title: Identification of Vβ7.1_H3F7 as a therapeutic gene encoding TCR specific to hepatocellular carcinoma.
abstract: The feasibility of T-Cell receptor (TCR) gene therapy using a MART-1-specific TCR has been previously demonstrated in melanoma patients. However, it remains a challenge without a defined tumor-specific antigen in the therapy of hepatocellular carcinoma (HCC). In this study, through the analysis of clonal expansion of TCR Vβ subfamily and DNA sequencing, we identified TCR Vβ7.1_H3F7 as a potential therapeutic gene specifically for the HCC patients. Peripheral blood monouclear cells (PBMC) transfected with TCRV β7.1_H3F7 gene were specifically cytotoxic against HCC cells in vitro. Adoptive transfer of this transfected PBMC resulted in a marked suppression of HCC tumor development in the animal model. These results demonstrated the value of TCRV β7.1_H3F7 as a therapeutic gene specifically for HCC. More importantly, it provides a novel strategy for screening tumor-specific TCR genes, which may pave the way for TCR gene therapy in cancer patients currently without the defined tumor-specific antigens.
authors.forename: Shulin
authors.initials: S
authors.lastname: Huang
authors.forename: Han
authors.initials: H
authors.lastname: Shen
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.forename: Sung-Kay
authors.initials: SK
authors.lastname: Chiu
authors.forename: Runsheng
authors.initials: R
authors.lastname: Ruan
authors.forename: Lanfeng
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, 361102 Xiamen, P.R. China. cmtzeng@xmu.edu.cn.
authors.forename: Chi-Meng
authors.initials: CM
authors.lastname: Tzeng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation*; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell