Identification of V beta 7.1_H3F7 as a Therapeutic Gene Encoding TCR Specific to Hepatocellular Carcinoma

Authors：Huang Shulin; Shen Han; Li Zhiming; Chiu Sung Kay; Ruan Runsheng; Xiao Lanfeng; Tzeng Chi Meng^*

Source：Current Gene Therapy, 2014, 14(5): 389-399.

DOI：10.2174/1566523214666140825124733

• Hepatocellular carcinoma
• TCR
• TCR V beta 7.1_H3F7
• therapeutic gene

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 V beta subfamily and DNA sequencing, we identified TCR V beta 7.1_H3F7 as a potential therapeutic gene specifically for the HCC patients. Peripheral blood monouclear cells (PBMC) transfected with TCRV beta 7.1_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 beta 7.1_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.

• Institution
  广东药学院; 香港城市大学; 厦门大学