Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

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 b...

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Bibliographic Details
Main Authors:	Dok Hyun Yoon, Mark J. Osborn, Jakub Tolar, Chong Jai Kim
Format:	Article
Language:	English
Published:	MDPI AG 2018-01-01
Series:	International Journal of Molecular Sciences
Subjects:	adoptive T cell therapy chimeric antigen receptors PD-1 immune-checkpoint cancer immunotherapy gene editing gene therapy CRISPR/Cas9
Online Access:	http://www.mdpi.com/1422-0067/19/2/340

id	doaj-2576f88b9bb14a9a8b7972ec9d34a92f
record_format	Article
spelling	doaj-2576f88b9bb14a9a8b7972ec9d34a92f2020-11-24T20:48:16ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-01-0119234010.3390/ijms19020340ijms19020340Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-TDok Hyun Yoon0Mark J. Osborn1Jakub Tolar2Chong Jai Kim3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN 55455, USAAsan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN 55455, USAAsan-Minnesota Institute for Innovating Transplantation, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaChimeric 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.http://www.mdpi.com/1422-0067/19/2/340adoptive T cell therapychimeric antigen receptorsPD-1immune-checkpointcancer immunotherapygene editinggene therapyCRISPR/Cas9
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Dok Hyun Yoon Mark J. Osborn Jakub Tolar Chong Jai Kim
spellingShingle	Dok Hyun Yoon Mark J. Osborn Jakub Tolar Chong Jai Kim Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T International Journal of Molecular Sciences adoptive T cell therapy chimeric antigen receptors PD-1 immune-checkpoint cancer immunotherapy gene editing gene therapy CRISPR/Cas9
author_facet	Dok Hyun Yoon Mark J. Osborn Jakub Tolar Chong Jai Kim
author_sort	Dok Hyun Yoon
title	Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T
title_short	Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T
title_full	Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T
title_fullStr	Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T
title_full_unstemmed	Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T
title_sort	incorporation of immune checkpoint blockade into chimeric antigen receptor t cells (car-ts): combination or built-in car-t
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1422-0067
publishDate	2018-01-01
description	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.
topic	adoptive T cell therapy chimeric antigen receptors PD-1 immune-checkpoint cancer immunotherapy gene editing gene therapy CRISPR/Cas9
url	http://www.mdpi.com/1422-0067/19/2/340
work_keys_str_mv	AT dokhyunyoon incorporationofimmunecheckpointblockadeintochimericantigenreceptortcellscartscombinationorbuiltincart AT markjosborn incorporationofimmunecheckpointblockadeintochimericantigenreceptortcellscartscombinationorbuiltincart AT jakubtolar incorporationofimmunecheckpointblockadeintochimericantigenreceptortcellscartscombinationorbuiltincart AT chongjaikim incorporationofimmunecheckpointblockadeintochimericantigenreceptortcellscartscombinationorbuiltincart
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Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

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