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

点击翻译按钮获取中文摘要

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.