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

Wenyan Fu, Changhai Lei, Shuowu Liu, Yingshu Cui, Chuqi Wang, Kewen Qian, Tian Li, Yafeng Shen, Xiaoyan Fan, Fangxing Lin, Min Ding, Mingzhu Pan, Xuting Ye, Yongji Yang and Shi Hu ()
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Wenyan Fu: Shanghai Jiao Tong University School of Medicine Shanghai
Changhai Lei: Second Military Medical University
Shuowu Liu: Second Military Medical University
Yingshu Cui: Second Military Medical University
Chuqi Wang: Second Military Medical University
Kewen Qian: Second Military Medical University
Tian Li: Second Military Medical University
Yafeng Shen: Second Military Medical University
Xiaoyan Fan: Second Military Medical University
Fangxing Lin: Second Military Medical University
Min Ding: Pharchoice Therapeutics Inc.
Mingzhu Pan: Second Military Medical University
Xuting Ye: Second Military Medical University
Yongji Yang: Second Military Medical University
Shi Hu: Second Military Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12321-3

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