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

Nat Commun. 2019 Sep 25;10(1):4355. doi: 10.1038/s41467-019-12321-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Cell Line, Tumor
  • Exosomes / immunology*
  • Exosomes / metabolism
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation / immunology
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / metabolism
  • Xenograft Model Antitumor Assays / methods*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen