[CAR T 细胞疗法治疗 T 细胞恶性肿瘤:挑战与最新进展]。

Haruko Tashiro
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引用次数: 0

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,而这些问题在治疗 B 细胞恶性肿瘤的 CAR-T 细胞疗法中并不突出。生产 CAR-T 细胞需要考虑的一个普遍问题是 "靶向-肿瘤毒性"。当 CAR-T 细胞靶向的抗原也在正常细胞(而不仅仅是肿瘤细胞)上表达时,就会出现这种情况,从而导致 CAR-T 细胞损伤这些正常细胞。在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细胞会互相残杀。其他问题包括 T 细胞增生和 CAR-T 细胞产品被肿瘤细胞污染。不过,最近的几项临床试验显示,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细胞疗法取得了很好的疗效。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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[CAR T-cell therapy for T cell malignancies: challenges and recent advances].

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.

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