Incorporation of immune checkpoint blockade into chimeric antigen receptor T cells (CAR-Ts): Combination or built-in CAR-T

Dok Hyun Yoon, Mark J. Osborn, Jakub Tolar, Chong Jai Kim

Research output: Contribution to journalReview articlepeer-review

67 Scopus citations

Abstract

Chimeric antigen receptor (CAR) T cell therapy represents the first U.S. Food and Drug Administration approved gene therapy and these engineered cells function with unprecedented efficacy in the treatment of refractory CD19 positive hematologic malignancies. CAR translation to solid tumors is also being actively investigated; however, efficacy to date has been variable due to tumor-evolved mechanisms that inhibit local immune cell activity. To bolster the potency of CAR-T cells, modulation of the immunosuppressive tumor microenvironment with immune-checkpoint blockade is a promising strategy. The impact of this approach on hematological malignancies is in its infancy, and in this review we discuss CAR-T cells and their synergy with immune-checkpoint blockade.

Original languageEnglish (US)
Article number340
JournalInternational journal of molecular sciences
Volume19
Issue number2
DOIs
StatePublished - Feb 2018

Bibliographical note

Funding Information:
Acknowledgments: This work was supported in part by Asan-Minnesota Institute for Innovating Transplantation (AMIT), Global Research Development Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) (NRF-2015K1A4A3046807) and the Corrigan family, and Children’s Cancer Research Fund.

Keywords

  • Adoptive T cell therapy
  • CRISPR/Cas9
  • Cancer immunotherapy
  • Chimeric antigen receptors
  • Gene editing
  • Gene therapy
  • Immune-checkpoint
  • PD-1

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