, seeds, fruits and pollen. Molecular cross-reactivity has been described between members of the Bet v 1-like proteins, the non-specific lipid transfer proteins, and the profilins. This review also addresses the less well-studied cross-reactivity between cupin and prolamin allergens of peanuts and of other plant food sources and the recently discovered cross-reactivity between peanut allergens of unrelated protein families. PMID:24554241

  5. Removing peanut allergens by tannic acid.

    PubMed

    Chung, Si-Yin; Reed, Shawndrika

    2012-10-01

    Tannic acid (TA) forms insoluble complexes with proteins. The aims here were to remove major peanut allergens as insoluble TA complexes and determine if they would dissociate and release the allergens at pH 2 and 8 (gut pH). Release of the allergens in the gut could lead to absorption and consequently an allergic reaction. TA (0.25, 0.5, 1, and 2 mg/ml) was added to a peanut butter extract (5 mg/ml; pH 7.2), stirred, and centrifuged. The precipitates were then suspended in buffer at pH 2, centrifuged, re-suspended at pH 8, and centrifuged. Supernatants from each step were analysed by SDS-PAGE, ELISA, and Western blots. The effect of NaCl (1M) on complexes was also determined. Results showed that complexes formed at a TA concentration >0.5 mg/ml did not release major peanut allergens at pH 2 and 8, regardless of 1M NaCl being present or not. IgE binding of the extracts was reduced substantially, especially at a TA concentration of 1-2 mg/ml. Animal or clinical studies are still needed before TA can find an application in the development of low-allergen peanut products/beverages or the removal of peanut allergens due to accidental ingestion. PMID:25005968

  6. Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

    SciTech Connect

    Yang, Marie; Mine, Yoshinori

    2009-01-09

    The identification of food allergen T-cell epitopes provides a platform for the development of novel immunotherapies. Despite extensive knowledge of the physicochemical properties of hen ovalbumin (OVA), a major egg allergen, the complete T-cell epitope map of OVA has surprisingly not been defined in the commonly used BALB/c mouse model. In this study, spleen cells obtained from OVA-sensitized mice were incubated in the presence of 12-mer overlapping synthetic peptides, constructed using the SPOTS synthesis method. Proliferative activity was assessed by 72-h in vitro assays with use of the tetrazolium salt WST-1 and led to identification of four mitogenic sequences, i.e., A39R50, S147R158, K263E274, and A329E340. ELISA analyses of interferon (IFN)-{gamma} and interleukin (IL)-4 productions in cell culture supernatants upon stimulation with increasing concentrations of peptides confirmed their immunogenicity. Knowledge of the complete T-cell epitope map of OVA opens the way to a number of experimental investigations, including the exploration of peptide-based immunotherapy.

  7. Cytochemical localization of some hydrolases in the pollen and pollen tubes of Amaryllis vittata Ait.

    PubMed

    Sharma, D

    1982-01-01

    Some hydrolases are localized cytochemically in the pollen and pollen tubes of Amaryllis vittata Ait. The function of different enzymes is discussed in relation to pollen tubes morphogenesis. Activity of most of the enzymes was confined to colpus region, pollen wall and general cytoplasm of pollen and pollen tube. The activity of hydrolytic enzymes like acid monophosphoesterase and lipase and was nil in the exine of both germinated and ungerminated pollen, whereas intense reaction for esterase was observed in exine. Enzyme activity increased after germination which suggest the hydrolysis of stored metabolites and synthesis of proteins and other metabolites for the active growth of pollen tube. Intense reaction for enzymes like alkaline phosphomonoesterase, ATP-ase, 5-nucleotidase etc. at the tip region of pollen tube suggest their role in physiological processes associated with exchange of materials through intercellular transport during tube wall polysaccharide biogenesis. PMID:6298081

  8. Passive immunotherapy in the treatment of advanced human immunodeficiency virus infection.

    PubMed

    Jacobson, J M; Colman, N; Ostrow, N A; Simson, R W; Tomesch, D; Marlin, L; Rao, M; Mills, J L; Clemens, J; Prince, A M

    1993-08-01

    To evaluate the safety and efficacy of passive immunotherapy for advanced human immunodeficiency virus (HIV) infection, a randomized, double-blind, controlled trial of human anti-HIV hyperimmune plasma was conducted. Sixty-three subjects with stage IV HIV disease (AIDS) were randomized to received 250 mL of either HIV-immune plasma or HIV antibody-negative plasma every 4 weeks. Although nonsignificant trends toward improved survival and delayed occurrence of a new opportunistic infection were noted, no significant effects on absolute CD4 lymphocyte counts or quantitative HIV viremia were seen. The only notable toxicity was the allergenicity to be expected from infusing plasma products, usually manifesting as urticaria. Thus, results do not rule out the potential usefulness of passive immunization with different preparations, but did fail to demonstrate clinical benefit of the product studied. PMID:8101550

  9. MutAIT: an online genetic toxicology data portal and analysis tools.

    PubMed

    Avancini, Daniele; Menzies, Georgina E; Morgan, Claire; Wills, John; Johnson, George E; White, Paul A; Lewis, Paul D

    2016-05-01

    Assessment of genetic toxicity and/or carcinogenic activity is an essential element of chemical screening programs employed to protect human health. Dose-response and gene mutation data are frequently analysed by industry, academia and governmental agencies for regulatory evaluations and decision making. Over the years, a number of efforts at different institutions have led to the creation and curation of databases to house genetic toxicology data, largely, with the aim of providing public access to facilitate research and regulatory assessments. This article provides a brief introduction to a new genetic toxicology portal called Mutation Analysis Informatics Tools (MutAIT) (www.mutait.org) that provides easy access to two of the largest genetic toxicology databases, the Mammalian Gene Mutation Database (MGMD) and TransgenicDB. TransgenicDB is a comprehensive collection of transgenic rodent mutation data initially compiled and collated by Health Canada. The updated MGMD contains approximately 50 000 individual mutation spectral records from the published literature. The portal not only gives access to an enormous quantity of genetic toxicology data, but also provides statistical tools for dose-response analysis and calculation of benchmark dose. Two important R packages for dose-response analysis are provided as web-distributed applications with user-friendly graphical interfaces. The 'drsmooth' package performs dose-response shape analysis and determines various points of departure (PoD) metrics and the 'PROAST' package provides algorithms for dose-response modelling. The MutAIT statistical tools, which are currently being enhanced, provide users with an efficient and comprehensive platform to conduct quantitative dose-response analyses and determine PoD values that can then be used to calculate human exposure limits or margins of exposure. PMID:26208916

  10. Effect of oleic acid on the allergenic properties of peanut and cashew allergens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oleic acid is the major fatty acid in peanuts and cashews. There is limited information about its effect on peanut and cashew allergens during heating. The objective was to determine if heat treatment with oleic acid changes the allergenic properties of these nut proteins. Peanut and cashew protein...

  11. The Role of Allergen Exposure and Avoidance in Asthma

    PubMed Central

    Baxi, Sachin N.; Phipatanakul, Wanda

    2010-01-01

    Allergy testing and avoidance of allergens plays an important role in asthma control. Increased allergen exposure, in genetically susceptible individuals, can lead to allergic sensitization. Continued allergen exposure can increase the risk of asthma and other allergic diseases. In a patient with persistent asthma, identification of indoor and outdoor allergens and subsequent avoidance can improve symptoms. Often times, a patient will have multiple allergies and the avoidance plan should target all positive allergens. Several studies have shown that successful allergen remediation includes a comprehensive approach including education, cleaning, physical barriers and maintaining these practices. PMID:20568555

  12. Is high pressure treatment able to modify the allergenicity of the largemouth bass allergens?

    NASA Astrophysics Data System (ADS)

    Liu, Chu-Yi; Tao, Sha; Liu, Rong; Chen, Fu-Sheng; Xue, Wen-Tong

    2012-12-01

    The aim of this paper is to study the influence of high pressure treatment on the structural changes and allergenicity of largemouth bass. We treated the allergens at 100, 200, 300 and 400 MPa for 15 min and at 300 MPa for 5, 10, 15, 20 and 30 min at 20 °C. The treated samples from largemouth bass were tested for their IgE-binding properties by combining Sodium dodecyl sulfate-Polyacrylamide gel electrophoresis (SDS-PAGE) with western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Circular dichroism analysis was performed to characterize the structural change. In summary, we can determine that the greatest structure changes were found for samples treated by 400 MPa for 15 min. High pressure treatment did change the structure, subunit composition and molecular weight of largemouth bass allergens, but it did not change the allergenicity of the allergens.

  13. Oral mucosal immunotherapy for allergic rhinitis: A pilot study

    PubMed Central

    Suurna, Maria V.; Rochlin, Kate; Bremberg, Maria G.; Tropper, Guy

    2016-01-01

    Background: The sublingual mucosa has been used for many years to apply allergenic extracts for the purpose of specific immunotherapy (IT). Although sublingual IT (SLIT) is both safe and efficacious, the density of antigen-presenting cells is higher in other regions of the oral cavity and vestibule, which make them a potentially desirable target for IT. Objective: To present the concept of oral mucosal IT (OMIT) and to provide pilot data for this extended application of SLIT. Methods: An open-label, 12-month, prospective study was undertaken as a preliminary step before a full-scale clinical investigation. Twenty-four individuals with allergic rhinitis received IT by applying allergenic extracts daily to either the oral vestibule plus oral cavity mucosa by using a glycerin-based toothpaste or to the sublingual mucosa by using 50% glycerin liquid drops. Adverse events, adherence rates, total combined scores, rhinoconjunctivitis quality-of-life questionnaire scores, changes in skin reactivity, and changes in serum antibody levels were measured for each participant. Results: No severe adverse events occurred in either group. The adherence rate was 80% for the OMIT group and 62% for the SLIT group (p = 0.61). Decreased total combined scores were demonstrated for both the OMIT group (15.6%) and the SLIT group (22.3%), although this decrease did not reach statistical significance in either group. Both groups achieved a meaningful clinical improvement of at least 0.5 points on rhinoconjunctivitis quality-of-life questionnaire. A statistically significant rise in specific immunoglobulin G4 (IgG4) was seen in both groups over the first 6 months of treatment. Conclusion: OMIT and SLIT demonstrated similar safety profiles and adherence rates. Measurements of clinical efficacy improved for both groups, but only changes in IgG4 achieved statistical significance. These pilot data provide enough evidence to proceed with a full-scale investigation to explore the role of OMIT in

  14. Induction of a Th1 immune response and suppression of IgE via immunotherapy with a recombinant hybrid molecule encapsulated in liposome-protamine-DNA nanoparticles in a model of experimental allergy.

    PubMed

    Nouri, Hamid Reza; Varasteh, Abdolreza; Jaafari, Mahmoud Reza; Davies, Janet M; Sankian, Mojtaba

    2015-07-01

    Liposome-protamine-DNA nanoparticles (LPD) are safe, effective, and non-toxic adjuvants that induce Th1-like immune responses. We hypothesized that encapsulation of allergens into liposomes could be an appropriate option for immunotherapy. The present study evaluated the immunotherapeutic potential of a recombinant hybrid molecule (rHM) encapsulated in LPD nanoparticles in a murine model of Chenopodium album allergy. BALB/c mice were sensitized with the allergen in alum, and the immunotherapy procedure was performed by subcutaneous injections of LPD-rHM, rHM, or empty LPD at weekly intervals. Sensitized mice developed a Th2-biased immune response characterized by strong specific IgG1 and IgE production, IL-4, and the transcription factor GATA3 in spleen cell cultures. Treatment with the LPD-rHM resulted in a reduction in IgE and a marked increase in IgG2a. The LPD-rHM induced allergen-specific responses with relatively high interferon-gamma production, as well as expression of the transcription factor T-bet in stimulated splenocytes. In addition, lymphoproliferative responses were higher in the LPD-rHM-treated mice than in the other groups. Removal of the nanoparticles from the rHM resulted in a decrease in the allergen's immunogenicity. These results indicate that the rHM complexed with LPD nanoparticles has a marked suppressive effect on the allergic response and caused a shift toward a Th1 pathway. PMID:25957889

  15. Allergens of the entomopathogenic fungus Beauveria bassiana

    PubMed Central

    Westwood, Greg S; Huang, Shih-Wen; Keyhani, Nemat O

    2005-01-01

    Background Beauveria bassiana is an important entomopathogenic fungus currently under development as a bio-control agent for a variety of insect pests. Although reported to be non-toxic to vertebrates, the potential allergenicity of Beauveria species has not been widely studied. Methods IgE-reactivity studies were performed using sera from patients displaying mould hypersensitivity by immunoblot and immunoblot inhibition. Skin reactivity to B. bassiana extracts was measured using intradermal skin testing. Results Immunoblots of fungal extracts with pooled as well as individual sera showed a distribution of IgE reactive proteins present in B. bassiana crude extracts. Proteinase K digestion of extracts resulted in loss of IgE reactive epitopes, whereas EndoH and PNGaseF (glycosidase) treatments resulted in minor changes in IgE reactive banding patterns as determined by Western blots. Immunoblot inhibitions experiments showed complete loss of IgE-binding using self protein, and partial inhibition using extracts from common allergenic fungi including; Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, Candida albicans, Epicoccum purpurascens, and Penicillium notatum. Several proteins including a strongly reactive band with an approximate molecular mass of 35 kDa was uninhibited by any of the tested extracts, and may represent B. bassiana specific allergens. Intradermal skin testing confirmed the in vitro results, demonstrating allergenic reactions in a number of individuals, including those who have had occupational exposure to B. bassiana. Conclusions Beauveria bassiana possesses numerous IgE reactive proteins, some of which are cross-reactive among allergens from other fungi. A strongly reactive potential B. bassiana specific allergen (35 kDa) was identified. Intradermal skin testing confirmed the allergenic potential of B. bassiana. PMID:15644142

  16. Expression, purification, and characterization of almond (Prunus dulcis) allergen Pru du 4

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biochemical characterizations of food allergens are required for understanding the allergenicity of food allergens. Such studies require a relatively large amount of highly purified allergens. Profilins from numerous species are known to be allergens, including food allergens, such as almond (Prunus...

  17. Melanoma immunotherapy dominates the field.

    PubMed

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  18. Novel immunotherapies for hematologic malignancies.

