Immune Tolerance Network

描述(由申请人提供)：随着基础免疫学最近的重大进展，临床利用这一认识的机会已经扩大，我们对人类免疫机制进行直接评估的能力也有所扩大。这是免疫耐受网络(ITN)方法的基石--对新的耐受疗法进行临床评估，同时评估疾病的细胞、遗传和免疫学机制以及它们如何因治疗而改变。在这一更新申请中，我们描述了我们提出的科学和操作框架，使ITN能够成功地加速移植、自身免疫和过敏耐受治疗的发展。我们将概述将我们当前的战略演变为下一代计划试验的过程，以及我们计划如何运营一个灵活的、着眼于未来的组织，准备领导和采用目前未知的未来创新。我们提出了一个包括数百名研究人员、顾问和临床站点的协作结构 与ITN工作人员的核心团队合作，运营一个在科学和财务上都有效的项目。ITN最近通过的几项新创新将鼓励学术研究人员的广泛参与，包括扩大资源共享和数据共享业务。三个主要机构--弗吉尼亚州梅森的贝纳罗亚研究所、马萨诸塞州总医院和加州大学旧金山分校--构成了这项申请的管理骨干，另有20个机构担任领导和主要顾问角色。 相关性：拟议的免疫耐受网络(ITN)赠款解决了主要的未得到满足的卫生需求。在美国，5%的人患有自身免疫性疾病，另外15%的人患有过敏性疾病。移植是一种挽救生命的器官衰竭干预措施，但它伴随着巨大的负担和风险，在每个领域，临床前研究表明，对于许多受影响的个体来说，免疫耐受应该是一种可以实现的治疗前景。成功的耐受提供了长期摆脱免疫抑制治疗的可能性，在生活质量、疾病负担和医疗费用方面带来了根本性的改善。

DESCRIPTION (provided by applicant): In parallel with major recent advances in basic immunology, opportunities for clinical exploitation of this understanding have broadened, as has our ability to perform direct assessment of immunological mechanisms in humans. This is a cornerstone of the Immune Tolerance Network (ITN) approach - clinical assessment of novel tolerance therapeutics, while simultaneously evaluating the cellular, genetic and immunologic mechanisms of disease and how they are altered in response to therapy. In this renewal application, we describe the scientific and operational framework that we propose to enable the ITN to successfully accelerate the development of tolerance therapies in transplantation, autoimmunity, and allergy. We will outline a process to evolve our current strategies into the next generation of planned trials, as well as how we plan to operate a nimble, future-focused organization, poised to lead and adopt future innovations that are currently unknown. We propose a collaborative structure involving hundreds of investigators, advisors, and clinical sites working in tandem with a core group of ITN staff, operating a program that is both scientifically and financially efficient. Several new innovations recently adopted by the ITN will encourage widespread involvement from academic investigators, including expanded resource sharing and data sharing operations. Three major institutions, the Benaroya Research Institute at Virginia Mason, Massachusetts General Hospital, and the University of California, San Francisco, form the administrative backbone for this application, with another twenty institutions represented in leadership and major advisory roles. RELEVANCE: The proposed Immune Tolerance Network (ITN) grant addresses major unmet health needs. In the United States, autoimmune diseases affect >5% of the population, and allergic diseases affect another ~15%. Transplantation is a life-saving intervention for organ failure, but it comes with a significant burden and risk, in each area, pre-clinical studies show that immune tolerance should be an achievable therapeutic prospect for many affected individuals. Successful tolerance offers the possibility of long-term freedom from immunosuppressive therapy, bringing a radical improvement in terms of quality of life, disease burden, and health care cost.