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

项目摘要(&A) 免疫功能失调或功能失调在人类疾病状态下被很好地记录下来，从自体- 对感染和癌症具有免疫力。更深入地了解免疫系统在人类疾病中的作用 它带来了免疫导向细胞疗法的真正潜力。然而，复杂性和成本 与针对患者和疾病的细胞疗法的产生有关 应用程序在当前时间。在罕见儿科疾病的设定方面的进展进一步受阻于 在许多情况下，投资的财务回报被认为不利于行业赞助的事实 研究和开发。这个U01创新奖项应用程序旨在加速翻译 通过建立细胞免疫疗法来治疗影响儿童和青少年的疾病 由四级儿科医院组成的儿科细胞免疫治疗联盟 隶属于他们的临床和翻译科学奖(CTSA)计划。我们的目标是加快 癌症工程化细胞治疗产品(包括嵌合抗原受体-T)的实施 细胞疗法和NK细胞疗法)或用于治疗淋巴增生性疾病的选定免疫细胞疗法 疾病和病毒疾病(病毒特异性T细胞疗法)。此外，我们还将加快小说的速度 工程调节性T细胞的实施，以调用免疫耐受作为一种治疗方式 广泛的疾病，包括异基因造血细胞引起的移植物对宿主疾病 移植、实体器官移植后的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，带头开展细胞免疫治疗临床试验 儿科医学。我们的目标是扩大cGMP制造计划，使其具有供应产品的能力 通过多中心临床试验，建立集中的临床试验/监管事务协调办公室，以 高效开展儿科罕见病细胞免疫治疗临床研究，提高工作效率 用于监测细胞免疫治疗试验的安全性和临床有效性的分析分析的可靠性以及 开展必要的协作，使此基础设施在U01资助金的有效期内得以维持 机制。每个参与的CTSA将有针对性地专注于培训翻译工作人员 并建立标准流程和程序，这些流程和程序可以很容易地传播到 未来。此外，我们将在学术界和制药公司之间建立重要的合作关系，以确保长期 长期可持续性，并扩大我们在适用的成人疾病状态方面的进展。虽然我们最初的工作 将开发一个有限的CTSA站点联盟，我们的长期目标是扩大这些流程，以实现 将细胞免疫治疗试验输出到所有CTSA站点，并最终扩展到其他站点。

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.