Philadelphia Autoimmunity Center of Excellence

描述（由申请人提供）：这是一项在费城建立自身免疫卓越中心（ACE）的提案。四个领先的机构正在联手创建ACE，从实验室到床边研究自身免疫。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调查人员将参与这一ACE的各个方面。这些联合收割机结合了免疫学的强大科学基础和各种自身免疫性疾病患者的长期卓越管理，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个基础科学项目和一个试点项目。临床试验概念是：1）一种新型治疗性抗体的I期试验，该抗体在硬皮病患者中阻断LFA-1; 2）一种口服大豆衍生的天然蛋白酶抑制剂Bowman-Birk抑制剂浓缩物在多发性硬化症中的I期试验。研究部分由3个项目组成：1）研究最近发现的人类Th 17细胞及其在多发性硬化症中的调节，2）翻译最近关于酪氨酸激酶mer家族在系统性红斑狼疮小鼠自身免疫中的重要性的研究结果;和3）开发造血人源化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。该中心有两个核心：A）流式细胞术/细胞分选核心，集中项目所需的FACS分析;和B）行政核心，用于中心的管理，并促进参与不同项目的临床医生和基础科学家之间的互动。 自身免疫性疾病对公共卫生有相当大的负面影响。拟议的ACE将研究自身免疫的基本机制。此外，ACE建议进行两种治疗药物的试验，用于治疗自身免疫性疾病患者。因此，拟议的环境谘询委员会将是一项宝贵和相关的资产，以寻求改善公众健康。 临床组件（Jimenez，S） 临床组成部分描述（由申请人提供）：费城ACE的临床组成部分汇集了来自费城四家机构的临床研究人员、医生-科学家和基础科学家，对治疗各种自身免疫性疾病的新型和有前途的药物进行临床试验。具有临床试验专业知识和经验的临床研究者正在提出临床试验概念。熟悉这些疾病的物理科学家和基础科学家将与临床医生合作，努力了解这些新药物的基本作用机制，并在此过程中更好地了解疾病本身。所有四个机构都有兴趣并愿意向ACE指导委员会提交临床试验概念。最初，该中心将专注于以下两个临床试验概念：1）在硬皮病患者中阻断LFA-1的新型治疗剂的I期试验; 2）口服大豆衍生的天然蛋白酶抑制剂Bowman-Birk Inhibitor Concentrate在多发性硬化症中的I期试验。参与机构拥有出色的基础设施和专业知识，可以进行一流的临床试验。本节详细介绍了机构资源、几种自身免疫性疾病的专科诊所以及招募其他ACE患者的可能性。 临床部分提出了新的临床试验概念和研究，以了解正在测试的治疗药物的作用机制。因此，它们是ACE的组成部分。

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.