Immunotherapeutic Modulation of Peanut Allergy

花生过敏很常见，最近的研究估计，儿童的患病率为0.8%，普通人群的总体患病率为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，花生过敏的唯一治疗方法是不含花生的饮食和随时可以自我注射的肾上腺素。然而，意外摄入是很常见的，高达50%的食物过敏患者在两年内出现过敏反应。对花生的过敏反应可能是严重的，并危及生命，花生和/或坚果过敏占致命食物过敏反应的绝大多数。鉴于这些事实，开发有效的花生过敏治疗方法是至关重要的。在过去的几年里，我们在理解花生过敏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，口服免疫疗法有可能治疗牛奶、鸡蛋和花生过敏，但这种疗法主要似乎会导致脱敏，不良反应很常见，不可预测，有时甚至很严重。因此，需要更有效的治疗方法。 本申请的目的是扩大这些初步研究，以确定哪种治疗方式可能最有效，并可能适用于普通花生过敏患者，并了解与这些免疫治疗方式诱导的“脱敏”和“耐受”发展相关的免疫学机制。我们将通过以下方式实现这一目标 追求以下具体目标：(1)限制正在进行的花生舌下免疫治疗试验 (Sit)在COFAR 1中启动；(2)实施新型治疗化合物EMP-123的L/11期试验， 基于我们正在进行的COFAR 1的第一阶段试验的结果；(3)启动一种新型皮肤上皮的试验 免疫疗法(EPIT)治疗花生过敏；以及(4)研究两者的异同 通过使用新的机制研究，在这些方法之间进行研究。在3个治疗试验中，我们将 研究这些疗法的临床和免疫学效果，确定它们的潜在诱导性。 耐受性，并评估其安全性。通过以下方式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[具有天然免疫激活剂]，我们 预期不同的宿主反应会导致脱敏并最终产生耐受性。该机制 计划中的研究应该为免疫球蛋白介导的食物过敏中耐受性的诱导提供新的见解。

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.