Autoimmunity Center of Excellence Clinical Research Program

自身免疫卓越中心临床研究计划

• 批准号: 8680659
• 负责人: David Wofsy
• 金额: $ 544.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680659
• 关键词: Address; Affect; Antigens; Autoimmune Diseases; Autoimmunity; Autologous; Biological Markers; Blood; Clinical Research; Clinical Trials; Cutaneous; Data; Disease; Foundations; Goals; Grant; Immunologics; Immunology; Investigation; Lupus; Molecular Biology; Organ; Patients; Pemphigus Vulgaris; Phase; Program Development; Proliferating; Regulatory T-Lymphocyte; Safety; Site; Skin; Skin Tissue; Systemic Lupus Erythematosus; T-Cell Receptor; Testing; Therapeutic; Tissues; Translating; Work; base; design; effective therapy; novel; programs

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.

本申请集中于使用离体扩增的自体调节性T细胞（TCFs）在免疫治疗中的潜力。 自身免疫性疾病的治疗中心主题是，Teps提供重要的保护， 自身免疫基于这一主题，中心假设是Treg疗法可能是一种安全有效的治疗方法。 治疗各种自身免疫性疾病的方法。为了解决这个问题，我们提出两个假设。 补充项目。一个项目将研究Treg治疗在抗原非特异性自身免疫性 疾病（系统性红斑狼疮）（SLE），并且将在抗原特异性免疫应答中检查Treg疗法。 自身免疫性疾病（寻常天疱疮）（PV）。这两种疾病的选择为我们提供了以下信息 重要的机会：（一）检查这种治疗方法是否普遍适用于 临床上不同的自身免疫性疾病;（ii）比较两者的安全性、疗效和作用机制 抗原特异性和抗原非特异性自身免疫性疾病;（iii）比较多克隆和抗原特异性 Treg治疗相同疾病（PV）;和（iv）在两种疾病（PV）中检查相同的靶组织（皮肤）。 狼疮和PV疾病。具体目标是： 主要项目-进行一个阶段l-ll的开发计划，旨在测试可行性，安全性， Treg疗法在具有狼疮皮肤表现的患者中的潜在功效。 替代项目-进行旨在比较自体多克隆的第1 - 11期开发项目 与PV患者中的富集抗原特异性Treg治疗相比。 通过这些项目，我们的目标是证明血液中转移的THBE的存在和持久性。 进行T细胞受体测序以确定输注的T细胞是否增殖;评估 血液和皮肤中的生物标志物;并生成疗效数据，为最终的关键试验奠定基础。