Impact of Manufacturing Procedures on CAR T Cell Functionality.
Impact of Manufacturing Procedures on CAR T Cell Functionality.
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DOI：
10.3389/fimmu.2022.876339
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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嵌合抗原受体（CAR）修饰的T细胞疗法的领域在过去几十年中迅速扩大。截至目前，已有六种CAR T细胞产品获得FDA批准：Kymriah（tisagenlecleucel，CD 19 CAR T细胞），YECARTA（axicabtagene ciloleucel，CD 19 CAR T细胞），TECARTUS（brexucabtagene autoleucel，CD 19 CAR T细胞），BREYANZI（lisocabtagene maraleucel，CD 19 CAR T细胞），ABECMA（idecabtagene vicleucel，BCMA CAR T细胞）和CARVYKTI（ciltacabtagene autoleucel，BCMA CAR T细胞）。随着这种临床成功，CAR T细胞疗法已成为对抗癌症的最有前途的治疗选择之一。目前的研究工作集中在进一步增强其在无应答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，离体培养条件可能会显著影响CAR T细胞的功能-这是临床翻译过程中经常被忽视的方面。在这篇综述中，我们专注于CAR T细胞的体外制造过程，并讨论它如何影响CAR T细胞功能。
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, ex vivo culture conditions could significantly impact CAR T cell functionality – an often overlooked aspect during clinical translation. In this review, we focus on the ex vivo manufacturing process for CAR T cells and discuss how it impacts CAR T cell function.