Immune Tolerance Network

描述（由申请人提供）：随着最近基础免疫学的重大进展，临床利用这一认识的机会已经扩大，正如我们对人类免疫机制进行直接评估的能力一样。这是免疫耐受网络（ITN）方法的基石——对新型耐受性疗法进行临床评估，同时评估疾病的细胞、遗传和免疫机制，以及它们对治疗的反应如何改变。在这份更新申请中，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。我们将概述一个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、面向未来的组织，准备领导和采用目前未知的未来创新。我们建议建立一个包括数百名研究者、顾问和临床站点的合作结构

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.