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

被引：159

作者：

Yoon, Dok Hyun ^{[1
,2
,3
,4
]}

Osborn, Mark J. ^{[3
,4
,5
,6
,7
]}

Tolar, Jakub ^{[3
,4
,5
,6
,7
]}

Kim, Chong Jai ^{[2
]}

机构：

[1] Univ Ulsan, Dept Oncol, Asan Med Ctr, Coll Med, Seoul 05505, South Korea

[2] Univ Ulsan, Asan Minnesota Inst Innovating Transplantat, Asan Inst Life Sci, Asan Med Ctr,Coll Med, Seoul 05505, South Korea

[3] Univ Minnesota, Asan Minnesota Inst Innovating Transplantat, Minneapolis, MN 55455 USA

[4] Univ Minnesota, Div Blood & Marrow Transplantat, Dept Pediat, Sch Med, Minneapolis, MN 55455 USA

[5] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA

[6] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA

[7] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

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

D O I：

10.3390/ijms19020340

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：16

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