    PubMed

    Nelson, Michelle H; Paulos, Chrystal M

    2015-01-01

    The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise novel strategies that exploit the patient's immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematologic malignancies, including (i) conventional monoclonal therapies like rituximab; (ii) engineered monoclonal antibodies called bispecific T-cell engagers; (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4, and IDO); and (iv) adoptive cell transfer therapy with T cells engineered to express chimeric antigen receptors or T-cell receptors. We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

  19. Immunotherapy in Sarcoma: Future Horizons.

    PubMed

    Burgess, Melissa; Gorantla, Vikram; Weiss, Kurt; Tawbi, Hussein

    2015-11-01

    Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative regulatory signals from the innate immune system. Sarcomas are among the first tumors to be considered for immune interventions. From Coley's toxin to cytokine-based therapies to adoptive cell therapy, there have been numerous immunotherapeutic investigations in this patient population. A promising strategy includes adoptive T cell therapy which has been studied in small cohorts of synovial sarcoma, a subtype that is known to widely express the cancer testis antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal cell carcinoma demonstrate the utility and tremendous efficacy of immune checkpoint blockade with increased rates of durable responses compared to standard therapies. Responses in traditionally "non-immunogenic" tumors, such as lung and bladder cancers, provide ample rationale for the study of immune checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses in sarcomas, further research will help clarify optimal patient selection for future clinical trials and new combinatorial immunotherapeutic strategies. PMID:26423769

  20. Immunotherapy in renal cell carcinoma.

    PubMed

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  1. Melanoma immunotherapy dominates the field

    PubMed Central

    Diamantopoulos, Panagiotis

    2016-01-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  2. Immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G

    2005-09-01

    Immunotherapeutic strategies have become part of standard cancer treatment. Chimeric and humanized antibodies have demonstrated activity against a variety of tumors. Although the humanized anti-CD33 antibody HuM195 has only modest activity against overt acute myeloid leukemia (AML), it can eliminate minimal residual disease in acute promyelocytic leukemia. High-dose radioimmunotherapy with b-particle-emitting isotopes targeting CD33, CD45, and CD66 can potentially allow intensification of antileukemic therapy before hematopoietic stem cell transplantation. Conversely, a-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumor cell kill while sparing surrounding normal tissues. Targeted chemotherapy with the anti-CD33- calicheamicin construct gemtuzumab ozogamicin has produced remissions in relapsed AML and appears promising when used in combination with standard chemotherapy for newly diagnosed AML. T-cell recognition of peptide antigens presented on the cell surface in combination with major histocompatibility complex antigen provides another potentially promising approach for the treatment of AML. PMID:16091194

  3. Induction of Bronchial Tolerance After 1 Cycle of Monophosphoryl-A-Adjuvanted Specific Immunotherapy in Children With Grass Pollen Allergies

    PubMed Central

    Girod, Katharina; Zielen, Stefan; Schubert, Ralf; Schulze, Johannes

    2016-01-01

    Purpose Subcutaneous allergen-specific immunotherapy (SCIT) is a well-established and clinically effective method to treat allergic diseases, such as rhinitis and asthma. It remains unclear how soon after initiation of an ultra-short course of grass pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL)-specific bronchial tolerance can be induced. Methods In a prospective study of 69 children double-sensitized to birch and grass pollens (51 males, average age 11.1 years), development of bronchial tolerance after 1 cycle of SCIT for grass was evaluated. In all the patients, the bronchial allergen provocation test (BAP) was performed before and after treatment. According to the results of the first BAP, the patients were divided into 2 groups: those showing a negative BAP with a decrease in FEV1 of <20% (seasonal allergic rhinitis [SAR] group, n=47); and those showing a positive BAP with a decrease in FEV1 of ≥20% (SAR with allergic asthma [SAR and Asthma] group, n=22). All the patients received MPL-adjuvanted, ultra-short course immunotherapy for birch, but only those with a positive BAP to grass received MPL-SCIT for grass. Results After the pollen season, the BAP in the SAR group remained unchanged, while it was improved in the SAR and Asthma group (decrease in FEV1 of 28.8% vs 12.5%, P<0.01). The IgG4 levels increased after SCIT (median before SCIT 0.34 to 11.4 after SCIT), whereas the total and specific IgE levels remained unchanged. Conclusions After 1 cycle of MPL-SCIT, specific bronchial tolerance may be significantly induced, whereas in patients without SCIT, bronchial hyperactivity may remain unchanged. PMID:26922936

  4. Nasal challenge with ragweed pollen in hay fever patients. Effect of immunotherapy.

    PubMed Central

    Creticos, P S; Adkinson, N F; Kagey-Sobotka, A; Proud, D; Meier, H L; Naclerio, R M; Lichtenstein, L M; Norman, P S

    1985-01-01

    Challenge of the nasal mucosa of allergic subjects with specific allergen induces not only the expected sneezing and rhinorrhea, but also the appearance in nasal secretions of mediators commonly associated with activation of mast cells or basophils: histamine, leukotrienes, prostaglandin D2 (PGD2), kinins, and TAME ([3H]-N-alpha-tosyl-L-arginine methyl ester)-esterase. To determine whether specific immunotherapy alters mediator release in vivo, nasal pollen challenge was used to compare 27 untreated highly sensitive ragweed (RW)-allergic subjects with 12 similarly sensitive patients receiving long-term immunotherapy (3-5 yr) with RW extract (median dose, 6 micrograms RW antigen E). The two groups were equally sensitive based on skin tests and basophil histamine release. The immunized group had a diminished response as demonstrated by (a) the treated group required higher pollen doses to excite sneezing or mediator release; (b) significantly fewer subjects in the treated group released mediators at any dose (TAME-esterase [P = 0.005], PGD2 [P = 0.04]), and (c) the treated group released 3-5-fold less mediator (TAME-esterase [P = 0.01], and histamine [P = 0.02]). PMID:2416777

  5. Evaluation of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy.

    PubMed

    Harmanci, Koray; Razi, Cem H; Toyran, Muge; Kanmaz, Gozde; Cengizlier, Mehmet R

    2010-03-01

    Specific immunotherapy (SIT) is one of the treatment modalities recomended for the management of asthma and allergic rhinitis by international guidelines. A potential benefit of immunotherapy (IT) is to prevent the development of sensitisation to new allergens. There is stil no conclusion on this subject. One hundred twenty-two children 8-18 years old with intermittent asthma, with or without allergic rhinitis, all of whom were monosensitised to house dust mite (HDM) were selected. Sixty two of these children accepted to receive SIT with HDM extract for 4 years and the remaining 60 did not accept SIT and were treated with asthma medications only. This second group of children served as the control group. At the end of the 4-year study period, 36 of the 53 patients (67.9%) in the SIT group showed no new sensitizations, compared to 38 of 52 (73.0%) in the control group (p = 0.141). The most frequent new sensitizations at the end of the study were pollens, grasses and olive polen, followed by animal dander, alternaria and cockroach. In conclusion, SIT may not prevent the onset of new sensitizations in asthmatic children monosensitized to house dust mites. Further investigation is required to clarify the immunologic mechanisms and other factors by which SIT reduces or not the development of new sensitizations in monosensitized children. PMID:20527510

  6. Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice.

    PubMed

    Maaske, A; Devos, F C; Niezold, T; Lapuente, D; Tannapfel, A; Vanoirbeek, J A; Überla, K; Peters, M; Tenbusch, M

    2016-09-10

    Considering the rising incidence of allergic asthma, the symptomatic treatments that are currently applied in most cases are less than ideal. Specific immunotherapy is currently the only treatment that is able to change the course of the disease, but suffers from a long treatment duration. A gene based immunization that elicits the targeting of allergens towards dendritic cells in a steady-state environment might have the potential to amend these difficulties. Here we used a replication deficient adenovirus to induce the mucosal expression of OVA coupled to a single-chain antibody against DEC-205. A single intranasal vaccination was sufficient to mitigate an OVA-dependent asthmatic phenotype in a murine model. Invasive airway measurements demonstrated improved lung function after Ad-Dec-OVA treatment, which was in line with a marked reduction of goblet cell hyperplasia and lung eosinophilia. Furthermore OVA-specific IgE titers and production of type 2 cytokines were significantly reduced. Together, the here presented data demonstrate the feasibility of mucosal expression of DEC-targeted allergens as a treatment of allergic asthma. PMID:27374625

  7. Novel strategy to create hypoallergenic peanut protein-polyphenol edible matrices for oral immunotherapy.

    PubMed

    Plundrich, Nathalie J; Kulis, Mike; White, Brittany L; Grace, Mary H; Guo, Rishu; Burks, A Wesley; Davis, Jack P; Lila, Mary Ann

    2014-07-23

    Peanut allergy is an IgE-mediated hypersensitivity. Upon peanut consumption by an allergic individual, epitopes on peanut proteins bind and cross-link peanut-specific IgE on mast cell and basophil surfaces triggering the cells to release inflammatory mediators responsible for allergic reactions. Polyphenolic phytochemicals have high affinity to bind proteins and form soluble and insoluble complexes with unique functionality. This study investigated the allergenicity of polyphenol-fortified peanut matrices prepared by complexing various polyphenol-rich plant juices and extracts with peanut flour. Polyphenol-fortified peanut matrices reduced IgE binding to one or more peanut allergens (Ara h 1, Ara h 2, Ara h 3, and Ara h 6). Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) suggested changes in secondary protein structure. Peanut protein-cranberry polyphenol fortified matrices triggered significantly less basophil degranulation than unmodified flour in an ex vivo assay using human blood and less mast cell degranulation when used to orally challenge peanut-allergic mice. Polyphenol fortification of peanut flour resulted in a hypoallergenic matrix with reduced IgE binding and degranulation capacity, likely due to changes in protein secondary structure or masking of epitopes, suggesting potential applications for oral immunotherapy. PMID:24758688

  8. Advances in the understanding of cancer immunotherapy.

    PubMed

    Shore, Neal D

    2015-09-01

    The principal role of the immune system is to prevent and eradicate pathogens and infections. The key characteristics or features of an effective immune response include specificity, trafficking, antigen spread and durability (memory). The immune system is recognised to have a critical role in controlling cancer through a dynamic relationship with tumour cells. Normally, at the early stages of tumour development, the immune system is capable of eliminating tumour cells or keeping tumour growth abated; however, tumour cells may evolve multiple pathways over time to evade immune control. Immunotherapy may be viewed as a treatment designed to boost or restore the ability of the immune system to fight cancer, infections and other diseases. Immunotherapy manifests differently from traditional cancer treatments, eliciting delayed response kinetics and thus may be more effective in patients with lower tumour burden, in whom disease progression may be less rapid, thereby allowing ample time for the immunotherapy to evolve. Because immunotherapies may have a different mechanism of action from traditional cytotoxic or targeted biological agents, immunotherapy techniques have the potential to combine synergistically with traditional therapies. PMID:24612369

  9. Current Studies of Immunotherapy on Glioblastoma.

    PubMed

    Agrawal, Neena Stephanie; Miller, Rickey; Lal, Richa; Mahanti, Harshini; Dixon-Mah, Yaenette N; DeCandio, Michele L; Vandergrift, W Alex; Varma, Abhay K; Patel, Sunil J; Banik, Naren L; Lindhorst, Scott M; Giglio, Pierre; Das, Arabinda

    2014-04-01

    Glioblastoma is a form of brain tumor with a very high morbidity and mortality. Despite decades of research, the best treatments currently in clinical practice only extend survival by a number of months. A promising alternative to conventional treatment for glioblastomas is immunotherapy. Although proposed over a century ago, the field of cancer immunotherapy has historically struggled to translate it into effective clinical treatments. Better understanding is needed of the various regulatory and co-stimulatory factors in the glioblastoma patient for more efficient immunotherapy treatments. The tumor microenvironment is anatomically shielded from normal immune-surveillance by the blood-brain barrier, irregular lymphatic drainage system, and it's in a potently immunosuppressive environment. Immunotherapy can potentially manipulate these forces effectively to enhance anti-tumor immune response and clinical benefit. New treatments utilizing the immune system show promise in terms of targeting and efficacy. This review article attempts to discuss current practices in glioblastoma treatment, the theory behind immunotherapy, and current research into various clinical trials. PMID:25346943

  10. T-cell response to allergens.

    PubMed

    Ozdemir, Cevdet; Akdis, Mübeccel; Akdis, Cezmi A

    2010-01-01

    Anaphylaxis is a life-threatening IgE-dependent type 1 hypersensitivity reaction in which multiple organ systems are involved. The existence of allergen exposure and specific IgE are the major contributors to this systemic reaction. The decision of the immune system to respond to allergens is highly dependent on factors including the type and load of allergen, behavior and type of antigen-presenting cells, innate immune response stimulating substances in the same micromilieu, the tissue of exposure, interactions between T and B lymphocytes, costimulators, and genetic propensity known as atopy. Antigen-presenting cells introduce processed allergens to T-helper lymphocytes, where a decision of developing different types of T-cell immunity is given under the influence of several cytokines, chemokines, costimulatory signals and regulatory T cells. Among Th2-type cytokines, interleukin (IL)-4 and IL-13 are responsible for class switching in B cells, which results in production of allergen-specific IgE antibodies that bind to specific receptors on mast cells and basophils. After re-exposure to the sensitized allergen, this phase is followed by activation of IgE Fc receptors on mast cells and basophils resulting in biogenic mediator releases responsible for the symptoms and signs of anaphylaxis. Since the discovery of regulatory T cells, the concepts of immune regulation have substantially changed during the last decade. Peripheral T-cell tolerance is a key immunologic mechanism in healthy immune response to self antigens and non-infectious non-self antigens. Both naturally occurring CD4+CD25+ regulatory T (Treg) cells and inducible populations of allergen-specific, IL-10-secreting Treg type 1 cells inhibit allergen-specific effector cells and have been shown to play a central role in the maintenance of peripheral homeostasis and the establishment of controlled immune responses. On the other hand, Th17 cells are characterized by their IL-17 (or IL-17A), IL-17F, IL-6

  11. Reduction and alkylation of peanut allergen isoforms Ara h 2 and Ara h 6; characterization of intermediate- and end products.

    PubMed

    Apostolovic, Danijela; Luykx, Dion; Warmenhoven, Hans; Verbart, Dennis; Stanic-Vucinic, Dragana; de Jong, Govardus A H; Velickovic, Tanja Cirkovic; Koppelman, Stef J

    2013-12-01

    Conglutins, the major peanut allergens, Ara h 2 and Ara h 6, are highly structured proteins stabilized by multiple disulfide bridges and are stable towards heat-denaturation and digestion. We sought a way to reduce their potent allergenicity in view of the development of immunotherapy for peanut allergy. Isoforms of conglutin were purified, reduced with dithiothreitol and subsequently alkylated with iodoacetamide. The effect of this modification was assessed on protein folding and IgE-binding. We found that all disulfide bridges were reduced and alkylated. As a result, the secondary structure lost α-helix and gained some β-structure content, and the tertiary structure stability was reduced. On a functional level, the modification led to a strongly decreased IgE-binding. Using conditions for limited reduction and alkylation, partially reduced and alkylated proteins were found with rearranged disulfide bridges and, in some cases, intermolecular cross-links were found. Peptide mass finger printing was applied to control progress of the modification reaction and to map novel disulfide bonds. There was no preference for the order in which disulfides were reduced, and disulfide rearrangement occurred in a non-specific way. Only minor differences in kinetics of reduction and alkylation were found between the different conglutin isoforms. We conclude that the peanut conglutins Ara h 2 and Ara h 6 can be chemically modified by reduction and alkylation, such that they substantially unfold and that their allergenic potency decreases. PMID:24145103

  12. 78 FR 66011 - Allergenic Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ..., perennial rye, Timothy, and Kentucky bluegrass mixed pollens allergen extract tablet for sublingual use... recommendations on the safety and efficacy of Grastek, a Timothy grass pollen allergen extract tablet...

