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Int J Mol Sci. 2018 Jan 24;19(2). pii: E340. doi: 10.3390/ijms19020340.

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

Yoon DH1,2,3,4, Osborn MJ5,6,7,8,9, Tolar J10,11,12,13,14, Kim CJ15.

Author information

1
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. dhyoon@amc.seoul.kr.
2
Asan-Minnesota Institute for Innovating Transplantation, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. dhyoon@amc.seoul.kr.
3
Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN 55455, USA. dhyoon@amc.seoul.kr.
4
Department of Pediatrics, University of Minnesota Medical School, Division of Blood and Marrow Transplantation, Minneapolis, MN 55455, USA. dhyoon@amc.seoul.kr.
5
Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN 55455, USA. osbor026@umn.edu.
6
Department of Pediatrics, University of Minnesota Medical School, Division of Blood and Marrow Transplantation, Minneapolis, MN 55455, USA. osbor026@umn.edu.
7
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. osbor026@umn.edu.
8
Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. osbor026@umn.edu.
9
Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. osbor026@umn.edu.
10
Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN 55455, USA. tolar003@umn.edu.
11
Department of Pediatrics, University of Minnesota Medical School, Division of Blood and Marrow Transplantation, Minneapolis, MN 55455, USA. tolar003@umn.edu.
12
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. tolar003@umn.edu.
13
Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. tolar003@umn.edu.
14
Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. tolar003@umn.edu.
15
Asan-Minnesota Institute for Innovating Transplantation, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. ckim@amc.seoul.kr.

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.

KEYWORDS:

CRISPR/Cas9; PD-1; adoptive T cell therapy; cancer immunotherapy; chimeric antigen receptors; gene editing; gene therapy; immune-checkpoint

PMID:
29364163
PMCID:
PMC5855562
DOI:
10.3390/ijms19020340
[Indexed for MEDLINE]
Free PMC Article

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