Identification of Vβ7.1_H3F7 as a Therapeutic Gene Encoding TCR Specific to Hepatocellular Carcinoma
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.
Keywords: Hepatocellular carcinoma, TCR, TCR Vβ7.1_H3F7, therapeutic gene.
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