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

Author

Listed:
  • Wenyan Fu

    (Shanghai Jiao Tong University School of Medicine Shanghai)

  • Changhai Lei

    (Second Military Medical University
    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
    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
    Second Military Medical University)

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.

Suggested Citation

  • 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 & Shi Hu, 2019. "CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12321-3
    DOI: 10.1038/s41467-019-12321-3
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    Cited by:

    1. Wenyi Zheng & Julia Rädler & Helena Sork & Zheyu Niu & Samantha Roudi & Jeremy P. Bost & André Görgens & Ying Zhao & Doste R. Mamand & Xiuming Liang & Oscar P. B. Wiklander & Taavi Lehto & Dhanu Gupta, 2023. "Identification of scaffold proteins for improved endogenous engineering of extracellular vesicles," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Hsin-Fang Chang & Claudia Schirra & Momchil Ninov & Ulrike Hahn & Keerthana Ravichandran & Elmar Krause & Ute Becherer & Štefan Bálint & Maria Harkiolaki & Henning Urlaub & Salvatore Valitutti & Cosim, 2022. "Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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