{"title":"制造嵌合抗原受体免疫细胞疗法的进展。","authors":"Apoorva Ramamurthy, Anna Tommasi, Krishanu Saha","doi":"10.1007/s00281-024-01019-4","DOIUrl":null,"url":null,"abstract":"<p><p>Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"46 5","pages":"12"},"PeriodicalIF":7.9000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Advances in manufacturing chimeric antigen receptor immune cell therapies.\",\"authors\":\"Apoorva Ramamurthy, Anna Tommasi, Krishanu Saha\",\"doi\":\"10.1007/s00281-024-01019-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering.</p>\",\"PeriodicalId\":21704,\"journal\":{\"name\":\"Seminars in Immunopathology\",\"volume\":\"46 5\",\"pages\":\"12\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2024-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Seminars in Immunopathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00281-024-01019-4\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Seminars in Immunopathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00281-024-01019-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
生物医学研究在制造嵌合抗原受体 T 细胞(CAR-T)疗法方面取得了长足进步,标志着细胞免疫疗法进入了变革时代。然而,现有的自体细胞疗法制造方法在成本、免疫细胞来源、安全风险和可扩展性等方面仍存在一些挑战。这些挑战促使人们最近努力利用自动化封闭系统生物反应器和人工智能模型来优化细胞疗法的工艺开发和生产。与此同时,mRNA、CRISPR 基因组编辑和转座子等非病毒基因转移方法也被应用于 T 细胞和其他免疫细胞(如巨噬细胞和自然杀伤细胞)的工程化。目前正在开发原始免疫细胞和干细胞的替代来源,以产生通用的异体疗法,这标志着目前的自体疗法模式正在发生转变。这些多方面的生产创新凸显了在不断变化的癌症治疗环境中,推动这种治疗方法走向更广泛临床应用和改善患者预后的集体努力。在此,我们回顾了当前的 CAR 免疫细胞制造策略,并重点介绍了细胞疗法规模化、自动化、工艺开发和工程学方面的最新进展。
Advances in manufacturing chimeric antigen receptor immune cell therapies.
Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering.
期刊介绍:
The aim of Seminars in Immunopathology is to bring clinicians and pathologists up-to-date on developments in the field of immunopathology.For this purpose topical issues will be organized usually with the help of a guest editor.Recent developments are summarized in review articles by authors who have personally contributed to the specific topic.