Accelerate cellular immunotherapy development for treatment of life-threatening childhood disorders

项目概要和摘要 免疫失调或功能失调在人类疾病状态中有充分的记载， 对感染和癌症免疫。更深入地了解免疫系统在人类疾病中的作用 带来了免疫导向细胞疗法的真实的潜力。然而，复杂性和费用 与患者和疾病特异性的细胞疗法的产生相关， 目前的应用。罕见儿科疾病的进展进一步受到 事实上，在许多情况下，投资的财务回报并不被认为是有利于行业赞助的 研发的U 01创新奖申请旨在加速以下内容的翻译 细胞免疫疗法，以治疗影响儿童和青少年的疾病， 儿科细胞免疫治疗联盟由四级护理儿科医院组成 临床和转化科学奖（CTSA）。我们的目标是加快 用于癌症的工程化细胞治疗产品（包括嵌合抗原受体-T 细胞疗法和NK细胞疗法）或选择的免疫细胞疗法 疾病和病毒性疾病（病毒特异性T细胞疗法）。此外，我们还将加快小说 实施工程化的调节性T细胞以引起免疫耐受作为治疗模式， 包括同种异体造血细胞移植后移植物抗宿主病在内的多种疾病 移植、实体器官移植后排斥反应和儿科自身免疫性疾病。我们提出了一个 多管齐下的方法，率先发展细胞免疫治疗的临床试验， 儿科医学我们的目标是扩大cGMP生产计划，以提供产品 通过多中心临床试验，建立集中的临床试验/法规事务协调办公室， 高效开展儿科罕见病细胞免疫治疗临床研究，提高效率 分析测定的可靠性，以监测细胞免疫治疗试验的安全性和临床疗效， 发展必要的合作，以在U 01赠款的有效期之后维持这一基础设施 机制将有一个直接的重点培训翻译劳动力在每个参与CTSA 建立标准流程和程序，便于向联合国其他中心传播。 未来此外，我们将在学术界和制药业之间建立关键的合作，以确保长期的 长期可持续性，并扩大我们对适用的成人疾病状态的进展。虽然我们最初的工作 我们将开发有限的CTSA站点联盟，我们的长期目标是扩展这些流程，以实现 将细胞免疫治疗试验输出到所有CTSA研究中心，并最终输出到其他研究中心。

Project Summary & Abstract Dysregulated or dysfunctional immunity is well documented in human disease states ranging from auto- immunity to infection and cancer. A deeper understanding of the role of the immune system in human disease brings with it the real potential of immune-directed cellular therapies. However, the complexity and expense associated with the generation of cell therapies that are both patient- and disease-specific prohibit broad application at the current time. Progress in the setting of rare pediatric conditions is further hampered by the fact that the financial returns on investment are in many cases not considered favorable for industry-sponsored research and development. This U01 Innovative Award application is designed to accelerate the translation of cellular immunotherapies to treat disorders that affect children and adolescents through the establishment of the Consortium for Pediatric Cellular Immunotherapy comprised of quaternary care pediatric hospitals affiliated with their Clinical and Translational Science Award (CTSA) programs. We aim to accelerate the implementation of engineered cellular therapeutic products for cancer (including chimeric-antigen receptor-T cell therapy and NK cell therapy) or selected immune cellular therapies for treatment of lymphoproliferative disorders, and viral diseases (viral-specific T cell therapy). In addition, we will also accelerate the novel implementation of engineered regulatory T-cells to invoke immune tolerance as a therapeutic modality for a wide range of disorders that include graft vs. host disease following allogeneic hematopoietic cell transplantation, rejection after solid organ transplantation and pediatric auto-immune diseases. We propose a multi-pronged approach to spearhead the development of cellular immunotherapy clinical trials in pediatric medicine. We aim to expand cGMP manufacturing programs with the capacity to supply products through multi-center clinical trials, to establish a centralized clinical trials/regulatory affairs coordinating office to efficiently implement cellular immunotherapy clinical research for rare pediatric diseases, to increase efficiency and reliability of analytic assays to monitor safety and clinical efficacy of cellular immunotherapy trials and to develop collaborations necessary to sustain this infrastructure beyond the life span of the U01 grant mechanism. There will be a directed focus on training the translational workforce at each participating CTSA hub and establishing standard processes and procedures that can be easily disseminated to other hubs in the future. Moreover, within we will establish key collaborations between academia and pharma to ensure long term sustainability and to broaden our advances towards applicable adult disease states. While our initial work will develop a limited consortium of CTSA sites, our long-term goal is to expand these processes to enable export of cellular immunotherapy trials to all CTSA sites and ultimately beyond.