CAR-Ts: new perspectives in cancer therapy

FEBS Lett. 2022 Feb;596(4):403-416. doi: 10.1002/1873-3468.14270. Epub 2022 Jan 12.

Abstract

Chimeric antigen receptor (CAR)-T-cell therapy is a promising anticancer treatment that exploits the host's immune system to fight cancer. CAR-T cell therapy relies on immune cells being modified to express an artificial receptor targeting cancer-specific markers, and infused into the patients where they will recognize and eliminate the tumour. Although CAR-T cell therapy has produced encouraging outcomes in patients with haematologic malignancies, solid tumours remain challenging to treat, mainly due to the lack of cancer-specific molecular targets and the hostile, often immunosuppressive, tumour microenvironment. CAR-T cell therapy also depends on the quality of the injected product, which is closely connected to CAR design. Here, we explain the technology of CAR-Ts, focusing on the composition of CARs, their application, and limitations in cancer therapy, as well as on the current strategies to overcome the challenges encountered. We also address potential future targets to overcome the flaws of CAR-T cell technology in the treatment of cancer, emphasizing glycan antigens, the aberrant forms of which attain high tumour-specific expression, as promising targets for CAR-T cell therapy.

Keywords: CAR-T; cancer; cell therapy; chimeric antigen receptor; glycans; glycosylation; tumour therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Binding Sites
  • Carbohydrate Sequence
  • Genetic Engineering / methods
  • Glycosylation
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • Protein Binding
  • Protein Domains
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Antigens, Neoplasm
  • Polysaccharides
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen