The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth
The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth
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来自 CAR-T 细胞的外泌体有效靶向间皮素并减少三阴性乳腺癌的生长
DOI：
10.1016/j.cellimm.2020.104262
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发表时间：
2021-02-01
影响因子：
4.3
通讯作者：
Jie, Jing
中科院分区：
文献类型：
--
作者：
Yang, Pengxiang;Cao, Xingjian;Jie, Jing
表达嵌合抗原受体（CAR）的基因工程T细胞已迅速发展成为癌症患者的强大和创新的治疗模式。然而，剂量依赖性全身毒性的问题不容忽视。在这项研究中，分离了来自间皮素（MSLN）靶向CAR-T细胞的外泌体，我们发现它们保持了亲本T细胞的大多数特征，包括汽车和CD 3的表面表达。此外，携带CAR的外泌体显著抑制内源性和外源性MSLN阳性三阴性乳腺癌（TNBC）细胞的生长。效应分子穿孔素和颗粒酶B的表达可能是肿瘤杀伤的机制。更重要的是，在体内施用CAR-T细胞外泌体时观察到了高效的肿瘤抑制率，没有明显的副作用。因此，CAR-T细胞外泌体的使用具有针对表达MSLN的TNBC的巨大治疗潜力。
Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC.