Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps

Pharmacol Ther. 2016 Oct:166:30-9. doi: 10.1016/j.pharmthera.2016.06.010. Epub 2016 Jun 29.

Abstract

Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers to CAR T cell efficacy and mechanisms underlying these barriers, outline potential avenues for overcoming these therapeutic obstacles, and discuss the future of translating CAR T cells for the treatment of patients with solid malignancies.

Keywords: CAR T cells; Cellular immunity; Chimeric antigen receptor; Solid malignancies; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • GPI-Linked Proteins / immunology
  • Genes, Transgenic, Suicide / physiology
  • Genes, erbB-1 / immunology
  • Humans
  • Immune Tolerance / immunology
  • Immunity, Cellular / immunology
  • Immunotherapy, Adoptive / methods*
  • Mesothelin
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Tumor Microenvironment

Substances

  • GPI-Linked Proteins
  • Receptors, Antigen, T-Cell
  • Mesothelin