Developmental Immunotherapeutics for Allergic Diseases and Asthma

该项目旨在开发用于过敏性疾病的新型免疫疗法，以及了解其作用机制和合理应用所需的实验室技术。我们已经开发了使用流式细胞术和真实的时间定量PCR来评估过敏原特异性T细胞应答的方法，其灵敏度在此之前是不可能的。我们最近完成了可溶性IL-4受体作为哮喘抗炎/Th 2耐受原性治疗的II期研究，并正在分析结果。我们已经开发了一种体外模型来检查使用共刺激阻断剂如CTLA-4 IG和抗B7诱导过敏原特异性耐受。该模型允许临床前评估用于治疗性诱导对过敏原的免疫耐受的潜在策略。我们将类似的方法应用于小鼠疫苗模型，以了解DNA疫苗如何产生特异性免疫反应。我们已经表明，DNA疫苗的持久免疫应答是由于DNA中的免疫刺激序列诱导的持续性IL-12。此外，我们已经确定了一个新的作用，CD 8细胞在提供IFN-γ介导的“帮助”，以Th 1细胞的DNA疫苗接种的背景下。

This project seeks to develop novel immunologic therapies for allergic diseases as well as the laboratory techniques required to understand their mechanism of action and rational application. We have developed the means, using both flow cytometry and real time quantitative PCR to evaluate allergen specific T cell responses with a sensitivity heretofore not possible. We have recently completed a phase II study of soluble IL-4 receptor as an anti-inflammatory/Th2 tolerogenic therapy for asthma and are in the process of analyzing the results. We have developed an in vitro model to examine the induction of allergen specific tolerance using costimulatory blockers such as CTLA-4 Ig and anti-B7. This model allows the pre-clinical evaluation of potential strategies for the therapeutic induction of immunological tolerance to allergens. We have applied a similar approach to mouse vaccine models to understand how DNA vaccines generate specific immune responses. We have shown that the long lasting immune response to DNA vaccines is due to persistent IL-12 induced by immunostimulatory sequences in the DNA. Additionally, we have identified a novel role for CD8 cells in providing IFN-gamma mediated "help" to Th1 cells in the context of DNA vaccination.