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


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.

SUBMITTER: Fu W 

PROVIDER: S-EPMC6761190 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Fu Wenyan W   Lei Changhai C   Liu Shuowu S   Cui Yingshu Y   Wang Chuqi C   Qian Kewen K   Li Tian T   Shen Yafeng Y   Fan Xiaoyan X   Lin Fangxing F   Ding Min M   Pan Mingzhu M   Ye Xuting X   Yang Yongji Y   Hu Shi S  

Nature communications 20190925 1


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-cont  ...[more]

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