文章目录

克服细胞外囊泡介导的自相残杀改善了CAR - T细胞对实体肿瘤的治疗

原文发布日期：2025-04-15

英文摘要：

摘要翻译：

原文链接：

文章：

克服细胞外囊泡介导的自相残杀改善了CAR - T细胞对实体肿瘤的治疗

Overcoming extracellular vesicle-mediated fratricide improves CAR T cell treatment against solid tumors

原文发布日期：2025-04-15

英文摘要：

The efficacy of chimeric antigen receptor (CAR) T cells against solid tumors is limited. The molecular mechanisms underlying CAR T cell resistance are yet to be elucidated and new strategies need to be developed to improve treatment outcomes. Here we report that solid tumors respond to CAR T cells by upregulating the secretion of small extracellular vesicles carrying tumor antigens, which are horizontally transferred to CAR T cells, leading to antigen recognition and CAR T cell fratricide. Engineered CAR T cells armored with Serpin B9, a major granzyme B inhibitor, show decreased fratricide and increased vitality, tumor infiltration, and antitumor activity in female mice. Moreover, Serpin B9-armored CAR T cells show higher efficacy than parental CAR T cells in treating solid tumors when combined with the anti-programmed death 1 antibody. Our study demonstrates a mechanism that limits CAR T cell function and suggests an improved strategy in tumor treatment.

摘要翻译：

与实体瘤的相互作用有限。与实体瘤抗性的分子机制尚待阐明，开发新策略以提高治疗效果尚有需求。我们发现，实体瘤通过上调分泌携带肿瘤抗原的小细胞外泡，这些小泡水平上转移到 CAR T 细胞，导致抗原识别并引发 CAR T 细胞间的共融。武装有 Serrin B9 的工程化 CAR T 细胞在小鼠中显示降低了共融，提高了活力、肿瘤侵袭性和抗肿瘤活性。此外，Serrin B9-武装的 CAR T 细胞在结合 anti-PD-1 抗体时，在治疗实体瘤方面具有更高的疗效。