Philadelphia Autoimmunity Center of Excellence

描述（由申请人提供）：这是一份在费城建立卓越自身免疫中心（ACE）的提案。四家领先的机构正在联手创建一个ACE，从实验室到临床研究自身免疫。来自托马斯·杰斐逊大学、坦普尔大学、宾夕法尼亚大学和费城儿童医院的研究人员将参与这次ACE的各个方面。这些机构结合了强大的免疫学科学基础和长期以来在各种自身免疫性疾病患者管理方面的卓越表现，使费城成为建立该中心的理想场所。费城ACE提出了2个临床试验概念，2个基础科学项目和1个试点项目。临床试验的概念是：1)在硬皮病患者中进行一种新型治疗性抗体的I期试验，该抗体可以阻断LFA-1；2)一种口服、大豆衍生的天然蛋白酶抑制剂，Bowman-Birk抑制剂浓缩物，用于多发性硬化症的I期试验。研究内容包括3个项目：1)研究最近发现的人类Th17细胞及其在多发性硬化症中的调节作用；2)翻译酪氨酸激酶mer家族在小鼠系统性红斑狼疮自身免疫中的重要性；3)建立造血人源化NOG小鼠模型的试点项目。该模型将成为研究人类自身免疫性疾病的宝贵工具。中心设有2个核心：A)流式细胞术/细胞分选核心，用于集中项目所需的FACS分析；B)行政核心，负责管理中心，促进参与不同项目的临床医生和基础科学家之间的互动。

DESCRIPTION (provided by applicant): This is a proposal to establish an Autoimmunity Center of Excellence (ACE) in Philadelphia. Four leading institutions are joining forces to create an ACE, to study autoimmunity from bench to bedside. Investigators from Thomas Jefferson University, Temple University, University of Pennsylvania and Children's Hospital of Philadelphia will participate in various aspects of this ACE. These institutions combine strong scientific bases in immunology with longstanding excellence in the management of patients with various autoimmune disorders, making Philadelphia an ideal place for establishing this Center. The Philadelphia ACE proposes 2 clinical trial concepts, 2 basic science projects and one pilot project. The clinical trial concepts are: 1) a phase I trial of a novel therapeutic antibody, which blocks LFA-1, in patients with scleroderma; and 2) a phase I trial of an oral, soy-derived, natural protease inhibitor, Bowman-Birk Inhibitor Concentrate, in multiple sclerosis. The research component consists of 3 projects: 1) investigation of the recently discovered Th17 cells in humans and their regulation in multiple sclerosis, 2) translation of recent findings on the importance of the mer family of tyrosine kinases in murine autoimmunity to systemic lupus erythematosus; and 3) a pilot project to develop a hematopoietically humanized NOG mouse model. This model will be an invaluable tool to study human autoimmune diseases. The Center has 2 cores: A) flow cytometry/cell sorting core, to centralize the FACS analyses required in the projects; and B) administrative core, for administration of the Center and facilitating interaction between clinicians and basic scientists involved in the different projects. Autoimmune diseases have considerable negative impact on public health. The proposed ACE will investigate fundamental mechanisms of autoimmunity. Further, the ACE proposes to conduct trials of two therapeutic agents for treatment of patients with autoimmune diseases. Thus, the proposed ACE will be a valuable and relevant asset in the pursuit of improved public health. CLINICAL COMPONENT (Jimenez, S) CLINICAL COMPONENT DESCRIPTION (provided by applicant): The clinical component of the Philadelphia ACE brings together clinician-investigators, physician-scientists and basic scientists from four Philadelphia institutions to perform clinical trials of new and promising agents for the treatment of various autoimmune disorders. Clinician-investigators with expertise and experience in clinical trials are proposing clinical trial concepts. Physician-scientists and basic scientists familiar with the diseases will collaborate with clinicians in endeavoring to understand the basic mechanisms of action of these new agents and, in the process, to better understand the disease itself. All four institutions are interested and willing to submit clinical trial concepts to the Steering Committee of the ACE. Initially, the Center will focus on the following two clinical trial concepts: 1) Phase I trial of a novel therapeutic agent, which blocks LFA-1, in patients with scleroderma; 2) Phase I trial of an oral, soy-derived natural protease inhibitor, Bowman-Birk Inhibitor Concentrate, in multiple sclerosis. The participating institutions have outstanding infrastructure and the expertise to perform first-class clinical trials. Details on institutional resources, on clinics specialized in several autoimmune disorders and the potential to recruit patients for other ACEs are given in this section. The Clinical Component proposes novel clinical trial concepts and studies to understand the mechanisms of action of the therapeutics being tested. As such, they are an integral part of this ACE.