肿瘤细胞治疗研究
英文原题：Scaling up and scaling out: Advances and challenges in manufacturing engineered T cell therapies.
工程化T细胞疗法，如CAR-T细胞和TCR-T细胞，在以往无法治愈的疾病中产生了令人瞩目的患者反应。
工程化T细胞疗法，如CAR-T细胞和TCR-T细胞，在以往无法治愈的疾病中产生了令人瞩目的患者缓解。在过去几年中，出现了许多技术创新，使得在功能封闭且通常自动化的系统中实现稳健的临床生产成为可能。在此，我们描述了用于临床生产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临床中心为I期临床试验生产的工程化T细胞的三个案例研究（用于淋巴瘤的CD30 CAR-T细胞、用于B细胞恶性肿瘤的CD19/CD22双特异性CAR-T细胞，以及用于人乳头瘤病毒相关癌症的E7 TCR T细胞）。细胞生产技术的持续改进将有助于实现工程化T细胞疗法的全球应用。
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.
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