Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors

Sci China Life Sci. 2016 Apr;59(4):340-8. doi: 10.1007/s11427-016-5027-4. Epub 2016 Mar 11.

Abstract

Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

Keywords: T cells; chimeric antigen receptor; solid tumors.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

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