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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Rapid communication

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

Authors: Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li

Published in: Journal of Hematology & Oncology | Issue 1/2017

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Abstract

Background

Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined.

Methods

We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo.

Results

During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of CD4+ CAR T cell expansion, regardless of the single-chain variable fragment (scFv). In vitro migration assay showed that the hinges enhanced CAR T cells migratory capacity. The T cells expressing anti-CD19 CARs with or without a hinge had similar antitumor capacities in vivo, whereas the T cells expressing anti-mesothelin CARs containing a hinge domain showed enhanced antitumor activities.

Conclusions

Hence, our results demonstrate that a hinge contributes to CAR T cell expansion and is capable of increasing the antitumor efficacy of some specific CAR T cells. Our results suggest potential novel strategies in CAR vector design.
Appendix
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Metadata
Title
Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells
Authors
Le Qin
Yunxin Lai
Ruocong Zhao
Xinru Wei
Jianyu Weng
Peilong Lai
Baiheng Li
Simiao Lin
Suna Wang
Qiting Wu
Qiubin Liang
Yangqiu Li
Xuchao Zhang
Yilong Wu
Pentao Liu
Yao Yao
Duanqing Pei
Xin Du
Peng Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0437-8

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