  13. Pollensomes as Natural Vehicles for Pollen Allergens.

    PubMed

    Prado, Noela; De Linares, Concepción; Sanz, María L; Gamboa, Pedro; Villalba, Mayte; Rodríguez, Rosalía; Batanero, Eva

    2015-07-15

    Olive (Olea europaea) pollen constitutes one of the most important allergen sources in the Mediterranean countries and some areas of the United States, South Africa, and Australia. Recently, we provided evidence that olive pollen releases nanovesicles of respirable size, named generically pollensomes, during in vitro germination. Olive pollensomes contain allergens, such as Ole e 1, Ole e 11, and Ole e 12, suggesting a possible role in allergy. The aim of this study was to assess the contribution of pollensomes to the allergic reaction. We show that pollensomes exhibit allergenic activity in terms of patients' IgE-binding capacity, human basophil activation, and positive skin reaction in sensitized patients. Furthermore, allergen-containing pollensomes have been isolated from three clinically relevant nonphylogenetically related species: birch (Betula verrucosa), pine (Pinus sylvestris), and ryegrass (Lolium perenne). Most interesting, pollensomes were isolated from aerobiological samples collected with an eight-stage cascade impactor collector, indicating that pollensomes secretion is a naturally occurring phenomenon. Our findings indicate that pollensomes may represent widespread vehicles for pollen allergens, with potential implications in the allergic reaction. PMID:26041541

  14. Congruence between international guidelines and mite specific immunotherapy prescribing practices.

    PubMed

    Antonicelli, L; Braschi, M C; Bilò, M B; Angino, A; Pala, A P; Baldacci, S; Maio, S; Bonifazi, F

    2011-10-01

    Both rhinitis (ARIA) and asthma (GINA) guidelines recommend allergen-specific immunotherapy (SIT) tailored to the specific levels of severity of each disease. Real world studies evaluating congruence between these recommendations and prescribing practice in the single patient with comorbidity are lacking. An observational polycentric study was carried out in 518 patients recruited from 34 allergy centers throughout Italy. A questionnaire was administered to each consecutive patient over a span of four months. Taking into account guideline recommendations for both diseases, concomitant in the same patient, three subsets resulted: patients not eligible for SIT (11%); patients eligible for SIT for one disease only (60%); patients eligible for SIT for both diseases (29%). SIT was prescribed in 257 (49.6%) subjects. The level of SIT prescription was about 50% in all three groups. Consistent with the ARIA guidelines, a correlation between the prescription of SIT and the severity of rhinitis was documented (r=0.87; p=0.001). An association with asthma severity was found (p=0.02), but the trend was inconsistent with the GINA recommendations. Young age was the most important factor for SIT prescription both in the eligible for one disease and in the eligible for both diseases subset. The tendency towards worsening of symptoms was a factor for SIT in the eligible for one disease subset. In mite allergic patients with rhinitis and asthma comorbidity, the severity of rhinitis and the young age are the most important factors driving the SIT prescription. The congruence of SIT prescription was better for the ARIA than GINA guidelines. PMID:21628094

  15. An adjuvant free mouse model of oral allergenic sensitization to rice seeds protein

    PubMed Central

    2011-01-01

    Background Rice is commonly known as a staple crop consumed worldwide, though with several rice proteins being reported for allergic properties in clinical studies. Thus, there is a growing need for the development of an animal model to better understand the allergenicity of rice proteins and the immunological and pathophysiological mechanisms underlying the development of food allergy. Methods Groups of BALB/c mice were sensitized daily with freshly homogenized rice flour (30 mg or 80 mg) without adjuvant by intragastric gavage. In addition, the mice were challenged with extracted rice flour proteins at several time points intragastrically. Hypersensitivity symptoms in mice were evaluated according to a scoring system. Vascular leakage, ELISA of rice protein-specific IgE, histopathology of small intestine, and passive cutaneous anaphylaxis were conducted on challenged mice. Results An adjuvant free mouse model of rice allergy was established with sensitized mice showing increased scratching behaviors and increased vascular permeability. Rice protein-specific IgE was detected after eighteen days of sensitization and from the fifth challenge onwards. Inflammatory damage to the epithelium in the small intestine of mice was observed beyond one month of sensitization. Passive cutaneous anaphylaxis results confirmed the positive rice allergy in the mouse model. Conclusions We introduced a BALB/c mouse model of rice allergy with simple oral sensitization without the use of adjuvant. This model would serve as a useful tool for further analysis on the immunopathogenic mechanisms of the various rice allergens, for the evaluation of the hypersensitivity of rice or other cereal grains, and to serve as a platform for the development of immunotherapies against rice allergens. PMID:21605393

  16. Indoor determinants of dustborne allergens in Mexican homes

    PubMed Central

    Hernández-Cadena, Leticia; Zeldin, Darryl C.; Sever, Michelle L.; Sly, Peter D.; London, Stephanie J.; Escamilla-Nuñez, María Consuelo; Romieu, Isabelle

    2015-01-01

    Exposure to indoor allergens represents a significant risk factor for allergies and asthma in several parts of the world. In Mexico, few studies have evaluated indoor allergens, including cat, dog, and mouse allergens and the factors that predict their presence. This study evaluates the main environmental and household predictors of high prenatal allergen levels and multiple allergen exposures in a birth cohort from Mexico City. A cross-sectional study was conducted as part of a birth cohort study of 1094 infants recruited during pregnancy and followed until delivery. We collected dust samples in a subset of 264 homes and assessed environmental factors. Der p 1, Der f 1, dust mite group 2, Fel d 1, Can f 1, Rat n 1, Mus m 1, and Bla g 2 concentrations in dust samples were measured using immunoassays. To define detectable allergen levels, the lowest limits of detection for each allergen were taken as cutoff points. Overall allergen exposure was considered high when four or more allergens exceeded detectable levels in the same household. Logistic regression was used for predictive models. Eighty-five percent of homes had at least one allergen in dust over the detection limit, 52.1% had high exposure (four or more allergens above detectable limits), and 11.7% of homes had detectable levels for more than eight allergens. Der p 1, Der p 2, Mus m 1, and Fel d 1 were the most frequent allergens detected. Each allergen had both common and distinct predictors. The main predictors of a high multiple allergen index were the size of the home, pesticide use, mother's age, mother as homemaker, and season. Increased indoor environmental allergen exposure is mainly related to sociodemographic factors and household cleaning. PMID:25715241

  17. Indoor allergens in Minnesota schools and child care centers.

    PubMed

    Tranter, Daniel C; Wobbema, Amanda Teresa; Norlien, Kathleen; Dorschner, Dale F

    2009-09-01

    Elevated concentrations of allergens in the indoor environment may cause allergic sensitization and symptoms. Occupant exposure to indoor allergens in educational facilities should and can be controlled. This study (1) assessed the presence of indoor allergens in Minnesota schools and child care centers, (2) characterized the distribution of allergens in different materials, and (3) evaluated the effect of building and maintenance interventions on allergen concentrations. Settled dust samples were collected from carpet, vinyl tile floors, and upholstered furniture in six schools and seven child care centers before and after interventions. Interventions included changes to cleaning, ventilation, entry mats, furnishings, flooring, and classroom items. The amount of total dust, culturable fungi, and indoor allergens--cockroach, dust mite, cat, and dog--were quantified in the dust samples. Cockroach and dust mite allergens were generally low and below the detection limit, but one dust mite allergen was detected in some areas. Cat and dog allergens were frequently detected at elevated levels, with half the samples above the provisional sensitization risk thresholds and a few samples above the symptom thresholds. Allergen concentrations were highest in upholstered furniture, followed by carpeting and then vinyl floor tile. Cat and dog allergens were lower after the interventions. Cat and dog allergens, but not dust mite and cockroach allergens, seem to be ubiquitous in child care and elementary schools of the U.S. Midwest. These allergens may contribute to sensitization in atopic individuals and occasionally cause symptoms in sensitized allergic individuals. Fleecy materials that are not adequately cleaned, such as upholstered furniture, appear to be the most significant allergen reservoirs. Modest environmental interventions can be implemented by building staff, which should result in lower allergen concentrations. PMID:19585331

  18. Indoor determinants of dustborne allergens in Mexican homes.

    PubMed

    Hernández-Cadena, Leticia; Zeldin, Darryl C; Barraza-Villarreal, Albino; Sever, Michelle L; Sly, Peter D; London, Stephanie J; Escamilla-Nuñez, María Consuelo; Romieu, Isabelle

    2015-01-01

    Exposure to indoor allergens represents a significant risk factor for allergies and asthma in several parts of the world. In Mexico, few studies have evaluated indoor allergens, including cat, dog, and mouse allergens and the factors that predict their presence. This study evaluates the main environmental and household predictors of high prenatal allergen levels and multiple allergen exposures in a birth cohort from Mexico City. A cross-sectional study was conducted as part of a birth cohort study of 1094 infants recruited during pregnancy and followed until delivery. We collected dust samples in a subset of 264 homes and assessed environmental factors. Der p 1, Der f 1, dust mite group 2, Fel d 1, Can f 1, Rat n 1, Mus m 1, and Bla g 2 concentrations in dust samples were measured using immunoassays. To define detectable allergen levels, the lowest limits of detection for each allergen were taken as cutoff points. Overall allergen exposure was considered high when four or more allergens exceeded detectable levels in the same household. Logistic regression was used for predictive models. Eighty-five percent of homes had at least one allergen in dust over the detection limit, 52.1% had high exposure (four or more allergens above detectable limits), and 11.7% of homes had detectable levels for more than eight allergens. Der p 1, Der p 2, Mus m 1, and Fel d 1 were the most frequent allergens detected. Each allergen had both common and distinct predictors. The main predictors of a high multiple allergen index were the size of the home, pesticide use, mother's age, mother as homemaker, and season. Increased indoor environmental allergen exposure is mainly related to sociodemographic factors and household cleaning. PMID:25715241

  19. Efficacies of immunotherapy with polypeptide vaccine from ProDer f 1 in asthmatic mice

    PubMed Central

    Li, Chaopin; Li, Qiuyu; Jiang, Yuxin

    2015-01-01

    Allergic asthma is associated with the major house dust mite group 1 allergens Der p 1 and Der f 1, which belongs to the papin-like protease family and is the most potent of indoor allergens and allergen-specific immunotherapy (SIT), is seen as effective intervention for the entity. The current study was designed to verify the SIT efficacies of the enzymatic hydrolysates (papain and trypsin) in mice with asthma. We initially developed the asthmatic mouse models with ProDer f 1, and respectively applied recombinant ProDer f 1 protein and the two kinds of enzymatic hydrolysates for SIT. The results were verified by measuring the contents of IL-4, IL-10, IL-17 and IFN-γ changed in both bronchoalveolar lavage fluid (BALF) and supernatant of splenocyte culture as well as level changes of specific IgE and IgG2a in the serum. After SIT intervention, the symptoms of allergic inflammation was alleviated significantly in mice treated with ProDer f 1 protein and the two enzymatic hydrolysates via detection of the lung tissue sections, and infiltration of inflammatory cells was also notably depressed as compared with the models, though the epithelial structure in airways remained similar with the PBS group. In addition, we observed lower serum contents of the specific IgE antibody and lower levels of IL-4, IL-17 in BALF and splenic cells in mice undergone SIT, whereas specific IgG2a, IFN-γ and IL-10 in BALF and supernatant of splenocyte culture were higher as compared to the asthma group. The findings suggest the SIT using the above two kinds of hydrolysates may effectively inhibit the allergic inflammation in the airways of mouse models sensitized with ProDer f 1 protein. PMID:25932130

  20. Increased allergen-specific Th2 responses in vitro in atopic subjects receiving subclinical allergen challenge.

    PubMed

    Gabrielsson, S; Paulie, S; Roquet, A; Ihre, E; Lagging, E; van Hage-Hamsten, M; Härfast, B; Troye-Blomberg, M

    1997-08-01

    The study aimed to determine whether inhalation of subclinical allergen doses-leads to a shift in the balance between T helper (Th) 1 and Th2 cells in asthmatic patients. Elevated IgE requires allergen-specific T cells producing cytokines such as interleukin (IL)-4 or IL-13. Interferon-gamma (IFN-gamma) produced by Th1 cells counteracts the effects of IL-4. In nature, allergic persons are often exposed to low levels of allergen, leading to hyperreactivity, but not to acute allergic reactions. In this study, nine allergic persons inhaled low doses of allergen or placebo in a double-blind manner over seven consecutive weekdays. During the study, the bronchial responsiveness to histamine challenge increased, but no subject exhibited asthmatic symptoms. Blood was drawn on days 0, 1, 4, and 9, and the number of IL-4- and IFN-gamma-producing cells was measured by enzyme-linked immunospot (ELISPOT) assay after in vitro stimulation with a low-dose phytohemagglutinin (PHA) mixed with the relevant allergen or with PHA alone. In three of the four subjects receiving allergen, the IL-4/IFN-gamma ratio increased during the time of the study. No increase was seen in the placebo group. No increase was seen in serum IgE levels in any of the groups. We conclude that a shift in the balance between Th1 and Th2 cells can be detected in subjects exposed to subclinical allergen doses. PMID:9284986

  1. What Is Recent in Pancreatic Cancer Immunotherapy?

    PubMed Central

    Niccolai, Elena; Prisco, Domenico; D'Elios, Mario Milco; Amedei, Amedeo

    2013-01-01

    Pancreatic cancer (PC) represents an unresolved therapeutic challenge, due to the poor prognosis and the reduced response to currently available treatments. Pancreatic cancer is the most lethal type of digestive cancers, with a median survival of 4–6 months. Only a small proportion of PC patients is curative by surgical resection, whilst standard chemotherapy for patients in advanced disease generates only modest effects with considerable toxic damages. Thus, new therapeutic approaches, specially specific treatments such as immunotherapy, are needed. In this paper we analyze recent preclinical and clinical efforts towards immunotherapy of pancreatic cancer, including passive and active immunotherapy approaches, designed to target pancreatic-cancer-associated antigens and to elicit an antitumor response in vivo. PMID:23509731

  2. Immunotherapy advances in uro-genital malignancies.

    PubMed

    Ratta, Raffaele; Zappasodi, Roberta; Raggi, Daniele; Grassi, Paolo; Verzoni, Elena; Necchi, Andrea; Di Nicola, Massimo; Salvioni, Roberto; de Braud, Filippo; Procopio, Giuseppe

    2016-09-01

    Immunotherapy for the treatment of cancer has made significant progresses over the last 20 years. Multiple efforts have been attempted to restore immune-mediated tumor elimination, leading to the development of several targeted immunotherapies. Data from recent clinical trials suggest that these agents might improve the prognosis of patients with advanced genito-urinary (GU) malignancies. Nivolumab has been the first immune checkpoint-inhibitor approved for pre-treated patients with metastatic renal cell carcinoma. Pembrolizumab and atezolizumab have shown promising results in both phase I and II trials in urothelial carcinoma. Brentuximab vedotin has demonstrated early signals of clinical activity and immunomodulatory effects in highly pre-treated patients with testicular germ cell tumors. In this review, we have summarized the major clinical achievements of immunotherapy in GU cancers, focusing on immune checkpoint blockade as well as the new immunomodulatory monoclonal antibodies (mAbs) under clinical evaluation for these malignancies. PMID:27372200

  3. Development of Novel Immunotherapies for Multiple Myeloma.

    PubMed

    Al-Hujaily, Ensaf M; Oldham, Robyn A A; Hari, Parameswaran; Medin, Jeffrey A

    2016-01-01

    Multiple myeloma (MM) is a disorder of terminally differentiated plasma cells characterized by clonal expansion in the bone marrow (BM). It is the second-most common hematologic malignancy. Despite significant advances in therapeutic strategies, MM remains a predominantly incurable disease emphasizing the need for the development of new treatment regimens. Immunotherapy is a promising treatment modality to circumvent challenges in the management of MM. Many novel immunotherapy strategies, such as adoptive cell therapy and monoclonal antibodies, are currently under investigation in clinical trials, with some already demonstrating a positive impact on patient survival. In this review, we will summarize the current standards of care and discuss major new approaches in immunotherapy for MM. PMID:27618026

  4. Humoral and cellular cross-reactivity between Amb a 1, the major ragweed pollen allergen, and its mugwort homolog Art v 6.

