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

Nature Communications - Tập 10 Số 1
Wenyan Fu1, Changhai Lei2, Shuowu Liu3, Yingshu Cui3, Chuqi Wang3, Kewen Qian3, Li Tian2, Yafeng Shen2, Xiaoyan Fan2, Fangxing Lin2, Min Ding4, Mingzhu Pan2, Xuting Ye2, Yongji Yang2, Shi Hu3
1Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, 200011, Shanghai, China
2Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China
3Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China
4Pharchoice Therapeutics Inc., 201406, Shanghai, China

Tóm tắt

AbstractGenetically 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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