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The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth
Cellular Immunology ( IF 4.3 ) Pub Date : 2020-12-18 , DOI: 10.1016/j.cellimm.2020.104262
Pengxiang Yang 1 , Xingjian Cao 2 , Huilong Cai 3 , Panfeng Feng 4 , Xiang Chen 2 , Yihua Zhu 2 , Yue Yang 3 , Weiwei An 3 , Yumin Yang 5 , Jing Jie 2
Affiliation  

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.



中文翻译:

源自CAR-T细胞的外泌体有效地靶向间皮素并减少三阴性乳腺癌的生长

表达嵌合抗原受体(CAR)的基因工程T细胞已迅速发展为癌症患者的强大而创新的治疗方式。但是,剂量依赖性全身毒性的问题不容忽视。在这项研究中,分离了靶向间皮素(MSLN)的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CAR和CD3的表面表达。此外,携带CAR的外泌体显着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的表达可能是杀死肿瘤的一种机制。更重要的是,在体内施用CAR-T细胞外泌体时观察到高效的肿瘤抑制率,而没有明显的副作用。因此,CAR-T细胞外泌体的使用对表达MSLN的TNBC具有巨大的治疗潜力。

更新日期:2020-12-26
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