    PubMed

    Jahn-Schmid, Beatrice; Hauser, Michael; Wopfner, Nicole; Briza, Peter; Berger, Uwe E; Asero, Riccardo; Ebner, Christof; Ferreira, Fatima; Bohle, Barbara

    2012-02-01

    Ragweed and mugwort are closely related weeds that represent the major cause of pollen allergy in late summer. Concomitant sensitization and clinical cross-reactivity frequently occur in subjects who are coexposed to both pollen species, and have implications for diagnosis and specific immunotherapy. Molecules involved in this cross-reactivity might be Amb a 1, the major ragweed pollen allergen, and Art v 6, a highly homologous allergen from mugwort. Therefore, we investigated the IgE and T cell response to Art v 6 of 60 weed pollen-allergic patients and assessed its immunological cross-reactivity with Amb a 1. Results of ELISA inhibition experiments suggested that both allergens are largely cross-reactive, but Amb a 1 possesses more IgE epitopes than Art v 6. In patients with IgE to both allergens, Amb a 1-induced T cell lines and clones responded weakly to Art v 6. Moreover, Art v 6-induced T cell lines responded stronger to Amb a 1. T cell epitope mapping of Art v 6 revealed that it contains only a few cross-reactive epitopes, which is opposed to the multiple T cell-activating regions present in Amb a 1. In summary, Amb a 1 can elicit more diverse allergen-specific IgE and T cell responses than Art v 6 and dominates the cross-reactivity with its homolog. Nevertheless, Art v 6 can act as a primary sensitizing allergen in areas with high mugwort pollen exposure, and consequently may facilitate sensitization to Amb a 1 by epitope cross-recognition of T and B cells. PMID:22205029

  5. Engineering, purification and applications of His-tagged recombinant antibody fragments with specificity for the major birch pollen allergen, bet v1.

    PubMed

    Flicker, S; Laffer, S; Steinberger, P; Alhani, B; Zhu, Y; Laukkanen, M L; Keinänen, K; Kraft, D; Valenta, R

    2000-01-01

    Type I allergy, an immunodisorder affecting almost 20% of the population worldwide, is based on the production of IgE antibodies against per se harmless allergens. We report the expression of hexahistidine-tagged antibody fragments (Fabs) with specificity for Bet v1, the major birch pollen allergen, in Escherichia coli. The cDNA coding for the heavy chain fragment of a mouse monoclonal anti-Bet v1 antibody, Bip 1, was engineered by PCR to contain a hexahistidine-encoding 3' end. The modified Bip1 heavy chain cDNA was co-expressed in E. coli XL-1 Blue with the Bip 1 light chain cDNA using the combinatorial plasmid pComb3H. His-tagged recombinant (r) Bip 1 Fabs were isolated by nickel affinity chromatography and rBip 1 Fabs without His-tag were purified via affinity to rBet v1. rBip 1 Fabs with and without His-tag bound specifically to rBet v1 and, like Bet v1 -specific human serum IgE and rabbit-anti rBet v1 antibodies, cross-reacted with Bet v1-related allergens in other plant-species (alder, oak, hazelnut). We demonstrate the usefulness of His-tagged rBip 1 Fabs (1) for the identification of pollen samples containing Bet v 1 by particle blotting, (2) forthe detection of Bet v1-specific IgE antibodies in human serum samples by sandwich ELISA and (3) for the quantification of Bet v1 in solution. Based on these examples we suggest to use rBip 1 Fabs for the detection of Bet v1 and Bet v1-related allergens in natural allergen sources for allergy prevention, as well as for the standardization of natural allergen extracts produced for diagnosis and immunotherapy of birch pollen allergy. PMID:10722049

  6. Cardiac urticaria caused by eucleid allergen

    PubMed Central

    Zhan, Xiaodong; Li, Chaopin; Wu, Qianwen

    2015-01-01

    Urticaria is a common allergic diseases, which involve respiratory and digestive system being suffered in some population. Yet, relatively little research has been done on the adverse effect on the heart. We did this research to examine the correlation between the abnormality of ECG in the patients with acute allergic urticaria and the antigen of eucleid. The antigen (allergen of eucleid and other allergens) was used to test the patients with acute allergic urticaria by skin prick test and electrocardiogram was employed to examine the patients with strong positive (moth & caterpillar) eucleid antigen. Strong positive eucleid antigen was identified in 84 cases with abnormal electrocardiographic pattern of diversity. So, the acute allergic skin urticaria caused by eucleid allergen may impose strong effect on the heart and thus lead to allergic cardiac urticaria. PMID:26885121

  7. Profilins: mimickers of allergy or relevant allergens?

    PubMed

    Santos, Alexandra; Van Ree, Ronald

    2011-01-01

    Profilins are ubiquitous proteins, present in all eukaryotic cells and identified as allergens in pollen, latex and plant foods. The highly conserved structure justifies the cross-reactive nature of IgE antibodies against plant profilins and their designation as pan-allergens. Primary sensitization to profilin seems to arise from pollen sensitization with later development of cross-reactive IgE antibodies against plant food (and possibly latex) profilins. The role of profilin in inducing allergic symptoms needs to be evaluated and raises important issues in allergy diagnosis due to cross-reactivity. IgE cross-reactivity among profilins is associated with multiple pollen sensitization and with various pollen-food syndromes. In respiratory allergy, sensitization to pollen to which the patient has virtually no environmental exposure has been identified as a manifestation of profilin sensitization. As a food allergen, profilin usually elicits mild reactions, such as oral allergy syndrome, is not modified by processing and is especially important in allergy to some fruits, such as melon, watermelon, banana, tomato, citrus fruit and persimmon. Purified natural and recombinant profilins for in vitro and in vivo allergy tests are helpful in the diagnostic work-up. Herein we review the current state of knowledge about the allergen profilin and its implications in the diagnosis and treatment of allergic diseases. We conclude that, although its role in triggering allergic symptoms is still controversial, profilin is undoubtedly a relevant allergen. As a pan-allergen, profilin is associated with multiple pollen sensitization and pollen-food-latex syndromes that the allergist has to be aware of in order to accomplish an accurate diagnosis and successful treatment of allergic diseases. PMID:21293140

  8. Multiplex detection of food allergens and gluten.

    PubMed

    Cho, Chung Y; Nowatzke, William; Oliver, Kerry; Garber, Eric A E

    2015-05-01

    To help safeguard the food supply and detect the presence of undeclared food allergens and gluten, most producers and regulatory agencies rely on commercial test kits. Most of these are ELISAs with a few being PCR-based. These methods are very sensitive and analyte specific, requiring different assays to detect each of the different food allergens. Mass spectrometry offers an alternative approach whereby multiple allergens may be detected simultaneously. However, mass spectrometry requires expensive equipment, highly trained analysts, and several years before a quantitative approach can be achieved. Using multianalyte profiling (xMAP®) technology, a commercial multiplex test kit based on the use of established antibodies was developed for the simultaneous detection of up to 14 different food allergens plus gluten. The assay simultaneously detects crustacean seafood, egg, gluten, milk, peanut, soy, and nine tree nuts (almond, Brazil nut, cashew, coconut, hazelnut, macadamia, pine nut, pistachio, and walnut). By simultaneously performing multiple tests (typically two) for each analyte, this magnetic bead-based assay offers built-in confirmatory analyses without the need for additional resources. Twenty-five of the assays were performed on buffer extracted samples, while five were conducted on samples extracted using reduced-denatured conditions. Thus, complete analysis for all 14 allergens and gluten requires only two wells of a 96-well microtiter plate. This makes it possible to include in a single analytical run up to 48 samples. All 30 bead sets in this multiplex assay detected 5 ng/mL of food allergen and gluten with responses greater than background. In addition, 26 of the bead sets displayed signal/noise ratios of five or greater. The bead-based design makes this 30-plex assay expandable to incorporate new antibodies and capture/detector methodologies by ascribing these new detectors to any of the unassigned bead sets that are commercially available. PMID

  9. Human and animal health risk assessment of metal contamination in soil and plants from Ait Ammar abandoned iron mine, Morocco.

    PubMed

    Nouri, Mohamed; Haddioui, Abdelmajid

    2016-01-01

    The goal of this paper is to investigate metal pollution in food chain and assess the resulting health risks to native citizens in Ait Ammar village. The results showed that cadmium (Cd), lead (Pb), and copper (Cu) concentrations in animal organs were above the metal concentration safety limit. Nevertheless, soils and plants from mining area were contaminated with iron (Fe), chromium (Cr), zinc (Zn), and Cr, Cu, Zn respectively. Cd concentrations in almost animal organs were higher than the acceptable daily upper limit, suggesting human consumption of this livestock meat and offal may pose a health risk. The estimated intake of Pb and Cd for Ait Ammar population could be a cause of concern because it exceeded the Provisional Tolerable Weekly Intake (PTWI) proposed by Joint Expert Committee on Food Additives (JECFA) in this area. Thus, conducting regular periodic studies to assess the dietary intake of mentioned elements are recommended. PMID:26631396

  10. Hyperthermia as an immunotherapy strategy for cancer

    PubMed Central

    Skitzki, Joseph J.; Repasky, Elizabeth A.; Evans, Sharon S.

    2010-01-01

    The use of hyperthermia as an adjunct to cancer immunotherapy is supported by an increasing number of research data. Both preclinical and clinical data results have demonstrated improved antitumor immune responses with the addition of mild hyperthermia. The molecular mechanisms responsible for the improved immune reactivity observed in the presence of hyperthermia include the generation of Hsps, the activation of antigen presenting cells and changes in lymphocyte trafficking. Understanding these hyperthermia-induced processes can serve as the foundation for analyzing current clinical trials, as well as designing future trials in cancer immunotherapy. PMID:19513944

  11. Improving cancer immunotherapy with DNA methyltransferase inhibitors.

    PubMed

    Saleh, Mohammad H; Wang, Lei; Goldberg, Michael S

    2016-07-01

    Immunotherapy confers durable clinical benefit to melanoma, lung, and kidney cancer patients. Challengingly, most other solid tumors, including ovarian carcinoma, are not particularly responsive to immunotherapy, so combination with a complementary therapy may be beneficial. Recent findings suggest that epigenetic modifying drugs can prime antitumor immunity by increasing expression of tumor-associated antigens, chemokines, and activating ligands by cancer cells as well as cytokines by immune cells. This review, drawing from both preclinical and clinical data, describes some of the mechanisms of action that enable DNA methyltransferase inhibitors to facilitate the establishment of antitumor immunity. PMID:26646852

  12. Adoptive Immunotherapy for Cancer or Viruses

    PubMed Central

    Maus, Marcela V.; Fraietta, Joseph A.; Levine, Bruce L.; Kalos, Michael; Zhao, Yangbing; June, Carl H.

    2015-01-01

    Adoptive immunotherapy, or the infusion of lymphocytes, is a promising approach for the treatment of cancer and certain chronic viral infections. The application of the principles of synthetic biology to enhance T cell function has resulted in substantial increases in clinical efficacy. The primary challenge to the field is to identify tumor-specific targets to avoid off-tissue, on-target toxicity. Given recent advances in efficacy in numerous pilot trials, the next steps in clinical development will require multicenter trials in order to establish adoptive immunotherapy as a mainstream technology. PMID:24423116

  13. Human Tumor Antigens and Cancer Immunotherapy

    PubMed Central

    Vigneron, Nathalie

    2015-01-01

    With the recent developments of adoptive T cell therapies and the use of new monoclonal antibodies against the immune checkpoints, immunotherapy is at a turning point. Key players for the success of these therapies are the cytolytic T lymphocytes, which are a subset of T cells able to recognize and kill tumor cells. Here, I review the nature of the antigenic peptides recognized by these T cells and the processes involved in their presentation. I discuss the importance of understanding how each antigenic peptide is processed in the context of immunotherapy and vaccine delivery. PMID:26161423

  14. Structures of Two Major Allergens, Bla g 4 and Per a 4, From Cockroaches and Their IgE Binding Epitopes

    SciTech Connect

    Tan, Y.; Chan, S; Ong, T; Yit, L; Tiong, Y; Chew, F; Sivaraman, J; Mok, Y

    2009-01-01

    Inhalant allergens from cockroaches are an important cause of asthma to millions of individuals worldwide. Here we report for the first time the structures of two major cockroach allergens, Bla g 4 and Per a 4, that adopt a typical lipocalin fold but with distinct structural features as compared with other known lipocalin allergens. Both Bla g 4 and Per a 4 contain two long-range disulfide bonds linking the N and C termini to a beta-barrel. The C-terminal helix of Bla g 4 is bent and greatly extended toward the N terminus. Bla g 4 is found to be a monomer, whereas Per a 4 exists as a dimer in solution with a novel dimeric interface involving residues from loops at the top and bottom of the beta-barrel. Putative ligand binding sites of both allergens are determined by docking of the juvenile hormone III inside the beta-barrel and found to interact with the ligand using non-conserved residues. Bla g 4 and Per a 4 are found to be cross-reactive in sera IgE binding, at least in the Singaporean Chinese population tested. A major IgE binding epitope unique to Per a 4 is found on the loops at the bottom of the beta-barrel that may aid the development of hypoallergens for immunotherapy.

