Статья

CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity

Wenyan FuDepartment of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, 200011, Shanghai, ChinaChanghai LeiDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaShuowu LiuTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, ChinaYingshu CuiTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, ChinaChuqi WangTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, ChinaKewen QianTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, ChinaLi TianDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaYafeng ShenDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaXiaoyan FanDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaFangxing LinDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaMin DingMingzhu PanDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaXuting YeDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaYongji YangDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, ChinaShi HuDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. [email protected]

2019en

ABI

Аннотация

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. Here, we report that CAR-T cells release extracellular vesicles, mostly in the form of exosomes that carry CAR on their surface. The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. Compared with CAR-T cells, CAR exosomes do not express Programmed cell Death protein 1 (PD1), and their antitumour effect cannot be weakened by recombinant PD-L1 treatment. In a preclinical in vivo model of cytokine release syndrome, the administration of CAR exosomes is relatively safe compared with CAR-T therapy. This study supports the use of exosomes as biomimetic nanovesicles that may be useful in future therapeutic approaches against tumours.

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Идентификаторы

DOI: 10.1038/s41467-019-12321-3

Цитирования и источники

Цитирований: 4Использованных источников: 0

Показатели — AkademScholar