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Int. J. Mol. Sci. 2018, 19(2), 340; https://doi.org/10.3390/ijms19020340

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

1,2,3,4,†
,
3,4,5,6,7,†,* , 3,4,5,6,7
and
2
1
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
2
Asan-Minnesota Institute for Innovating Transplantation, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
3
Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN 55455, USA
4
Department of Pediatrics, University of Minnesota Medical School, Division of Blood and Marrow Transplantation, Minneapolis, MN 55455, USA
5
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
6
Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA
7
Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 29 December 2017 / Revised: 19 January 2018 / Accepted: 22 January 2018 / Published: 24 January 2018
(This article belongs to the Special Issue Chimeric Antigen Receptor (CAR) T Cell Therapy)
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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. View Full-Text
Keywords: adoptive T cell therapy; chimeric antigen receptors; PD-1; immune-checkpoint; cancer immunotherapy; gene editing; gene therapy; CRISPR/Cas9 adoptive T cell therapy; chimeric antigen receptors; PD-1; immune-checkpoint; cancer immunotherapy; gene editing; gene therapy; CRISPR/Cas9
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Yoon, D.H.; Osborn, M.J.; Tolar, J.; Kim, C.J. Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T. Int. J. Mol. Sci. 2018, 19, 340.

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