  15. Novel insights into immunotherapy for hepatitis B patients.

    PubMed

    Akbar, Sheikh Mohammad Fazle; Al-Mahtab, Mamun; Jahan, Munira; Yoshida, Osamu; Hiasa, Yoichi

    2016-01-01

    The possible use of immunotherapy for hepatitis B has emerged for two major reasons: (1) chronic hepatitis B (CHB) is an immune-mediated pathological condition, and (2) commercially available antiviral drugs are of limited efficacy. Although various immunomodulatory agents have been used to treat patients with CHB during the last three decades, there is currently no consensus among physicians and hepatologists regarding the suitability of immunotherapy for patients with CHB. However, new insights into immunotherapy for CHB have emerged; these may facilitate design of effective and tolerable immunotherapy regimens for these patients. This review provides a comprehensive overview of immunotherapy for CHB. PMID:26626120

  16. Microwave-Assisted Extraction of Oleanolic Acid and Ursolic Acid from Ligustrum lucidum Ait

    PubMed Central

    Xia, En-Qin; Wang, Bo-Wei; Xu, Xiang-Rong; Zhu, Li; Song, Yang; Li, Hua-Bin

    2011-01-01

    Oleanolic acid and ursolic acid are the main active components in fruit of Ligustrum lucidum Ait, and possess anticancer, antimutagenic, anti-inflammatory, antioxidative and antiprotozoal activities. In this study, microwave-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum was investigated with HPLC-photodiode array detection. Effects of several experimental parameters, such as type and concentration of extraction solvent, ratio of liquid to material, microwave power, extraction temperature and microwave time, on the extraction efficiencies of oleanolic acid and ursolic acid from Ligustrum lucidum were evaluated. The influence of experimental parameters on the extraction efficiency of ursolic acid was more significant than that of oleanolic acid (p < 0.05). The optimal extraction conditions were 80% ethanol aqueous solution, the ratio of material to liquid was 1:15, and extraction for 30 min at 70 °C under microwave irradiation of 500 W. Under optimal conditions, the yields of oleanolic acid and ursolic acid were 4.4 ± 0.20 mg/g and 5.8 ± 0.15 mg/g, respectively. The results obtained are helpful for the full utilization of Ligustrum lucidum, which also indicated that microwave-assisted extraction is a very useful method for extraction of oleanolic acid and ursolic acid from plant materials. PMID:21954361

  17. An Efficient Extraction Method for Fragrant Volatiles from Jasminum sambac (L.) Ait.

    PubMed

    Ye, Qiuping; Jin, Xinyi; Zhu, Xinliang; Lin, Tongxiang; Hao, Zhilong; Yang, Qian

    2015-01-01

    The sweet smell of aroma of Jasminum sambac (L.) Ait. is releasing while the flowers are blooming. Although components of volatile oil have been extensively studied, there are problematic issues, such as low efficiency of yield, flavour distortion. Here, the subcritical fluid extraction (SFE) was performed to extract fragrant volatiles from activated carbon that had absorbed the aroma of jasmine flowers. This novel method could effectively obtain main aromatic compounds with quality significantly better than solvent extraction (SE). Based on the analysis data with response surface methodology (RSM), we optimized the extraction conditions which consisted of a temperature of 44°C, a solvent-to-material ratio of 3.5:1, and an extraction time of 53 min. Under these conditions, the extraction yield was 4.91%. Furthermore, the key jasmine essence oil components, benzyl acetate and linalool, increase 7 fold and 2 fold respectively which lead to strong typical smell of the jasmine oil. The new method can reduce spicy components which lead to the essential oils smelling sweeter. Thus, the quality of the jasmine essence oil was dramatically improved and yields based on the key component increased dramatically. Our results provide a new effective technique for extracting fragrant volatiles from jasmine flowers. PMID:25891116

  18. Mucosal delivery of allergen peptides expressed by Lactococcus lactis inhibit allergic responses in a BALB/c mouse model.

    PubMed

    Ai, Chunqing; Zhang, Qiuxiang; Ding, Junrong; Wang, Gang; Liu, Xiaoming; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2016-02-01

    Allergen-specific immunotherapy (SIT) is considered to be the only curative treatment of allergy, but its safety is always affected by immunologic properties and quality of allergen. Recombinant allergen derivative could be a potential therapeutic strategy, but clinical studies showed that macromolecular derivatives could not avoid T cell-mediated side effects. In this study, five Der p2-derived peptides (DPs) containing major T cell epitopes of Der p2 were first artificially synthesized. Compared with Der p2 macromolecular derivative DM, these DPs not only fully eliminated IgE-binding capacity but also reduced T cells reactivity, suggesting these DPs could be better therapeutic molecules. For their application in vivo, Lactococcus lactis was engineered to express these DPs, and their protective effects were evaluated in BALB/c mice models. Western blot showed that all DPs could be produced in the recombinant strains. Mucosal delivery of these strains could inhibit Der p2-induced allergic responses in Der p2-sensitized mice, characterized by a reduction in specific IgE antibody and lung inflammatory responses. These protective effects were associated with an increase of specific IgG2a in serum and regulatory T cells in the mesenteric lymph nodes. On the whole, the suppressive effect induced by the DP mixture could be better than single DP, but a bit weaker than DM. These DPs could be promising candidate molecules for active vaccination and induction of tolerance, and thus promote the development of non-allergenic peptide in the treatment and prevention of allergy. PMID:26621801

  19. Molecular cloning, expression and immunological characterisation of Pas n 1, the major allergen of Bahia grass Paspalum notatum pollen.

    PubMed

    Davies, Janet M; Mittag, Diana; Dang, Thanh D; Symons, Karen; Voskamp, Astrid; Rolland, Jennifer M; O'Hehir, Robyn E

    2008-12-01

    Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a prolonged pollination season from spring to autumn. We aimed to clone and characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen-allergic patients presenting to a tertiary hospital allergy clinic were tested for IgE reactivity with Bahia grass pollen extract by skin prick testing, ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by rapid amplification of cDNA ends and cloned. Biological relevance of recombinant Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas n 1 cDNA has sequence homology with the beta-expansin 1 glycoprotein family and is more closely related to the maize pollen group 1 allergen (85% identity) than to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively). rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1 allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and cloned. rPas n 1 is immunologically active and is a valuable reagent for diagnosis and specific immunotherapy of grass pollen allergy. PMID:18817975

  20. Comparison of the basophil activation test versus the nasal provocation test in establishing eligibility for specific immunotherapy.

    PubMed

    Leśniak, Małgorzata; Dyga, Wojciech; Rusinek, Barbara; Mazur, Marcel; Czarnobilska, Ewa

    2016-08-25

    INTRODUCTION    Allergic rhinitis (AR) is the most common atopic disease. Specific immunotherapy (SIT) is the only effective treatment method for AR. In uncertain diagnostic cases, before establishing eligibility for SIT, nasal provocation tests (NPTs) should be performed. However, there are numerous contraindications to performing NPTs, and there is ongoing search for an alternative in vitro method. OBJECTIVES    The aim of the study was to determine whether a specific in vitro provocation, that is, the basophil activation test (BAT), may replace a specific in vivo provocation, that is, the NPT, in establishing patient's eligibility for SIT. PATIENTS AND METHODS    The study included 30 patients with AR caused by allergy to house dust mite or birch pollen, referred for SIT. The assessment of basophil activation by measuring CD63 antigen expression was performed using the Flow2 CAST test. Basophils were stimulated with allergen preparation (concentrations of 5000, 500, and 50 standardized biological units) used in NPTs. BAT results were expressed as stimulation index (SI) and basophil reactivity (BR). RESULTS    Allergen concentrations of 500 and 50 SBU proved to be appropriate for basophil stimulation. Median SI and BR were higher for positive NPT results than for negative NPT results (P <0.001). Sensitivity for SI and BR was in the range from 83% to 100%; specificity, from 78% to 89%; positive predictive value, from 75% to 87%; and negative predictive value, from 89% to 100%. We observed a high correlation of the analyzed parameters for the allergen concentrations of 500 and 50 SBU (range, 0.58-0.74; P <0.05). CONCLUSIONS    If there are contraindications to performing the NPT, BAT may be regarded as an alternative in establishing patients' eligibility for SIT. The optimal concentrations of allergen preparations are 500 and 50 SBU. Both SI and BR are good indicators of basophil activation. PMID:27578221

  1. Animal Allergens and Their Presence in the Environment

    PubMed Central

    Zahradnik, Eva; Raulf, Monika

    2014-01-01

    Exposure to animal allergens is a major risk factor for sensitization and allergic diseases. Besides mites and cockroaches, the most important animal allergens are derived from mammals. Cat and dog allergies affect the general population; whereas, allergies to rodents or cattle is an occupational problem. Exposure to animal allergens is not limited to direct contact to animals. Based on their aerodynamic properties, mammalian allergens easily become airborne, attach to clothing and hair, and can be spread from one environment to another. For example, the major cat allergen Fel d 1 was frequently found in homes without pets and in public buildings, including schools, day-care centers, and hospitals. Allergen concentrations in a particular environment showed high variability depending on numerous factors. Assessment of allergen exposure levels is a stepwise process that involves dust collection, allergen quantification, and data analysis. Whereas a number of different dust sampling strategies are used, ELISA assays have prevailed in the last years as the standard technique for quantification of allergen concentrations. This review focuses on allergens arising from domestic, farm, and laboratory animals and describes the ubiquity of mammalian allergens in the human environment. It includes an overview of exposure assessment studies carried out in different indoor settings (homes, schools, workplaces) using numerous sampling and analytical methods and summarizes significant factors influencing exposure levels. However, methodological differences among studies have contributed to the variability of the findings and make comparisons between studies difficult. Therefore, a general standardization of methods is needed and recommended. PMID:24624129

  2. Animal allergens and their presence in the environment.

    PubMed

    Zahradnik, Eva; Raulf, Monika

    2014-01-01

    Exposure to animal allergens is a major risk factor for sensitization and allergic diseases. Besides mites and cockroaches, the most important animal allergens are derived from mammals. Cat and dog allergies affect the general population; whereas, allergies to rodents or cattle is an occupational problem. Exposure to animal allergens is not limited to direct contact to animals. Based on their aerodynamic properties, mammalian allergens easily become airborne, attach to clothing and hair, and can be spread from one environment to another. For example, the major cat allergen Fel d 1 was frequently found in homes without pets and in public buildings, including schools, day-care centers, and hospitals. Allergen concentrations in a particular environment showed high variability depending on numerous factors. Assessment of allergen exposure levels is a stepwise process that involves dust collection, allergen quantification, and data analysis. Whereas a number of different dust sampling strategies are used, ELISA assays have prevailed in the last years as the standard technique for quantification of allergen concentrations. This review focuses on allergens arising from domestic, farm, and laboratory animals and describes the ubiquity of mammalian allergens in the human environment. It includes an overview of exposure assessment studies carried out in different indoor settings (homes, schools, workplaces) using numerous sampling and analytical methods and summarizes significant factors influencing exposure levels. However, methodological differences among studies have contributed to the variability of the findings and make comparisons between studies difficult. Therefore, a general standardization of methods is needed and recommended. PMID:24624129

  3. Current developments for improving efficacy of allergy vaccines.

    PubMed

    Sandrini, Alessandra; Rolland, Jennifer M; O'Hehir, Robyn E

    2015-01-01

    Allergic diseases are prevalent worldwide. Allergen immunotherapy (AIT) is a current treatment for allergy, leading to modification of the natural course of disease. Mechanisms of efficacy include Treg through release of IL-10 and TGF-β and specific IgG4 blocking antibodies. Subcutaneous and sublingual routes are popular, but uptake is limited by inconvenience and safety concerns. Inclusion criteria limit application to a small proportion of allergic patients. New forms of immunotherapy are being investigated for more efficacious, convenient and safer options with promising advances in recent years. The rationale of reducing vaccine allergenicity to increase safety while improving immunogenicity led to investigation of T-cell epitope-based peptides and recombinant allergen derivatives. Additionally, different routes of administration and adjuvants and adjunct therapies are being explored. This review discusses the current status of AIT and recent advances to improve clinical efficacy, safety and long-term immune tolerance. PMID:26013124

  4. Biomarkers for glioma immunotherapy: the next generation

    PubMed Central

    Ung, Timothy H.; Neira, Justin A.; Canoll, Peter; Bruce, Jeffrey N.

