Immunotherapeutic Modulation of Peanut Allergy

花生过敏的免疫治疗调节

基本信息

批准号：
9305647
负责人：
ROBERT A WOOD
金额：
$ 134.48万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-11 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9305647
关键词：
Accident and Emergency department Accounting Adult Adverse reactions Affect Aftercare Allergens Allergic Allergic Reaction Allergy to eggs Allergy to peanuts American Anaphylaxis Basophils Binding Biological Assay Child Clinical Development Diet Down-Regulation Epidermis Epinephrine Epitopes Europe Food Food Hypersensitivity France General Population Goals IgE Immune Immune Tolerance Immune response Immune system Immunobiology Immunologics Immunotherapeutic agent Immunotherapy Ingestion Injectable Label Lead Life Mediating Milk Hypersensitivity Modality Mucous Membrane Nut Hypersensitivity Oral mucous membrane structure Outcome Patients Pattern Phase Population Prevalence Route Safety T-Lymphocyte Treatment Protocols United Kingdom United States base clinical effect desensitization effective therapy insight novel novel therapeutics oral immunotherapy phase I trial rectal response sublingual immunotherapy treatment strategy

项目摘要

Peanut allergy is common, with recent studies estimating a prevalence of 0.8% in children and an overall prevalence of 0.5% - 1% in the general population, and there is evidence that the prevalence of peanut allergy is rising in both the United States and Europe. Currently, the only treatment for peanut allergy is a peanut-free diet and ready access to self-injectable epinephrine. However, accidental ingestions are common, with up to 50% of food-allergic patients having an allergic reaction over a two-year period. Allergic reactions to peanut can be severe and life threatening, with peanut and/or tree nut allergies accounting for the vast majority of fatal food-induced anaphylaxis. Given these facts, the development of effective therapy for peanut allergy is critical. Over the past several years we have made substantial progress in our understanding of peanut allergy and potential treatment strategies for peanut and other food allergies. Recent studies have shown the potential of oral immunotherapy for the treatment of milk, egg and peanut allergies, but this therapy primarily appears to induce desensitization, and adverse reactions are common, unpredictable and sometimes severe. Consequently, more effective therapies are needed. The goal of this application is to expand upon these preliminary studies to determine which treatment modality is likely to be most effective and potentially applicable to the general population of peanut allergic patients, and to understand the immunologic mechanisms associated with the development of "desensitization" and "tolerance" induced by these immunotherapeutic modalifies. We will accomplish this by pursuing the following Specific Aims: (1) confinue the ongoing trial of peanut sublingual immunotherapy (SLIT) initiated in CoFAR 1; (2) implement a Phase l/ll trial of a novel therapeufic compound, EMP-123, based on the results of our ongoing Phase I trial in CoFAR 1; (3) initiate a trial of a novel epicutaneous immunotherapy (EPIT) for the treatment of peanut allergy; and (4) invesfigate the similarities and differences between these approaches through the use of novel mechanisfic studies. In the 3 therapeufic trials, we will study the clinical and immunologic effects of these therapies, determine their potenfial to induce long-term tolerance, and assess their safety profiles. By introducing peanut allergens to the immune system by different routes, i.e. oral mucosa, epidermis, and rectal mucosa [with innate immune activators], we anticipate different host responses that will induce desensitizafion and eventually tolerance. The mechanisfic studies planned should provide new insight into the inducfion of tolerance in IgE-mediated food allergy.

花生过敏很常见，最近的研究估计儿童患病率为0.8％，总人群的总体患病率为0.5％ - 1％，并且有证据表明，在美国和欧洲，花生过敏的患病率正在上升。目前，花生过敏的唯一治疗方法是无花生饮食，并可以随时获得自我注射的肾上腺素。但是，意外摄入很常见，多达50％的食物过敏患者在两年内有过敏反应。对花生的过敏反应可能是严重的，威胁生命，花生和/或树坚果过敏，这是绝大多数致命食品引起的过敏反应的原因。鉴于这些事实，对花生过敏的有效疗法的发展至关重要。在过去的几年中，我们在对花生过敏和花生和其他食物过敏的花生过敏和潜在治疗策略方面取得了重大进展。最近的研究表明，口服免疫疗法对牛奶，鸡蛋和花生过敏的治疗有潜力，但是这种疗法似乎主要诱导脱敏，不良反应是常见的，不可预测的，有时是严重的。因此，需要更有效的疗法。该应用的目的是扩展这些初步研究，以确定哪种治疗方式可能最有效，并且有可能适用于花生过敏患者的一般人群，并了解与这些免疫治疗方法引起的“脱敏”和“耐受性”相关的免疫学机制。我们将通过追求以下具体目的：（1）巩固正在进行的花生舌下免疫疗法的试验（SLIT）在Cofar 1中启动；（2）实施一种新型治疗化合物EMP-123的L/LL试验根据我们在Cofar 1中正在进行的I期试验的结果；（3）启动一种新型的表皮试验免疫疗法（EPIT）用于治疗花生过敏；（4）提出相似性和差异通过使用新型机械性研究，这些方法之间的方法。在三个治疗试验中，我们将研究这些疗法的临床和免疫学作用，确定它们的能力以诱导长期容忍并评估其安全概况。通过将花生过敏原引入免疫系统不同的路线，即口腔粘膜，表皮和直肠粘膜[带有先天免疫激活剂]，我们预期会引起脱感抑制并最终耐受性的不同宿主反应。机械性计划的研究应提供有关IgE介导的食物过敏的耐受性的新见解。