Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

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Identification of Vβ7.1_H3F7 as a Therapeutic Gene Encoding TCR Specific to Hepatocellular Carcinoma

Author(s): Shulin Huang, Han Shen, Zhiming Li, Sung-Kay Chiu, Runsheng Ruan, Lanfeng Xiao, Chi-Meng Tzeng.

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.

Keywords: Hepatocellular carcinoma, TCR, TCR Vβ7.1_H3F7, therapeutic gene.

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Article Details

VOLUME: 14
ISSUE: 5
Year: 2014
Page: [389 - 399]
Pages: 11
DOI: 10.2174/1566523214666140825124733
Price: $58