    2015-01-01

    The term “biomarker” historically refers to a single parameter, such as the expression level of a gene or a radiographic pattern, used to indicate a broader biological state. Molecular indicators have been applied to several aspects of cancer therapy: to describe the genotypic and phenotypic state of neoplastic tissue for prognosis, to predict susceptibility to anti-proliferative agents, to validate the presence of specific drug targets, and to evaluate responsiveness to therapy. For glioblastoma (GBM), immunohistochemical and radiographic biomarkers accessible to the clinical lab have informed traditional regimens, but while immunotherapies have emerged as potentially disruptive weapons against this diffusely infiltrating, heterogeneous tumor, biomarkers with strong predictive power have not been fully established. The cancer immunotherapy field, through the recently accelerated expansion of trials, is currently leveraging this wealth of clinical and biological data to define and revise the use of biomarkers for improving prognostic accuracy, personalization of therapy, and evaluation of responses across the wide variety of tumors. Technological advancements in DNA sequencing, cytometry, and microscopy have facilitated the exploration of more integrated, high-dimensional profiling of the disease system—incorporating both immune and tumor parameters—rather than single metrics, as biomarkers for therapeutic sensitivity. Here we discuss the utility of traditional GBM biomarkers in immunotherapy and how the impending transformation of the biomarker paradigm—from single markers to integrated profiles—may offer the key to bringing predictive, personalized immunotherapy to GBM patients. PMID:25724916

  5. Topical immunotherapy with diphenylcyclopropenone-induced vitiligo.

    PubMed

    Kutlubay, Zekayi; Engin, Burhan; Songur, Abdullah; Serdaroglu, Server; Tuzun, Yalcin

    2016-08-01

    Topical immunotherapy made by diphenylcyclopropenone (DPCP) is an alternative treatment that can be used safely and efficaciously in recalcitrant alopecia areata patients. DPCP-induced vitiligo is a rare, but documented, unwanted side effect. The real mechanism of DPCP-induced vitiligo is not well known. PMID:26963903

  6. Developing Strategies in the Immunotherapy of Leukemias

    PubMed Central

    Brayer, Jason B.; Pinilla-Ibarz, Javier

    2015-01-01

    Background In the current treatment paradigms for leukemias, hematopoietic stem cell transplant (HSCT) is considered the best option with a curative potential although more often than not it simply delays disease progression. Advances are needed, both in current therapies and in the development of new strategies. Partly from studying the nuances of the curative potential of stem cell transplant, we have come to appreciate the relevance of the immune response and the potential of immunotherapy. Methods This review article summarizes the recent advances in the field of immunology and immunotherapy for leukemia. Results In passive immunotherapy, recent progress in chimeric T-cell antigen receptor technology has been encouraging. In active immunotherapy, a cancer vaccine may potentially enhance HSCT. An overview of various clinical studies of peptide vaccination strategies focusing on molecular targets such as the Wilms’ tumor gene 1 (WT1), proteinase 3 (PR3), and receptor for hyaluronan acid-mediated motility (RHAMM) is provided. Cell-based vaccination strategies are also briefly explored. Conclusions The immune system clearly has the capacity to recognize and react to leukemic cells, and recent evidence directs our attention to the importance of mounting inflammatory and CD4 T-cell responses to complement and support the cytotoxic activity elicited by peptide vaccines. PMID:23302907

  7. Role of IL-2 in cancer immunotherapy.

    PubMed

    Jiang, Tao; Zhou, Caicun; Ren, Shengxiang

    2016-06-01

    Interleukin-2 (IL-2) is one of the key cytokines with pleiotropic effects on immune system. It has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. Recent progress has been made in our understanding of IL-2 in regulating lymphocytes that has led to exciting new directions for cancer immunotherapy. While improved IL-2 formulations might be used as monotherapies, their combination with other anticancer immunotherapies, such as adoptive cell transfer regimens, antigen-specific vaccination, and blockade of immune checkpoint inhibitory molecules, for example cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) mono-antibodies, would held the promise of treating metastatic cancer. Despite the comprehensive studies of IL-2 on immune system have established the application of IL-2 for cancer immunotherapy, a number of poignant obstacles remain for future research. In the present review, we will focus on the key biological features of IL-2, current applications, limitations, and future directions of IL-2 in cancer immunotherapy. PMID:27471638

  8. Adapting conventional cancer treatment for immunotherapy.

    PubMed

    Qiao, Jian; Liu, Zhida; Fu, Yang-Xin

    2016-05-01

    The efficacy of directly killing tumors by conventional cancer therapies, such as chemotherapy and radiotherapy, has been for several decades well established. But, a suppressed immune response might become a lethal side effect after repeated cycles of intensive treatment. Recently, achievements in immune checkpoint inhibitors and adoptive T cell-mediated immunotherapies have resulted in changes in frontline management of advanced cancer diseases. However, accumulated evidence indicates that immunotherapeutic and conventional strategies alone are often ineffective to eradicate big tumors or metastasis. To improve the outcomes of treatment for advanced cancer diseases, the combination of conventional cancer treatment with various immunotherapeutic approaches has been attempted and has shown potential synergistic effects. Recent studies have unexpectedly demonstrated that some strategies of conventional cancer treatment can regulate the immune response positively, thus the understanding of how to adapt conventional treatment for immunotherapy is crucial to the design of effective combination therapy of conventional treatment with immunotherapy. Here, we review both experimental and clinical studies on the therapeutic effect and its mechanisms of combining conventional therapy with immunotherapy in treatment of cancer. PMID:26910191

  9. Biomarkers and correlative endpoints for immunotherapy trials.

    PubMed

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer. PMID:23714525

  10. Biomarkers for Immunotherapy: Current Developments and Challenges.

    PubMed

    Spencer, Kristen R; Wang, Jianfeng; Silk, Ann W; Ganesan, Shridar; Kaufman, Howard L; Mehnert, Janice M

    2016-01-01

    Immunotherapy has revolutionized cancer therapy and has been named the cancer advance of the year for 2016. Checkpoint inhibitors have demonstrated unprecedented rates of durable responses in some of the most difficult-to-treat cancers; however, many treated patients do not respond, and the potential for serious side effects exists. There is a growing need to identify biomarkers that will improve the selection of patients who will best respond to therapy, further elucidate drug mechanisms of action, and help tailor therapy regimens. Biomarkers are being explored at the soluble, cellular, and genomic levels, and examples in immunotherapy include serum proteins, tumor-specific receptor expression patterns, factors in the tumor microenvironment, circulating immune and tumor cells, and host genomic factors. The search for reliable biomarkers is limited by our incomplete understanding of how immunotherapies modify the already complex immune response to cancer, as well as the contribution of immuno-editing to a dynamic and inducible tumor microenvironment and immune milieu. Furthermore, there has been little extension of any candidate assay into large, prospective studies, and the lack of standardization in measurement and interpretation restricts their validity. Both tumor-infiltrating lymphocytes and PD-L1 expression within the tumor microenvironment have been recognized as having both prognostic and predictive value for patients treated with immunotherapy. Alternately, a larger panel of gene signatures, chemokines, and other factors that correlate with response has been proposed. In this article, we will explore the status of current biomarker candidates. PMID:27249758

  11. Standardization and Regulation of Allergen Products in the European Union.

    PubMed

    Zimmer, Julia; Vieths, Stefan; Kaul, Susanne

    2016-03-01

    Product-specific standardization is of prime importance to ensure persistent quality, safety, and efficacy of allergen products. The regulatory framework in the EU has induced great advancements in the field in the last years although national implementation still remains heterogeneous. Scores of methods for quantification of individual allergen molecules are developed each year and also the challenging characterization of chemically modified allergen products is progressing. However, despite the unquestionable increase in knowledge and the subsequent improvements in control of quality parameters of allergen products, an important aim has not been reached yet, namely cross-product comparability. Still, comparison of allergen product potency, either based on total allergenic activity or individual allergen molecule content, is not possible due to a lack of standard reference preparations in conjunction with validated standard methods. This review aims at presenting the most recent developments in product-specific standardization as well as activities to facilitate cross-product comparability in the EU. PMID:26874849

  12. Allergen-Specific CD4(+) T Cells in Human Asthma.

    PubMed

    Ling, Morris F; Luster, Andrew D

    2016-03-01

    In allergic asthma, aeroallergen exposure of sensitized individuals mobilizes robust innate and adaptive airway immune responses, stimulating eosinophilic airway inflammation and the activation and infiltration of allergen-specific CD4(+) T cells into the airways. Allergen-specific CD4(+) T cells are thought to be central players in the asthmatic response as they specifically recognize the allergen and initiate and orchestrate the asthmatic inflammatory response. In this article, we briefly review the role of allergen-specific CD4(+) T cells in the pathogenesis of human allergic airway inflammation in allergic individuals, discuss the use of allergen-major histocompatibility complex class II tetramers to characterize allergen-specific CD4(+) T cells, and highlight current gaps in knowledge and directions for future research pertaining to the role of allergen-specific CD4(+) T cells in human asthma. PMID:27027948

  13. INDUCTION OF PLANT ALLERGENS BY ENVIRONMENTAL AGENTS

    EPA Science Inventory

    The specific objectives of the project and the progress toward meeting these objectives are listed below:

    Identify up to Three Environmental Exposures That Induce the Production of an Allergenic Protein in the Mountain Cedar Tree by Examining the Effects of Exposu...

  14. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIAE

    EPA Science Inventory

    Introduction

    The goal of this project is the identification and characterization of allergens from the fungus Metarhizium anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaer...

  15. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIEA

    EPA Science Inventory

    The goal of this project is the identification and characterization of allergens from the fungus M. Anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaerosol contamination. One of ...

  16. IDENTIFYING IMPORTANT ALLERGENS USING MASS SPECTROMETRY

    EPA Science Inventory

    The US EPA's mission is to protect human health and the environment. Fungal allergens are major potential source of allergy based disease like asthma which is now increasing, according to the Centers for Disease Control and Prevention, at epidemic rates. The Cooperative Agreemen...

  17. Allergenic pollen and pollen allergy in Europe.

    PubMed

    D'Amato, G; Cecchi, L; Bonini, S; Nunes, C; Annesi-Maesano, I; Behrendt, H; Liccardi, G; Popov, T; van Cauwenberge, P

    2007-09-01

    The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas. Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers. Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases. PMID:17521313

  18. ASSESSING ALLERGENICITY OF INDOOR AIR FUNGAL CONTAMINANTS

    EPA Science Inventory

    Assessing Allergenicity of Indoor Air Fungal Contaminants
    M D W Ward1, M E Viana2, N Haykal-Coates1, L B Copeland1, S H Gavett1, and MJ K Selgrade1. 1US EPA, ORD, NHEERL, RTP, NC, USA. 2NCSU, CVM, Raleigh, NC, USA.
    Rationale: The indoor environment has increased in impor...

  19. 205 Allergy Training and Immunotherapy in Latin America: How Survey-Results Lead to a Regional Overview

    PubMed Central

    Gomez, R. Maximiliano; Linnemann, Désirée Larenas; Passalacqua, Giovanni; González-Díaz, Sandra; Coce, Victor H.; Canonica, Giorgio Walter; Baena-Cagnani, Carlos E.

    2012-01-01

    Background In April 2011 a group of Latin American (LA) allergy experts, leaders in their countries in the area of immunotherapy, met in Cordoba, Argentina, to discuss how allergy and allergen-specific immunotherapy (ASIT) can be improved in the region. The need for a situational sketch was expressed. Methods A questionnaire on allergy training (AT), ASIT, extracts and legislation was sent out to 22 leaders in the field of nine LA countries to obtain an overview of the LA situation. Results Results are presented with descriptive statistics. All 22 questionnaires were returned (9 countries). AT in 56% of the surveyed LA countries is at the third-level of medical care, after a core-training of 2 to 3 years internal medicine or pediatrics; in 3 countries it is a second-level career and in one country there is no AT. Board certification with exam is only mandatory in a third of the countries; recertification being obtained without exam. Mostly, training is in general allergy; pediatric AT only exists in 2 countries. Both sublingual (SLIT, only in the form of drops) and subcutaneous (SCIT) immunotherapy are practiced in all countries, from the age of 3 years (mean, range 1–5 years) onward. As no strict legislation exists IT can be managed by non-allergists in 7/9 countries. Mixed extracts are used with mostly 3 to 5 allergens/vial (range 2 to 6-10 allergens/vial) and all countries have bacterial vaccine. SCIT extracts come from US and European (89%) and 56% local providers. SLIT extracts are almost exclusively from Europe (Spain), but in Argentine, Brazil, and Mexico also local SLIT extracts exist. There is rudimentary regulation concerning extract potency in 2 countries. IT is generally paid for by private patients. Insurance companies reimburse IT in 56% of the countries, the social security system in 33% and in one country selected third level governmental hospitals supply IT. Publications on adverse events with IT are starting to appear (3 countries) and 3

  20. Emerging Opportunities and Challenges in Cancer Immunotherapy.

    PubMed

    Whiteside, Theresa L; Demaria, Sandra; Rodriguez-Ruiz, Maria E; Zarour, Hassane M; Melero, Ignacio

    2016-04-15

    Immunotherapy strategies against cancer are emerging as powerful weapons for treatment of this disease. The success of checkpoint inhibitors against metastatic melanoma and adoptive T-cell therapy with chimeric antigen receptor T cells against B-cell-derived leukemias and lymphomas are only two examples of developments that are changing the paradigms of clinical cancer management. These changes are a result of many years of intense research into complex and interrelated cellular and molecular mechanisms controling immune responses. Promising advances come from the discovery of cancer mutation-encoded neoantigens, improvements in vaccine development, progress in delivery of cellular therapies, and impressive achievements in biotechnology. As a result, radical transformation of cancer treatment is taking place in which conventional cancer treatments are being integrated with immunotherapeutic agents. Many clinical trials are in progress testing potential synergistic effects of treatments combining immunotherapy with other therapies. Much remains to be learned about the selection, delivery, and off-target effects of immunotherapy used alone or in combination. The existence of numerous escape mechanisms from the host immune system that human tumors have evolved still is a barrier to success. Efforts to understand the rules of immune cell dysfunction and of cancer-associated local and systemic immune suppression are providing new insights and fuel the enthusiasm for new therapeutic strategies. In the future, it might be possible to tailor immune therapy for each cancer patient. The use of new immune biomarkers and the ability to assess responses to therapy by noninvasive monitoring promise to improve early cancer diagnosis and prognosis. Personalized immunotherapy based on individual genetic, molecular, and immune profiling is a potentially achievable future goal. The current excitement for immunotherapy is justified in view of many existing opportunities for harnessing

  1. Amyloid beta peptide immunotherapy in Alzheimer disease.

    PubMed

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. PMID:25459121

  2. Purified Timothy grass pollen major allergen Phl p 1 may contribute to the modulation of allergic responses through a pleiotropic induction of cytokines and chemokines from airway epithelial cells

    PubMed Central

    Röschmann, K I L; van Kuijen, A-M; Luiten, S; Jonker, M J; Breit, T M; Fokkens, W J; Petersen, A; van Drunen, C M

    2012-01-01

    By definition, allergens are proteins with the ability to elicit powerful T helper lymphocyte type 2 (Th2) responses, culminating in immunoglobulin (Ig)E antibody production. Why specific proteins cause aberrant immune responses has remained largely unanswered. Recent data suggest that there may be several molecular paths that may affect allergenicity of proteins. The focus of this study is the response of airway epithelium to a major allergen from Phleum pratense Phl p 1. Instead of focusing on a few genes and proteins that might be affected by the major allergen, our aim was to obtain a broader view on the immune stimulatory capacity of Phl p 1. We therefore performed detailed analysis on mRNA and protein level by using a microarray approach to define Phl p 1-induced gene expression. We found that this allergen induces modulation and release of a broad range of mediators, indicating it to be a powerful trigger of the immune system. We were able to show that genes belonging to the GO cluster ‘cell communication’ were among the most prominent functional groups, which is also reflected in cytokines and chemokines building centres in a computational model of direct gene interaction. Further detailed comparison of grass pollen extract (GPE)- and Phl p 1-induced gene expression might be beneficial with regard to the application of single components within diagnosis and immunotherapy. PMID:22288584

  3. Choosing the optimal dose in sublingual immunotherapy: Rationale for the 300 index of reactivity dose.

    PubMed

    Demoly, Pascal; Passalacqua, Gianni; Calderon, Moises A; Yalaoui, Tarik

    2015-01-01

    Sublingual immunotherapy (SLIT) is an effective and well-tolerated method of treating allergic respiratory diseases associated with seasonal and perennial allergens. In contrast to the subcutaneous route, SLIT requires a much greater amount of antigen to achieve a clinical effect. Many studies have shown that SLIT involves a dose-response relationship, and therefore it is important to use a proven clinically effective dose from the onset of treatment, because low doses are ineffective and very high doses may increase the risk of side effects. A well-defined standardization of allergen content is also crucial to ensure consistent quality, potency and appropriate immunomodulatory action of the SLIT product. Several methods of measuring antigenicity are used by manufacturers of SLIT products, including the index of reactivity (IR), standardized quality tablet unit, and bioequivalent allergy unit. A large body of evidence has established the 300 IR dose of SLIT as offering optimal efficacy and tolerability for allergic rhinitis due to grass and birch pollen and HDM, and HDM-induced moderate, persistent allergic asthma. The 300 IR dose also offers consistency of dosing across a variety of different allergens, and is associated with higher rates of adherence and patient satisfaction. Studies in patients with grass pollen allergies showed that the 300 IR dose has a rapid onset of action, is effective in both adults and children in the short term and, when administered pre-coseasonally in the long term, and maintains the clinical benefit, even after cessation of treatment. In patients with HDM-associated AR and/or asthma, the 300 IR dose also demonstrated significant improvements in symptoms and quality of life, and significantly decreased use of symptomatic medication. The 300 IR dose is well tolerated, with adverse events generally being of mild or moderate severity, declining in frequency and severity over time and in the subsequent courses. We discuss herein the most

  4. Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011.

