Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors

Cancer Cell. 2019 Nov 11;36(5):471-482. doi: 10.1016/j.ccell.2019.09.006.

Abstract

Checkpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response. This can be further amplified by the addition of CPB agents, which serve to counteract the immune inhibitory environment undermining optimal CAR T cell efficacy. Herein, we review preclinical and clinical combination therapy with CAR T cells and CPB agents, with a focus on solid tumor malignancies.

Keywords: CAR T cell; PD-1; checkpoint blockade; chimeric antigen receptor; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Combined Modality Therapy / methods
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors*
  • Costimulatory and Inhibitory T-Cell Receptors / immunology
  • Costimulatory and Inhibitory T-Cell Receptors / metabolism
  • Disease Models, Animal
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Randomized Controlled Trials as Topic
  • Receptors, Chimeric Antigen / immunology*
  • Treatment Outcome
  • Tumor Escape / drug effects
  • Tumor Escape / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Costimulatory and Inhibitory T-Cell Receptors
  • Receptors, Chimeric Antigen