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制造工艺对 CAR T 细胞功能的影响。

Impact of Manufacturing Procedures on CAR T Cell Functionality.

机构信息

Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, United States.

Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States.

出版信息

Front Immunol. 2022 Apr 13;13:876339. doi: 10.3389/fimmu.2022.876339. eCollection 2022.

DOI:10.3389/fimmu.2022.876339
PMID:35493513
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9043864/
Abstract

The field of chimeric antigen receptor (CAR) modified T cell therapy has rapidly expanded in the past few decades. As of today, there are six CAR T cell products that have been approved by the FDA: KYMRIAH (tisagenlecleucel, CD19 CAR T cells), YESCARTA (axicabtagene ciloleucel, CD19 CAR T cells), TECARTUS (brexucabtagene autoleucel, CD19 CAR T cells), BREYANZI (lisocabtagene maraleucel, CD19 CAR T cells), ABECMA (idecabtagene vicleucel, BCMA CAR T cells) and CARVYKTI (ciltacabtagene autoleucel, BCMA CAR T cells). With this clinical success, CAR T cell therapy has become one of the most promising treatment options to combat cancers. Current research efforts focus on further potentiating its efficacy in non-responding patients and solid tumor settings. To achieve this, recent evidence suggested that, apart from developing next-generation CAR T cells with additional genetic modifications, culture conditions could significantly impact CAR T cell functionality - an often overlooked aspect during clinical translation. In this review, we focus on the manufacturing process for CAR T cells and discuss how it impacts CAR T cell function.

摘要

嵌合抗原受体 (CAR) 修饰 T 细胞疗法在过去几十年中迅速发展。截至今日,已有六种 CAR T 细胞产品获得 FDA 批准:KYMRIAH(tisagenlecleucel,CD19 CAR T 细胞)、YESCARTA(axicabtagene ciloleucel,CD19 CAR T 细胞)、TECARTUS(brexucabtagene autoleucel,CD19 CAR T 细胞)、BREYANZI(lisocabtagene maraleucel,CD19 CAR T 细胞)、ABECMA(idecabtagene vicleucel,BCMA CAR T 细胞)和 CARVYKTI(ciltacabtagene autoleucel,BCMA CAR T 细胞)。随着这一临床成功,CAR T 细胞疗法已成为对抗癌症最有前途的治疗选择之一。目前的研究重点是进一步提高其在无反应患者和实体瘤环境中的疗效。为了实现这一目标,最近的证据表明,除了开发具有额外遗传修饰的下一代 CAR T 细胞外,培养条件也可能显著影响 CAR T 细胞的功能——这是临床转化过程中经常被忽视的一个方面。在这篇综述中,我们重点介绍了 CAR T 细胞的制造工艺,并讨论了其如何影响 CAR T 细胞的功能。

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