    PubMed

    Martinez Forero, Ivan; Okada, Hideho; Topalian, Suzanne L; Gajewski, Thomas F; Korman, Alan J; Melero, Ignacio

    2012-01-01

    Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and "perceived" business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace. PMID

  5. Organ-specific metabolic responses to drought in Pinus pinaster Ait.

    PubMed

    de Miguel, Marina; Guevara, M Ángeles; Sánchez-Gómez, David; de María, Nuria; Díaz, Luis Manuel; Mancha, Jose A; Fernández de Simón, Brígida; Cadahía, Estrella; Desai, Nalini; Aranda, Ismael; Cervera, María-Teresa

    2016-05-01

    Drought is an important driver of plant survival, growth, and distribution. Water deficit affects different pathways of metabolism, depending on plant organ. While previous studies have mainly focused on the metabolic drought response of a single organ, analysis of metabolic differences between organs is essential to achieve an integrated understanding of the whole plant response. In this work, untargeted metabolic profiling was used to examine the response of roots, stems, adult and juvenile needles from Pinus pinaster Ait. full-sib individuals, subjected to a moderate and long lasting drought period. Cyclitols content showed a significant alteration, in response to drought in all organs examined, but other metabolites increased or decreased differentially depending on the analyzed organ. While a high number of flavonoids were only detected in aerial organs, an induction of the glutathione pathway was mainly detected in roots. This result may reflect different antioxidant mechanisms activated in aerial organs and roots. Metabolic changes were more remarkable in roots than in the other organs, highlighting its prominent role in the response to water stress. Significant changes in flavonoids and ascorbate metabolism were also observed between adult and juvenile needles, consistent with previously proven differential functional responses between the two developmental stages. Genetic polymorphisms in candidate genes coding for a Myb1 transcription factor and a malate dehydrogenase (EC 1.1.1.37) were associated with different concentration of phenylalanine, phenylpropanoids and malate, respectively. The results obtained will support further research on metabolites and genes potentially involved in functional mechanisms related to drought tolerance in trees. PMID:26897116

  6. Novel structure of cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment

    PubMed Central

    Mueller, Geoffrey A.; Pedersen, Lars C.; Lih, Fred B.; Glesner, Jill; Moon, Andrea F.; Chapman, Martin D.; Tomer, Kenneth B.; London, Robert E.; Pomés, Anna

    2013-01-01

    Background Sensitization to cockroach allergens is a major risk factor for asthma. The cockroach allergen Bla g 1 has multiple repeats of ~100 amino acids, but the fold of the protein and the biological function are unknown. Objective To determine the structure of Bla g 1, investigate the implications for allergic disease, and standardize cockroach exposure assays. Methods Natural Bla g 1 and recombinant constructs were compared by ELISA using specific murine IgG and human IgE. The structure of Bla g 1 was determined by X-ray crystallography. Mass spectrometry and NMR were utilized to examine ligand-binding properties of the allergen. Results The structure of a recombinant Bla g 1 construct with comparable IgE and IgG reactivity to the natural allergen was solved by X-ray crystallography. The Bla g 1 repeat forms a novel fold with 6 helices. Two repeats encapsulate a large and nearly spherical hydrophobic cavity, defining the basic structural unit. Lipids in the cavity varied depending on the allergen origin. Palmitic, oleic and stearic acids were associated with nBla g 1 from cockroach frass. One Unit of Bla g 1 was equivalent to 104 ng of allergen. Conclusions Bla g 1 has a novel fold with a capacity to bind various lipids, which suggests a digestive function associated with non-specific transport of lipid molecules in cockroaches. Defining the basic structural unit of Bla g 1 facilitates the standardization of assays in absolute units for the assessment of environmental allergen exposure. PMID:23915714

  7. Tree pollen allergens-an update from a molecular perspective.

    PubMed

    Asam, C; Hofer, H; Wolf, M; Aglas, L; Wallner, M

    2015-10-01

    It is estimated that pollen allergies affect approximately 40% of allergic individuals. In general, tree pollen allergies are mainly elicited by allergenic trees belonging to the orders Fagales, Lamiales, Proteales, and Pinales. Over 25 years ago, the gene encoding the major birch pollen allergen Bet v 1 was the first such gene to be cloned and its product characterized. Since that time, 53 tree pollen allergens have been identified and acknowledged by the WHO/IUIS allergen nomenclature subcommittee. Molecule-based profiling of allergic sensitization has helped to elucidate the immunological connections of allergen cross-reactivity, whereas advances in biochemistry have revealed structural and functional aspects of allergenic proteins. In this review, we provide a comprehensive overview of the present knowledge of the molecular aspects of tree pollen allergens. We analyze the geographic distribution of allergenic trees, discuss factors pivotal for allergic sensitization, and describe the role of tree pollen panallergens. Novel allergenic tree species as well as tree pollen allergens are continually being identified, making research in this field highly competitive and instrumental for clinical applications. PMID:26186076

  8. Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.

    PubMed Central

    Neudecker, Philipp; Lehmann, Katrin; Nerkamp, Jörg; Haase, Tanja; Wangorsch, Andrea; Fötisch, Kay; Hoffmann, Silke; Rösch, Paul; Vieths, Stefan; Scheurer, Stephan

    2003-01-01

    Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. PMID:12943529

  9. [Evaluation of the total biological activity and allergenic composition of allergenic extracts].

    PubMed

    Lombardero, M; González, R; Duffort, O; Juan, F; Ayuso, R; Ventas, P; Cortés, C; Carreira, J

    1986-01-01

    In the present study, a complete procedure is presented in order to standardize allergenic extracts, the meaning of which is the measurement of the total allergenic activity and the determination of the allergenic composition. The measurement of the biological activity comprises 2 steps: Preparation of Reference Extracts and determination of their "in vivo" activity. Evaluation of the total allergenic activity of extracts for clinical use. Reference extracts were prepared from the main allergens and their "in vivo" biological activity was determined by a quantitative skin prick test in a sample of at least 30 allergic patients. By definition, the protein concentration of Reference Extract that produces, in the allergic population, a geometric mean wheal of 75 mm.2 has an activity of 100 biological units (BUs). The determination of the biological activity of a problem extract is made by RAST inhibition. The sample is compared with the corresponding Reference Extract by this technique and, from this comparison, it is possible to quantify the activity of the problem extract in biologic units (BUs) with clinical significance. Likewise, different techniques have been used to determine the allergenic composition of extracts. These techniques comprise 2 steps: Separation of the components of the extract. Identification of the components that bind specific human IgE. The separation of the components of the extract has been carried out by isoelectric focusing (IEF) and electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). In order to identify the allergenic components, an immunoblotting technique has been employed. The separated components in the IEF gel or SDS-PAGE gel are transferred to a nitrocellulose sheet and later on, this membrane is overlaid with a serum pool from allergic patients and a mouse monoclonal anti-human IgE, labelled with 125I. Finally, the autoradiography of the nitrocellulose membrane is obtained. In this way it is possible to compare

  10. First National Survey of Lead and Allergens in Housing: survey design and methods for the allergen and endotoxin components.

    PubMed Central

    Vojta, Patrick J; Friedman, Warren; Marker, David A; Clickner, Robert; Rogers, John W; Viet, Susan M; Muilenberg, Michael L; Thorne, Peter S; Arbes, Samuel J; Zeldin, Darryl C

    2002-01-01

    From July 1998 to August 1999, the U.S. Department of Housing and Urban Development and the National Institute of Environmental Health Sciences conducted the first National Survey of Lead and Allergens in Housing. The purpose of the survey was to assess children's potential household exposure to lead, allergens, and bacterial endotoxins. We surveyed a sample of 831 homes, representing 96 million permanently occupied, noninstitutional housing units that permit resident children. We administered questionnaires to household members, made home observations, and took environmental samples. This article provides general background information on the survey, an overview of the survey design, and a description of the data collection and laboratory methods pertaining to the allergen and endotoxin components. We collected dust samples from a bed, the bedroom floor, a sofa or chair, the living room floor, the kitchen floor, and a basement floor and analyzed them for cockroach allergen Bla g 1, the dust mite allergens Der f 1 and Der p 1, the cat allergen Fel d 1, the dog allergen Can f 1, the rodent allergens Rat n 1 and mouse urinary protein, allergens of the fungus Alternaria alternata, and endotoxin. This article provides the essential context for subsequent reports that will describe the prevalence of allergens and endotoxin in U.S. households, their distribution by various housing characteristics, and their associations with allergic diseases such as asthma and rhinitis. PMID:12003758

  11. Effects of Nasal Corticosteroids on Boosts of Systemic Allergen-Specific IgE Production Induced by Nasal Allergen Exposure

    PubMed Central

    Egger, Cornelia; Lupinek, Christian; Ristl, Robin; Lemell, Patrick; Horak, Friedrich; Zieglmayer, Petra; Spitzauer, Susanne; Valenta, Rudolf; Niederberger, Verena

    2015-01-01

    Background Allergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear. Aim Here we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure. Methods Subjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG1–4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter. Results Nasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects. Conclusion In conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure. Trial Registration http://clinicaltrials.gov/ NCT00755066 PMID:25705889

  12. Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: an in vitro study.

    PubMed

    Siman, Isabella Lima; de Aquino, Lais Martins; Ynoue, Leandro Hideki; Miranda, Juliana Silva; Pajuaba, Ana Claudia Arantes Marquez; Cunha-Júnior, Jair Pereira; Silva, Deise Aparecida Oliveira; Taketomi, Ernesto Akio

    2013-01-01

    One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%-51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT. PMID:24069042

  13. Induction of immune tolerance in asthmatic mice by vaccination with DNA encoding an allergen-cytotoxic T lymphocyte-associated antigen 4 combination.

    PubMed

    Zhang, Fang; Huang, Gang; Hu, Bo; Song, Yong; Shi, Yi

    2011-05-01

    Allergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA₃.₁) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed and transfected into COS-7 cells to obtain the fusion protein OVA-CTLA-4, which was able to bind the B7 ligand on dendritic cells (DCs), and induced CD25⁺ Foxp3⁺ regulatory T (Treg) cells by the coculture of naive CD4⁺ T cells with DCs in vitro. In an animal study, BALB/c mice were sensitized and challenged with OVA to establish the asthmatic model. Vaccination with a high dose of OVA-CTLA-4-pcDNA₃.₁ significantly decreased interleukin-4 (IL-4) and IL-5 levels and eosinophil counts and prevented OVA-induced reduction of the gamma interferon level in the bronchoalveolar lavage fluid. In addition, these mice suffered less severe airway inflammation and had lower levels of OVA-specific IgE and IgG1 titers in serum. Also, high-dose OVA-CTLA-4-pcDNA₃.₁ vaccination inhibited the development of airway hyperreactivity and prevented OVA-induced reduction of the percentages of Foxp3⁺ Treg cells in the spleen. Our results indicate that a high dose of allergen-CTLA-4-encoding DNA vaccine was more effective in preventing an allergen-induced Th2-skewed immune response through the induction of Treg cells and may be a new alternative therapy for asthma. PMID:21346053

  14. Allergenic Characterization of a Novel Allergen, Homologous to Chymotrypsin, from German Cockroach

    PubMed Central

    Jeong, Kyoung Yong; Son, Mina; Lee, Jae-Hyun; Hong, Chein-Soo

    2015-01-01

    Purpose Cockroach feces are known to be rich in IgE-reactive components. Various protease allergens were identified by proteomic analysis of German cockroach fecal extract in a previous study. In this study, we characterized a novel allergen, a chymotrypsin-like serine protease. Methods A cDNA sequence homologous to chymotrypsin was obtained by analysis of German cockroach expressed sequence tag (EST) clones. The recombinant chymotrypsins from the German cockroach and house dust mite (Der f 6) were expressed in Escherichia coli using the pEXP5NT/TOPO vector system, and their allergenicity was investigated by ELISA. Results The deduced amino acid sequence of German cockroach chymotrypsin showed 32.7 to 43.1% identity with mite group 3 (trypsin) and group 6 (chymotrypsin) allergens. Sera from 8 of 28 German cockroach allergy subjects (28.6%) showed IgE binding to the recombinant protein. IgE binding to the recombinant cockroach chymotrypsin was inhibited by house dust mite chymotrypsin Der f 6, while it minimally inhibited the German cockroach whole body extract. Conclusions A novel allergen homologous to chymotrypsin was identified from the German cockroach and was cross-reactive with Der f 6. PMID:25749759

  15. Mechanism of Anti-α-Synuclein Immunotherapy

    PubMed Central

    Lee, Jun Sung; Lee, Seung-Jae

    2016-01-01

    Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson’s disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy. PMID:26828212

  16. Immunotherapy in Chronic Lymphocytic Leukaemia (CLL).

    PubMed

    Freeman, Ciara L; Gribben, John G

    2016-02-01

    Chronic lymphocytic leukaemia (CLL) is well known to generate impaired immune responses in the host, with the malignant clone residing in well-vascularized tissues and circulating in peripheral blood but also in close proximity to effector cells that are capable, if activated appropriately, of eliciting a cytotoxic response. These, combined with the fact that this is frequently a condition affecting older patients with co-morbidities often unfit for many "traditional" cytotoxic agents with their significant associated toxicities, make CLL an ideal candidate for the development of immunotherapy. The impressive results seen with the addition of a monoclonal antibody, rituximab, to a chemotherapy backbone, for example, is testament to how effective harnessing an immune-mediated response in CLL can be. This review serves to outline the available arsenal of immunotherapies-past and present-demonstrated to have potential in CLL with some perspectives on how the landscape in this disease may evolve in the future. PMID:26857283

  17. RNA-Based Vaccines in Cancer Immunotherapy

    PubMed Central

    McNamara, Megan A.; Nair, Smita K.; Holl, Eda K.

