Developmental Immunotherapeutics For Allergic Diseases A

该项目旨在开发治疗过敏性疾病的新的免疫疗法，以及了解其作用机制和合理应用所需的实验室技术。我们目前正在进行一项临床试验，通过监测过敏原特异性T细胞反应来检测过敏原免疫治疗的免疫学效果。这项工作的假设是过敏原免疫治疗通过耐受性(过敏原特异性T细胞的减少)起作用，而不是通过Th2到Th1的转变。了解变应原免疫治疗的免疫学机制是开发新的更有效的抗原特异性治疗方法的必要条件。嗜酸性胃肠炎是一种严重的肠道炎症性疾病，以致密的组织嗜酸性粒细胞浸润为特征，常与特应性和食物过敏有关。在这些食物过敏对象中，嗜酸性胃肠炎似乎是食物过敏的一种严重表现，因此，提供了一个模型系统来研究与食物过敏发病机制有关的问题。为了研究IL-5在嗜酸性胃肠炎和食物过敏中的作用，我们使用人源化的抗IL-5的单抗SCH55700进行了临床试验。中期结果显示，单剂SCH55700在48小时内使外周血嗜酸性粒细胞数量迅速下降80%，一个月后4名受试者中有3名患者的胃肠道嗜酸性粒细胞下降了50%-70%。这些数据表明，在EG中发现的外周血和组织中的嗜酸性粒细胞对IL-5阻断都有反应。

This project seeks to develop novel immunologic therapies for allergic diseases as well as the laboratory techniques required to understand their mechanisms of action and rational application. We are presently performing a clinical trial examining the immunological effects of allergen immunotherapy by monitoring allergen specific T cell responses. The hypothesis of this work is that allergen immunotherapy works via tolerance (a decrease in allergen specific T cells) rather than via a Th2 to Th1 shift. Understanding the immunological mechanisms of allergen immunotherapy is a requisite for developing new more effective antigen specific therapies. Eosinophilic gastroenteritis is a severe inflammatory disease of the gut, characterized by dense tissue eosinophil infiltration and is often associated with atopy and food allergy. In these food allergic subjects, eosinophilic gastroenteritis appears to be a severe manifestation of food allergy and as such, provides a model system in which to examine questions relating to the pathogenesis of food allergy. To examine the role of IL-5 in subjects with eosinophilic gastroenteritis and food allergy, we are engaged in a clinical trial using SCH55700, a humanized anti-IL-5 monoclonal antibody. Interim results demonstrate that a single dose of SCH55700 yielded a rapid 80% drop in peripheral blood eosinophil counts within 48 hours and that after one month gastrointestinal eosinophils were decreased by 50-70% in 3 of 4 subjects. These data demonstrate that both the peripheral blood and tissue eosinophilia found in EG are responsive to IL-5 blockade.