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

doi:10.3390/ijms19020340

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 journal › Review article › peer-review

120 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 language	English (US)
Article number	340
Journal	International journal of molecular sciences
Volume	19
Issue number	2
DOIs	https://doi.org/10.3390/ijms19020340
State	Published - 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.

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms19020340

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855562

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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.",

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

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

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