Autoimmunity Center of Excellence Clinical Research Program

描述（由申请人提供）：本申请的重点是利用体外扩增的自体调节性T细胞（Tregs）治疗自身免疫性疾病的潜力。中心主题是treg对自身免疫提供重要保护。基于这一主题，核心假设是Treg疗法可能是一种安全有效的治疗多种自身免疫性疾病的方法。为了解决这一假设，我们提出了两个互补的项目。一个项目将研究Treg治疗抗原非特异性自身免疫性疾病（系统性红斑狼疮）（SLE），另一个项目将研究Treg治疗抗原特异性自身免疫性疾病（寻常性天疱疮）（PV）。选择这两种疾病为我们提供了以下重要机会：(i)检查这种治疗方法是否普遍适用于所有疾病

DESCRIPTION (as provided by applicant): This application focuses on the potential for using ex vivo expanded autologous regulatory T cells (Tregs) in the treatment of autoimmune diseases. The central theme is that Tregs provide important protection against autoimmunity. Based on this theme, the central hypothesis is that Treg therapy may be a safe and effective approach to the treatment of diverse autoimmune diseases. To address this hypothesis, we propose two complementary projects. One project will examine Treg therapy in an antigen-non-specific autoimmune disease (systemic lupus erythematosus)(SLE), and one will examine Treg therapy in an antigen-specific autoimmune disease (pemphigus vulgaris)(PV). The selection of these two diseases affords us the following important opportunities: (i) to examine whether this therapeutic approach is generally applicable across clinically distinct autoimmune diseases; (ii) to compare safety, efficacy, and mechanism of action across both antigen-specific and antigen-non-specific autoimmune diseases; (iii) to compare polyclonal and antigen specific Treg therapy in the same disease (PV); and (iv) to examine the same target tissue (skin) in both lupus and PV disease. The specific aims are: Primary Project - Conduct a phase l-ll development program designed to test the feasibility, safety, and potential efficacy of Treg therapy in patients with cutaneous manifestations of lupus. Alternate Project - Conduct a phase l-ll development program designed to compare autologous polyclonal versus enriched antigen-specific Treg therapy in patients with PV. Through these projects, we aim to demonstrate the presence and persistence of transferred Tregs in blood and target tissue; perform T cell receptor sequencing to determine whether infused Tregs proliferate; assess biomarkers in blood and skin; and generate efficacy data to lay the foundation for eventual pivotal trials. RELEVANCE: The broad aim of the UCSF ACE program is to work collaboratively with other ACE sites to translate advances in immunology and molecular biology into practical, safe, and effective therapies for people with autoimmune diseases. Within this umbrella, the UCSF site will focus on examining the prospects of using autologous regulatory T cells as a novel approach to the treatment of autoimmune diseases. By so doing, we will be examining an approach that may have broad applicability across diverse autoimmune diseases.