National Institutes of Health, Clinical Center, Center for Cellular Engineering, Bethesda, USA.
Int Rev Immunol. 2022;41(6):638-648. doi: 10.1080/08830185.2022.2067154. Epub 2022 Apr 29.
Engineered T cell therapies such as CAR-T cells and TCR-T cells have generated impressive patient responses in previously incurable diseases. In the past few years there have been a number of technical innovations that enable robust clinical manufacturing in functionally closed and often automated systems. Here we describe the latest technology used to manufacture CAR- and TCR-engineered T cells in the clinic, including cell purification, transduction/transfection, expansion and harvest. To help compare the different systems available, we present three case studies of engineered T cells manufactured for phase I clinical trials at the NIH Clinical Center (CD30 CAR-T cells for lymphoma, CD19/CD22 bispecific CAR-T cells for B cell malignancies, and E7 TCR T cells for human papilloma virus-associated cancers). Continued improvement in cell manufacturing technology will help enable world-wide implementation of engineered T cell therapies.
工程化 T 细胞疗法，如 CAR-T 细胞和 TCR-T 细胞，在以前无法治愈的疾病中产生了令人印象深刻的患者应答。在过去的几年中，出现了许多技术创新，使功能封闭且通常自动化的系统能够进行强大的临床制造。在这里，我们描述了用于在临床上制造 CAR 和 TCR 工程化 T 细胞的最新技术，包括细胞纯化、转导/转染、扩增和收获。为了帮助比较可用的不同系统，我们展示了在 NIH 临床中心进行的 I 期临床试验中制造的三种工程化 T 细胞的案例研究（淋巴瘤用的 CD30 CAR-T 细胞、B 细胞恶性肿瘤用的 CD19/CD22 双特异性 CAR-T 细胞和人乳头瘤病毒相关癌症用的 E7 TCR T 细胞）。细胞制造技术的持续改进将有助于在全球范围内实施工程化 T 细胞疗法。
