Roger Williams Medical Center, Immuno-oncology Institute, Providence, RI, United States; Boston University Medical Center, Department of Surgery, Boston, MA, United States.
Roger Williams Medical Center, Immuno-oncology Institute, Providence, RI, United States; Boston University Medical Center, Department of Surgery, Boston, MA, United States; TriSalus™ Life Sciences, Inc., Westminster, CO, United States; Roger Williams Medical Center, Department of Medicine, Providence, RI, United States.
Methods Cell Biol. 2022;167:203-226. doi: 10.1016/bs.mcb.2021.11.003. Epub 2021 Dec 13.
Chimeric Antigen Receptor T cell (CAR-T) therapies have demonstrated promising clinical response rates for patients with hematological malignancies. CAR-T cells are generated by bioengineering patient T cells to express CAR proteins that can specifically target tumor antigens. For CAR-T therapy to be effective in solid tumors, several factors including trafficking, activation, expansion, and persistence are important considerations in hostile tumor microenvironment (TME). Despite significant advances in CAR-T therapies, clinical success in solid tumor indications has been limited. The complex processes involved in CAR-T manufacturing and quality control (QC) contribute to high cost of these therapies, creating barriers to widespread adoption. The processes involved are not uniformly standardized and may require numerous manual handling steps. This chapter details strategies to overcome barriers to broad CAR-T application and reviews current production processes used for CAR-T manufacturing. Emphasis is placed on reproducibility, manufacturing costs, and product release testing. Implementing new processing alternatives and innovative CAR-T designs, along with further innovation and efficiencies will be key to more consistent CAR-T cell therapy success.
嵌合抗原受体 T 细胞（CAR-T）疗法已证明对血液系统恶性肿瘤患者具有有前景的临床反应率。CAR-T 细胞通过生物工程改造患者 T 细胞来表达 CAR 蛋白，这些蛋白可以特异性地靶向肿瘤抗原。为了使 CAR-T 疗法在实体瘤中有效，包括运输、激活、扩增和持久性在内的几个因素是在恶劣的肿瘤微环境（TME）中需要重要考虑的因素。尽管 CAR-T 疗法取得了重大进展，但在实体瘤适应证中的临床成功有限。CAR-T 制造和质量控制（QC）所涉及的复杂过程导致这些疗法的成本高昂，这成为广泛采用的障碍。所涉及的过程没有统一标准化，可能需要许多手动处理步骤。本章详细介绍了克服广泛应用 CAR-T 的障碍的策略，并回顾了用于 CAR-T 制造的当前生产工艺。重点放在可重复性、制造成本和产品放行测试上。实施新的处理替代方案和创新的 CAR-T 设计，以及进一步的创新和效率将是实现更一致的 CAR-T 细胞治疗成功的关键。
