title: Generation of V α13/β21+T cell specific target CML cells by TCR gene transfer.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, China.|Institute of Hematology, Jinan University, Guangzhou, China.|Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zha
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.|Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma
keywords: T cell receptor; chronic myeloid leukemia; gene transfer; immunotherapy