    2015-01-01

    RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy. PMID:26665011

  18. Development of PROSTVAC immunotherapy in prostate cancer.

    PubMed

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  19. Immunological landscape and immunotherapy of hepatocellular carcinoma.

    PubMed

    Prieto, Jesús; Melero, Ignacio; Sangro, Bruno

    2015-12-01

    Advanced hepatocellular carcinoma (HCC) is a serious therapeutic challenge and targeted therapies only provide a modest benefit in terms of overall survival. Novel approaches are urgently needed for the treatment of this prevalent malignancy. Evidence demonstrating the antigenicity of tumour cells, the discovery that immune checkpoint molecules have an essential role in immune evasion of tumour cells, and the impressive clinical results achieved by blocking these inhibitory receptors, are revolutionizing cancer immunotherapy. Here, we review the data on HCC immunogenicity, the mechanisms for HCC immune subversion and the different immunotherapies that have been tested to treat HCC. Taking into account the multiplicity of hyperadditive immunosuppressive forces acting within the HCC microenvironment, a combinatorial approach is advised. Strategies include combinations of systemic immunomodulation and gene therapy, cell therapy or virotherapy. PMID:26484443

  20. Development of PROSTVAC immunotherapy in prostate cancer

    PubMed Central

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  1. [Transcutaneous applications for vaccination and immunotherapy].

    PubMed

    Krämer, Isabel; Zabel, Franziska; Kündig, Thomas M; Johansen, Pål

    2014-10-15

    Although Edward Jenner applied the first vaccines by scratching cow pox material into the skin, the profound immunological properties of the skin have become evident through research and discoveries only in the last 20 years. The immunological cells in the epidermis and the dermis are suitable targets for transcutaneous vaccination and immunotherapy. However, as the skin represents a natural barrier for topically administered large molecules, novel methods to overcome this barrier function have been described. There are chemical, biochemical and physical methods, many of which are pain-free and therefore especially suitable for children. Also for adults non-invasive methods of vaccination and immunotherapy are attractive as self-administration is feasible. Future products are currently undergoing clinical tests which provide promising results. PMID:25305116

  2. Novel immunotherapies for the treatment of melanoma.

    PubMed

    Gato-Cañas, Maria; Arasanz, Hugo; Blanco-Luquin, Idoia; Glaría, Estíbaliz; Arteta-Sanchez, Virginia; Kochan, Grazyna; Escors, David

    2016-05-01

    Immunotherapies are achieving clinical success for the treatment of many cancers. However, it has taken a long time to exploit the potential of the immune system for the treatment of human cancers. We cannot forget that this has been the consequence of very extensive work in basic research in preclinical models and in human patients. Thus, it is rather hard to compile all of it while giving a comprehensive view on this subject. Here we have attempted to give an overall perspective in immunotherapy of melanoma. A brief overview on current therapies is provided, followed by adoptive cell therapies. Gene engineering strategies to improve these therapies are also explained, finishing with therapies based on interference with immune checkpoint pathways. PMID:27140413

  3. Prospects for immunotherapy and vaccines against Cryptosporidium

    PubMed Central

    Mead, Jan R

    2014-01-01

    Cryptosporidium spp is a ubiquitous parasite that has long been recognized as a frequent cause of protozoal diarrhea in humans. While infections in immunocompetent hosts are usually self-limiting, immunocompromised individuals can develop severe, chronic, and life-threatening illness. Vaccine development or immunotherapy that prevents disease or reduces the severity of infection is a relevant option since efficacious drug treatments are lacking. In particular, children in developing countries might benefit the most from a vaccine since cryptosporidiosis in early childhood has been reported to be associated with subsequent impairment in growth, physical fitness, and intellectual capacity. In this review, immunotherapies that have been used clinically are described as well as experimental vaccines and their evaluation in vivo. PMID:24638018

  4. Strategies and developments of immunotherapies in osteosarcoma

    PubMed Central

    WAN, JIA; ZHANG, XIANGHONG; LIU, TANG; ZHANG, XIANGSHENG

    2016-01-01

    Osteosarcoma (OS) is a frequently observed primary malignant tumor. Current therapy for osteosarcoma consists of comprehensive treatment. The long-term survival rate of patients exhibiting nonmetastatic OS varies between 65–70%. However, a number of OS cases have been observed to be resistant to currently used therapies, leading to disease recurrence and lung metastases, which are the primary reasons leading to patient mortality. In the present review, a number of pieces of evidence provide support for the potential uses of immunotherapy, including immunomodulation and vaccine therapy, for the eradication of tumors via upregulation of the immune response. Adoptive T-cell therapy and oncolytic virotherapy have been used to treat OS and resulted in objective responses. Immunologic checkpoint blockade and targeted therapy are also potentially promising therapeutic tools. Immunotherapy demonstrates significant promise with regard to improving the outcomes for patients exhibiting OS. PMID:26834853

  5. Evolving Immunotherapy Strategies in Urothelial Cancer

    PubMed Central

    Brancato, Sam J.; Lewi, Keidren; Agarwal, Piyush K.

    2016-01-01

    The treatment of nonmuscle-invasive urothelial carcinoma with bacillus Calmette-Guérin (BCG) represents the importance of immunotherapy in the treatment of cancer. Despite its clinical efficacy, up to 30% of patients will ultimately experience progression to muscle-invasive disease. This, along with an improved understanding of the biologic pathways involved, has led to efforts to improve, enhance, or alter the immune response in the treatment of urothelial carcinoma. A number of novel therapeutic approaches currently are being pursued, including recombinant BCG to induce T helper type 1 (Th1) immune responses, nonlive Mycobacterium agents, targeted agents toward cancer-associated antigens, immune-modulating vaccines, and adoptive T-cell therapies. Here, we review the current and future immunotherapy treatment options for patients with urothelial cancer. PMID:25993187

  6. Coinhibitory Pathways in Immunotherapy for Cancer.

    PubMed

    Baumeister, Susanne H; Freeman, Gordon J; Dranoff, Glenn; Sharpe, Arlene H

    2016-05-20

    The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer. PMID:26927206

  7. Adoptive T Cell Immunotherapy for Cancer

    PubMed Central

    Perica, Karlo; Varela, Juan Carlos; Oelke, Mathias; Schneck, Jonathan

    2015-01-01

    Harnessing the immune system to recognize and destroy tumor cells has been the central goal of anti-cancer immunotherapy. In recent years, there has been an increased interest in optimizing this technology in order to make it a clinically feasible treatment. One of the main treatment modalities within cancer immunotherapy has been adoptive T cell therapy (ACT). Using this approach, tumor-specific cytotoxic T cells are infused into cancer patients with the goal of recognizing, targeting, and destroying tumor cells. In the current review, we revisit some of the major successes of ACT, the major hurdles that have been overcome to optimize ACT, the remaining challenges, and future approaches to make ACT widely available. PMID:25717386

  8. Optimization of surface morphology and scattering properties of TCO/AIT textured glass front electrode for thin film solar cells

    NASA Astrophysics Data System (ADS)

    Addonizio, M. L.; Fusco, L.; Antonaia, A.; Cominale, F.; Usatii, I.

    2015-12-01

    Aluminium induced texture (AIT) method has been used for obtaining highly textured glass substrate suitable for silicon based thin film solar cell technology. Wet etch step parameters of AIT process have been varied and effect of different etchants and different etching times on morphological and optical properties has been analyzed. The resulting morphology features (shape, size distribution, inclination angle) have been optimized in order to obtain the best scattering properties. ZnO:Ga (GZO) films have been deposited by sputtering technique on AIT-processed glass. Two different ZnO surface morphologies have been obtained, strongly depending on the underlying glass substrate morphology induced by different etching times. Very rough and porous texture (σrms ∼ 150 nm) was obtained on glass etched 2 min showing cauliflower-like structure, whereas a softer texture (σrms ∼ 78 nm) was obtained on glass etched 7 min giving wider and smoother U-shaped craters. The effect of different glass textures on optical confinement has been tested in amorphous silicon based p-i-n devices. Devices fabricated on GZO/high textured glass showed a quantum efficiency enhancement due to both an effective light trapping phenomenon and an effective anti-reflective optical behaviour. Short etching time produce smaller cavities (<1 μm) with deep U-shape characterized by high roughness, high inclination angle and low autocorrelation length. This surface morphology promoted a large light scattering phenomenon, as evidenced by haze value and by angular resolved scattering (ARS) behaviour, into a large range of diffraction angles, giving high probability of effective light trapping inside a PV device.

  9. Industrial Fungal Enzymes: An Occupational Allergen Perspective

    PubMed Central

    Green, Brett J.; Beezhold, Donald H.

    2011-01-01

    Occupational exposure to high-molecular-weight allergens is a risk factor for the development and pathogenesis of IgE-mediated respiratory disease. In some occupational environments, workers are at an increased risk of exposure to fungal enzymes used in industrial production. Fungal enzymes have been associated with adverse health effects in the work place, in particular in baking occupations. Exposure-response relationships have been demonstrated, and atopic workers directly handling fungal enzymes are at an increased risk for IgE-mediated disease and occupational asthma. The utilization of new and emerging fungal enzymes in industrial production will present new occupational exposures. The production of antibody-based immunoassays is necessary for the assessment of occupational exposure and the development of threshold limit values. Allergen avoidance strategies including personal protective equipment, engineering controls, protein encapsulation, and reduction of airborne enzyme concentrations are required to mitigate occupational exposure to fungal enzymes. PMID:21747869

  10. Interfaces Between Allergen Structure and Diagnosis: Know Your Epitopes

    PubMed Central

    Pomés, Anna; Chruszcz, Maksymilian; Gustchina, Alla; Wlodawer, Alexander

    2016-01-01

    Allergy diagnosis is based on the patient’s clinical history and can be strengthened by tests that confirm the origin of sensitization. In the past 25 years, these tests have evolved from the exclusive in vivo or in vitro use of allergen extracts, to complementary molecular-based diagnostics that rely on in vitro measurements of IgE reactivity to individual allergens. For this to occur, an increase in our understanding of the molecular structure of allergens, largely due to the development of technologies such as molecular cloning and expression of recombinant allergens, X-ray crystallography, or nuclear magnetic resonance (NMR), has been essential. New in vitro microarray or multiplex systems are now available to measure IgE against a selected panel of purified natural or recombinant allergens. The determination of the three-dimensional structure of allergens has facilitated detailed molecular studies, including the analysis of antigenic determinants for diagnostic purposes. PMID:25750181

  11. New Trends in Food Allergens Detection: Toward Biosensing Strategies.

    PubMed

    Alves, Rita C; Barroso, M Fátima; González-García, María Begoña; Oliveira, M Beatriz P P; Delerue-Matos, Cristina

    2016-10-25

    Food allergens are a real threat to sensitized individuals. Although food labeling is crucial to provide information to consumers with food allergies, accidental exposure to allergenic proteins may result from undeclared allergenic substances by means of food adulteration, fraud or uncontrolled cross-contamination. Allergens detection in foodstuffs can be a very hard task, due to their presence usually in trace amounts, together with the natural interference of the matrix. Methods for allergens analysis can be mainly divided in two large groups: the immunological assays and the DNA-based ones. Mass spectrometry has also been used as a confirmatory tool. Recently, biosensors appeared as innovative, sensitive, selective, environmentally friendly, cheaper and fast techniques (especially when automated and/or miniaturized), able to effectively replace the classical methodologies. In this review, we present the advances in the field of food allergens detection toward the biosensing strategies and discuss the challenges and future perspectives of this technology. PMID:25779935

  12. Prostate cancer immunotherapy: beyond immunity to curability.

    PubMed

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  13. ATMPs for Cancer Immunotherapy: A Regulatory Overview.

    PubMed

    Galli, Maria Cristina

    2016-01-01

    This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described. PMID:27033211

  14. Update on the challenges and recent advances in cancer immunotherapy

    PubMed Central

    Baronzio, Gianfranco; Parmar, Gurdev; Shubina, Irina ZH; Cassutti, Valter; Giuli, Sergio; Ballerini, Marco; Kiselevsky, Mikhail

    2013-01-01

    This overview provides an analysis of some of the immunotherapies currently in use and under investigation, with a special focus on the tumor microenvironment, which we believe is a major factor responsible for the general failure of immunotherapy to date. It is our expectation that combining immunotherapy with methods of altering the tumor microenvironment and targeting regulatory T cells and myeloid cells will yield favorable results.

  15. Cancer Immunotherapy for Gliomas: Overview and Future Directions.

    PubMed

    Hashimoto, Naoya

    2016-07-15

    Immunotherapy has been highlighted because we have obtained much evidence, which includes theoretical backborn as well as favorable results from clinical trials. As immunotherapy gives an apparently different cytotoxic mechanism and a little adverse event, the promising results are getting a lot of attention. In this article, cancer immunotherapy for gliomas is reviewed thoroughly from the literature, focusing on the clinical trial results. PMID:27087194

  16. Cancer Immunotherapy for Gliomas: Overview and Future Directions

    PubMed Central

    HASHIMOTO, Naoya

    2016-01-01

    Immunotherapy has been highlighted because we have obtained much evidence, which includes theoretical backborn as well as favorable results from clinical trials. As immunotherapy gives an apparently different cytotoxic mechanism and a little adverse event, the promising results are getting a lot of attention. In this article, cancer immunotherapy for gliomas is reviewed thoroughly from the literature, focusing on the clinical trial results. PMID:27087194

  17. Immunotherapy for nasopharyngeal cancer-a review.

    PubMed

    Jain, Amit; Chia, Whay Kuang; Toh, Han Chong

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV) and characterized by peritumoral immune infiltrate. Advanced NPC has high lethality. Immunotherapy directed against EBV antigen targets has been previously explored in clinical trials, and is likely to be validated as an important target in NPC as randomized data emerges in the future. Cancer vaccines and adoptive T cell therapy have been explored in the clinic, with the latter showing the greatest success. Recent advances in gene sequencing technology now allow personalized tumor epitope mapping, whilst the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis offers the opportunity to activate adaptive T cell response in vivo. Anti-PD1 antibodies have shown promising activity in early phase clinical trials, and randomized studies against chemotherapy are underway. As immunotherapy is incorporated into standard treatment paradigms, issues of optimal combinations with targeting agents, immune adjuvants, and sequence with chemotherapy and radiation therapy will need to be addressed. Effective strategies to increase tumor antigenicity, improve immunological memory and reduce immune escape, will need to be developed to improve treatment outcomes. Here we present a brief history of the evolution of immunotherapy in NPC, and highlight key concepts relevant to its further development in the clinic. PMID:27121882