Immunotherapeutic Modulation of Peanut Allergy

花生过敏的免疫治疗调节

• 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
• 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

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.

花生过敏是常见的，最近的研究估计儿童的患病率为0.8%，一般人群的总患病率为0.5% - 1%，有证据表明花生过敏的患病率在美国和欧洲都在上升。目前，花生过敏症的唯一治疗方法是无花生饮食和随时可获得自我注射肾上腺素。然而，意外摄入是常见的，高达50%的食物过敏患者在两年的时间内发生过敏反应。对花生的过敏反应可能是严重的并危及生命，花生和/或树坚果过敏占致命的食物引起的过敏反应的绝大多数。鉴于这些事实，开发有效的花生过敏疗法至关重要。在过去的几年里，我们在对花生过敏的理解以及花生和其他食物过敏的潜在治疗策略方面取得了实质性进展。 最近的研究表明，口服免疫疗法治疗牛奶，鸡蛋和花生过敏的潜力，但这种疗法主要是诱导脱敏，不良反应是常见的，不可预测的，有时严重。因此，需要更有效的治疗方法。 本申请的目的是在这些初步研究的基础上进行扩展，以确定哪种治疗方式可能最有效，并可能适用于花生过敏患者的一般人群，并了解与这些免疫调节剂诱导的“脱敏”和“耐受性”发展相关的免疫机制。我们将通过以下方式实现这一目标： 具体目标如下：（1）对正在进行的花生舌下免疫治疗试验进行补充 （2）实施新型治疗化合物EMP-123的I/II期试验， 基于我们正在进行的CoFAR 1 I期试验的结果;（3）启动一项新的表皮 免疫疗法（EPIT）用于治疗花生过敏;（4）调查相似性和差异 这些方法之间通过使用新的机制研究。在这三项治疗试验中，我们将 研究这些疗法的临床和免疫学效果，确定它们诱导长期免疫缺陷的潜力。 耐受性，并评估其安全性。通过将花生过敏原引入免疫系统， 不同的途径，即口腔粘膜，表皮和直肠粘膜[与先天免疫激活剂]，我们 预期不同的宿主反应，将诱导脱敏和最终耐受。机制 计划中的研究将为IgE介导的食物过敏耐受性的诱导提供新的见解。