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[嵌合抗原受体T细胞疗法治疗T细胞恶性肿瘤:挑战与最新进展]

[CAR T-cell therapy for T cell malignancies: challenges and recent advances].

作者信息

Tashiro Haruko

机构信息

Department of Hematology/Oncology, Teikyo University School of Medicine.

出版信息

Rinsho Ketsueki. 2024;65(7):644-651. doi: 10.11406/rinketsu.65.644.

Abstract

T cell malignancies pose several unique issues for CAR-T cell therapy that were not significant concerns with CAR-T cells for B-cell malignancies. A general problem to consider in the production of CAR-T cells is "on target-off tumor toxicity." This occurs when the antigen targeted by the CAR-T cells is also expressed on normal cells, not just tumor cells, which causes CAR-T cells to damage these normal cells. In CAR-T cell therapy for T cell tumors, antigens expressed on T cells (such as CD5, CD7, etc.) are the targets, which leads to a problem known as "fratricide," where CAR-T cells kill each other. Other issues include T cell aplasia and contamination of CAR-T cell products with tumor cells. However, several recent clinical trials have shown excellent outcomes for CAR-T cell therapy when genome editing technology is used to overcome these issues by knocking out target antigens or T cell receptors. This review article outlines these challenges and their solutions and discusses the results of recent clinical trials.

摘要

T细胞恶性肿瘤给CAR-T细胞疗法带来了几个独特的问题,而这些问题在用于B细胞恶性肿瘤的CAR-T细胞治疗中并非重大问题。在CAR-T细胞生产过程中需要考虑的一个普遍问题是“靶向非肿瘤毒性”。当CAR-T细胞靶向的抗原不仅在肿瘤细胞上表达,也在正常细胞上表达时,就会出现这种情况,这会导致CAR-T细胞损伤这些正常细胞。在针对T细胞肿瘤的CAR-T细胞疗法中,T细胞上表达的抗原(如CD5、CD7等)是靶点,这就导致了一个被称为“自相残杀”的问题,即CAR-T细胞相互杀伤。其他问题包括T细胞发育不全以及CAR-T细胞产品被肿瘤细胞污染。然而,最近的几项临床试验表明,当使用基因组编辑技术通过敲除靶抗原或T细胞受体来克服这些问题时,CAR-T细胞疗法能取得优异的疗效。这篇综述文章概述了这些挑战及其解决方案,并讨论了近期临床试验的结果。

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