CAR-modified T-cell therapy for cancer: an updated review

Artif Cells Nanomed Biotechnol. 2016 Sep;44(6):1339-49. doi: 10.3109/21691401.2015.1052465. Epub 2015 Jun 11.

Abstract

The use of chimeric antigen receptor (CAR)-modified T cells is a promising approach for cancer immunotherapy. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in T-cell activation subsequent to antigen binding. Optimal tumor removal through CAR-modified T cells requires suitable target antigen selection, co-stimulatory signaling domain, and the ability of CAR T cells to traffic, persist, and retain antitumor function after adoptive transfer. There are several elements which can improve antitumor function of CAR T cells, including signaling, conditioning chemotherapy and irradiation, tumor burden of the disease, T-cell phenotype, and supplementary cytokine usage. This review outlines four generations of CAR. The pre-clinical and clinical studies showed that this technique has a great potential for treatment of solid and hematological malignancies. The main purpose of the current review is to focus on the pre-clinical and clinical developments of CAR-based immunotherapy.

Keywords: T cells; cancer; chimeric antigen receptor; clinical studies; immunotherapy.

Publication types

  • Review

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • Antigens, Neoplasm / immunology*
  • Humans
  • Lymphocyte Activation*
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • Recombinant Fusion Proteins* / genetics
  • Recombinant Fusion Proteins* / immunology

Substances

  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins