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

加速细胞免疫疗法的开发，用于治疗危及生命的儿童疾病

• 批准号: 9750848
• 负责人: JULIE R PARK
• 金额: $ 141.62万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750848
• 关键词: Academia; Accelerated Phase; Adolescent; Adult; Affect; Allogenic; Autoimmune Diseases; Autoimmunity; Award; Biological; Biological Assay; CAR T cell therapy; Caring; Cell Therapy; Cells; Cellular immunotherapy; Child; Childhood; Clinical Research; Clinical Trials; Clinical and Translational Science Awards; Collaborations; Disease; Eligibility Determination; Engineering; Ensure; Future; Generations; Goals; Graft Rejection; Grant; Immune; Immune Tolerance; Immune system; Immunity; Immunotherapeutic agent; Industry; Infection; Infrastructure; Institution; Investigational Drugs; Investigational New Drug Application; Investments; Lead; Life; Longevity; Lymphoproliferative Disorders; Malignant Neoplasms; Medicine; Minority; Modality; Monitor; Multi-Institutional Clinical Trial; Natural Killer Cells; Organ Transplantation; Outcome; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Phase I Clinical Trials; Pilot Projects; Population; Positioning Attribute; Procedures; Process; Production; Rare Diseases; Refractory; Regulatory Affairs; Regulatory T-Lymphocyte; Research Personnel; Role; Safety; Site; Solid; T cell therapy; Therapeutic; Time; Training; Translational Research; Translations; Underserved Population; Viral; Virus Diseases; Work; base; cellular development; cellular engineering; clinical development; clinical efficacy; clinical research site; design; graft vs host disease; hematopoietic cell transplantation; high risk; human disease; immunotherapy clinical trials; immunotherapy trials; innovation; innovative technologies; investigator training; leukemia; novel; phase 2 study; programs; research and development; response; success; therapy development

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.

项目总结及摘要 免疫失调或功能失调在人类疾病状态中已有充分记录，从自身免疫 对感染和癌症的免疫力。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正潜力。但复杂性和费用 与患者和疾病特异性的细胞疗法的产生相关，禁止广泛 当前时间的应用程序。罕见儿科疾病的治疗进展进一步受到阻碍 事实上，在许多情况下，投资的财务回报并不被认为有利于行业赞助 研究与开发。此 U01 创新奖申请旨在加速 通过建立细胞免疫疗法来治疗影响儿童和青少年的疾病 由四级护理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转化科学奖 (CTSA) 项目。我们的目标是加速 实施癌症工程细胞治疗产品（包括嵌合抗原受体-T 细胞疗法和 NK 细胞疗法）或用于治疗淋巴增殖性疾病的选择免疫细胞疗法 疾病和病毒性疾病（病毒特异性 T 细胞疗法）。此外，我们还将加速小说的创作 实施工程化调节性 T 细胞以激发免疫耐受作为治疗方式 多种疾病，包括同种异体造血细胞后的移植物抗宿主病 移植、实体器官移植后排斥反应和小儿自身免疫性疾病。我们提出一个 多管齐下，引领细胞免疫治疗临床试验的发展 儿科医学。我们的目标是扩大 cGMP 制造计划，并具备供应产品的能力 通过多中心临床试验，建立集中的临床试验/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 分析测定的可靠性和可靠性，以监测细胞免疫治疗试验的安全性和临床疗效，并 开展必要的合作，以在 U01 赠款的使用寿命结束后维持该基础设施 机制。每个参与的 CTSA 将重点培训翻译人员 中心并建立可以轻松传播到其他中心的标准流程和程序 未来。此外，我们将在学术界和制药业之间建立重要的合作关系，以确保长期 术语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展这些流程以实现 将细胞免疫治疗试验导出到所有 CTSA 站点并最终扩展到其他站点。