Generation of V α13/β21+T cell specific target CML cells by TCR gene transfer
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Xianfeng Zha1,2,3, Ling Xu2, Shaohua Chen2, Lijian Yang2, Yikai Zhang2, Yuhong Lu4, Zhi Yu4, Bo Li2, Xiuli Wu2, Wenjie Zheng3, Yangqiu Li2,4,5
1Department of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, China
2Institute of Hematology, Jinan University, Guangzhou, China
3Department of Chemistry, Jinan University, Guangzhou, China
4Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China
5Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China
Yangqiu Li, email: [email protected]
Keywords: chronic myeloid leukemia, T cell receptor, gene transfer, immunotherapy
Received: May 02, 2016 Accepted: September 13, 2016 Published: October 04, 2016
Adoptive immunotherapy with antigen-specific T cells can be effective for treating melanoma and chronic myeloid leukemia (CML). However, to obtain sufficient antigen-specific T cells for treatment, the T cells have to be cultured for several weeks in vitro, but in vitro T cell expansion is difficult to control. Alternatively, the transfer of T cell receptors (TCRs) with defined antigen specificity into recipient T cells may be a simple solution for generating antigen-specific T cells. The objective of this study was to identify CML-associated, antigen-specific TCR genes and generate CML-associated, antigen-specific T cells with T cell receptor (TCR) gene transfer. Our previous study has screened an oligoclonal Vβ21 with a different oligoclonal Vα partner in peripheral blood mononuclear cells (PBMCs) derived from patients with CML. In this study, oligoclonally expanded TCR α genes, which pair with TCR Vβ21, were cloned into the pIRES eukaryotic expression vector (TCR Vα-IRES-Vβ21). Next, two recombinant plasmids, TCR Vα13-IRES-Vβ21 and TCR Vα18-IRES-Vβ21, were successfully transferred into T cells, and the TCR gene-modified T cells acquired CML-specific cytotoxicity with the best cytotoxic effects for HLA-A11+ K562 cells observed for the TCR Vα13/Vβ21 gene redirected T cells. In summary, our data confirmed TCRVα13/Vβ21 as a CML-associated, antigen-specific TCR. This study provided new evidence that genetically engineered antigen-specific TCR may become a druggable approach for gene therapy of CML.
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