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.
Rachel Grosser  1 ,  Leonid Cherkassky  2 ,  Navin Chintala  1 ,  Prasad S Adusumilli  3
Affiliations
  • 1. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 2. Surgical Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer, New York, NY 10065, USA.
  • 3. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: [email protected].
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.