Autoimmunity Center of Excellence Clinical Research Program

描述(申请人提供)：本申请集中于使用体外扩增的自体调节性T细胞(TRGs)治疗自身免疫性疾病的可能性。中心主题是Tregs提供了针对自身免疫的重要保护。基于这一主题，中心假设是Treg疗法可能是治疗各种自身免疫性疾病的安全有效的方法。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疗法在抗原非特异性自身免疫性疾病(系统性红斑狼疮)(SLE)中的作用，另一个项目将研究Treg疗法在抗原特异性自身免疫性疾病(寻常型天疱疮)(PV)中的作用。选择这两种疾病为我们提供了以下重要机会：(1)检查这种治疗方法是否普遍适用于 目的：(I)比较抗原特异性和非抗原特异性自身免疫性疾病的安全性、有效性和作用机制；(Iii)比较多克隆和抗原特异性Treg疗法在相同疾病(PV)中的疗效；(Iv)在狼疮和PV疾病中检查相同的靶组织(皮肤)。具体目标是：主要项目-实施L-II阶段开发计划，旨在测试Treg疗法在狼疮皮肤表现患者中的可行性、安全性和潜在疗效。替代项目-实施L-11期开发计划，旨在比较自体多克隆和浓缩抗原特异性Treg疗法在PV患者中的应用。通过这些项目，我们的目标是证明转移的Tregs在血液和目标组织中的存在和持久性；进行T细胞受体测序以确定输入的Tregs是否增殖；评估血液和皮肤中的生物标记物；并产生疗效数据，为最终的关键试验奠定基础。 相关性：加州大学旧金山分校ACE计划的广泛目标是与其他ACE站点合作，将免疫学和分子生物学方面的进展转化为对自身免疫性疾病患者的实用、安全和有效的治疗。在这一框架内，加州大学旧金山分校的网站将重点研究使用自体调节性T细胞作为治疗自身免疫性疾病的新方法的前景。通过这样做，我们将检查一种可能对各种自身免疫性疾病具有广泛适用性的方法。

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.