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

TitleIncorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells
Authors
KeywordsCD4+ T cell
CD19
CAR T cell
Mesothelin
Hinge domain
Expansion
Issue Date2017
Citation
Journal of Hematology and Oncology, 2017, v. 10, n. 1 How to Cite?
Abstract© 2017 The Author(s). 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.
Persistent Identifierhttp://hdl.handle.net/10722/249157
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorQin, Le-
dc.contributor.authorLai, Yunxin-
dc.contributor.authorZhao, Ruocong-
dc.contributor.authorWei, Xinru-
dc.contributor.authorWeng, Jianyu-
dc.contributor.authorLai, Peilong-
dc.contributor.authorLi, Baiheng-
dc.contributor.authorLin, Simiao-
dc.contributor.authorWang, Suna-
dc.contributor.authorWu, Qiting-
dc.contributor.authorLiang, Qiubin-
dc.contributor.authorLi, Yangqiu-
dc.contributor.authorZhang, Xuchao-
dc.contributor.authorWu, Yilong-
dc.contributor.authorLiu, Pentao-
dc.contributor.authorYao, Yao-
dc.contributor.authorPei, Duanqing-
dc.contributor.authorDu, Xin-
dc.contributor.authorLi, Peng-
dc.date.accessioned2017-10-27T05:59:15Z-
dc.date.available2017-10-27T05:59:15Z-
dc.date.issued2017-
dc.identifier.citationJournal of Hematology and Oncology, 2017, v. 10, n. 1-
dc.identifier.urihttp://hdl.handle.net/10722/249157-
dc.description.abstract© 2017 The Author(s). 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.-
dc.languageeng-
dc.relation.ispartofJournal of Hematology and Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCD4+ T cell-
dc.subjectCD19-
dc.subjectCAR T cell-
dc.subjectMesothelin-
dc.subjectHinge domain-
dc.subjectExpansion-
dc.titleIncorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13045-017-0437-8-
dc.identifier.scopuseid_2-s2.0-85015245388-
dc.identifier.volume10-
dc.identifier.issue1-
dc.identifier.spagenull-
dc.identifier.epagenull-
dc.identifier.eissn1756-8722-
dc.identifier.isiWOS:000396790900001-

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