Philadelphia Autoimmunity Center of Excellence

描述(由申请人提供)：这是一项在费城建立自动免疫卓越中心(ACE)的建议。四家领先的机构正在联手创建ACE，从长凳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研究人员将参加这次ACE的各个方面。这些机构结合了强大的免疫学科学基础和在治疗各种自身免疫性疾病患者方面的长期卓越表现，使费城成为建立该中心的理想地点。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)一种新型的治疗性抗体的I期试验，它可以在硬皮病患者中阻断LFA-1；以及2)一种口服大豆衍生的天然蛋白酶抑制剂Bowman-Birk抑制剂浓缩物治疗多发性硬化症的I期试验。研究部分由3个项目组成：1)调查最近在人类中发现的Th17细胞及其在多发性硬化症中的调节；2)翻译关于酪氨酸激酶Mer家族在系统性红斑狼疮小鼠自身免疫中的重要性的最新发现；以及3)开发血液学人源化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无价工具。该中心有两个核心：A)流式细胞仪/细胞分选核心，用于集中项目所需的FACS分析；以及B)行政核心，用于管理中心，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众健康有相当大的负面影响。拟议的ACE将调查自身免疫的基本机制。此外，ACE建议对两种治疗自身免疫性疾病的药物进行试验。因此，拟议的ACE将是一项宝贵和相关的资产，有助于改善公众健康。 临床部分(希门尼斯、S) 临床成分描述(由申请人提供)：费城ACE的临床成分汇集了来自费城四所机构的临床研究人员、内科科学家和基础科学家，对治疗各种自身免疫性疾病的新的和有前途的药物进行临床试验。临床医生-在临床试验方面具有专业知识和经验的研究人员正在提出临床试验的概念。熟悉这种疾病的内科科学家和基础科学家将与临床医生合作，努力了解这些新制剂的基本作用机制，并在此过程中更好地了解疾病本身。所有四家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)一种新型治疗剂的第一阶段试验，它阻断LFA-1，用于硬皮病患者；2)一种口服大豆衍生的天然蛋白水解酶抑制剂，Bowman-Birk抑制剂浓缩物，用于多发性硬化症的第一阶段试验。参与机构拥有出色的基础设施和进行一流临床试验的专业知识。这一部分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为其他ACEs招募病人的可能性。 临床部分提出了新的临床试验概念和研究，以了解正在测试的疗法的作用机制。因此，它们是本次ACE不可分割的一部分。

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.