The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth

被引:102
|
作者
Yang, Pengxiang [1 ,2 ,3 ]
Cao, Xingjian [4 ]
Cai, Huilong [3 ]
Feng, Panfeng [5 ]
Chen, Xiang [4 ]
Zhu, Yihua [4 ]
Yang, Yue [3 ]
An, Weiwei [3 ]
Yang, Yumin [1 ,2 ]
Jie, Jing [4 ]
机构
[1] Nantong Univ, Key Lab Neuroregenerat Jiangsu, Nantong 226001, Peoples R China
[2] Nantong Univ, Minist Educ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China
[3] Harbin Med Univ, Heilongjiang Acad Med Sci, Inst Canc Prevent & Treatment, Harbin 150081, Peoples R China
[4] Nantong Univ, Peoples Hosp Nantong 1, Affiliated Hosp 2, Dept Clin Lab, Nantong, Peoples R China
[5] Nantong Univ, Peoples Hosp Nantong 1, Affiliated Hosp 2, Dept Pharm, Nantong 226001, Peoples R China
基金
中国国家自然科学基金;
关键词
CAR-T; Exosomes; Mesothelin; Triple-negative breast cancer; Tumor immunotherapy; IMMUNOTHERAPY; METASTASIS; DELIVERY;
D O I
10.1016/j.cellimm.2020.104262
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:11
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