Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors

Drugs. 2019 Mar;79(4):401-415. doi: 10.1007/s40265-019-01071-7.

Abstract

While impressive clinical responses have been observed using chimeric antigen receptor (CAR) T cells targeting CD19+ hematologic malignancies, limited clinical benefit has been observed using CAR T cells for a variety of solid tumors. Results of clinical studies have highlighted several obstacles which CAR T cells face in the context of solid tumors, including insufficient homing to tumor sites, lack of expansion and persistence, encountering a highly immunosuppressive tumor microenvironment, and heterogeneous antigen expression. In this review, we review clinical outcomes and discuss strategies to improve the antitumor activity of CAR T cells for solid tumors.

Publication types

  • Review

MeSH terms

  • Antigens, CD19
  • Antineoplastic Agents / therapeutic use*
  • Genes, Transgenic, Suicide
  • Genetic Therapy
  • Hematologic Neoplasms / drug therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / drug therapy*
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • Antigens, CD19
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Receptors, Chimeric Antigen