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CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity
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CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity
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Journal Article
CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity
2019
Overview
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.
Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T cells) are a promising new treatment for cancer, but are associated with unique toxicities. Here, the authors test CAR-T-cell-derived exosomes as a surrogate for CAR-T cells and show that they can elicit a potent antitumour immune response in preclinical models of breast cancer with reduced signs of cytokine release syndrome compared with CAR-T therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/109
/ 13/31
/ 13/89
/ 14/19
/ 64/60
/ Animals
/ Antigens
/ Exosomes
/ Humanities and Social Sciences
/ Humans
/ Immunotherapy, Adoptive - methods
/ Lymphocyte Activation - immunology
/ Receptors, Antigen, T-Cell - immunology
/ Receptors, Antigen, T-Cell - metabolism
/ Receptors, Chimeric Antigen - immunology
/ Receptors, Chimeric Antigen - metabolism
/ Science
/ Therapy
/ Toxicity
/ Tumors
