肿瘤细胞治疗研究
英文原题：CD5 deletion enhances the antitumor activity of adoptive T cell therapies.
这些发现表明，CD5 是 T 细胞功能的关键抑制因子，也是增强 T 细胞疗法的潜在临床靶点。
多数接受FDA批准CAR-T治疗的患者最终会进展；实体瘤及预后极差的T细胞淋巴瘤等血液肿瘤中，CAR-T也未实现治愈。过继T细胞疗法临床成功的主要障碍之一是CAR-T功能障碍，以及输注后扩增或持久性不足。本研究发现CD5可抑制CAR-T活化；用CRISPR-Cas9敲除CD5可在多种血液和实体瘤临床前模型中增强抗肿瘤作用。机制上，CD5敲除提升效应功能、细胞毒性、体内扩增及持久性，且未见明显毒性。结果表明CD5是T细胞功能的重要抑制因子，可能成为增强T细胞疗法的临床靶点。
Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.
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