摘要
使用MART-1特异性TCR基因治疗的可行性先前已在黑色素瘤患者中被证明。然而,在肝癌(HCC)治疗过程中,没有一个明确的肿瘤特异性抗原仍然是一个挑战。在这项研究中,通过TCR Vβ亚家族和DNA测序克隆扩增的分析,我们确定TCR Vβ7.1_H3F7可作为HCC患者的潜在特异性治疗基因。对于体外肝癌细胞,转染TCRVβ β7.1_H3F7基因的外周血单个核细胞(PBMC )有特异性细胞毒性。对这些转染外周血单个核细胞过继转移将导致动物模型中肝癌肿瘤的发展有显著的抑制。这些结果证明TCRV β7.1_H3F7可作为肝癌特异性治疗基因的价值。更重要的是,它提供了一种新的肿瘤特异性TCR基因的筛选策略,其可以作为目前在癌症患者中没有被界定的肿瘤特异性抗原的TCR基因疗法。
关键词: 肝细胞癌,T细胞受体 , TCR Vβ7.1_H3F7 ,治疗基因
Current Gene Therapy
Title:Identification of Vβ7.1_H3F7 as a Therapeutic Gene Encoding TCR Specific to Hepatocellular Carcinoma
Volume: 14 Issue: 5
Author(s): Shulin Huang, Han Shen, Zhiming Li, Sung-Kay Chiu, Runsheng Ruan, Lanfeng Xiao and Chi-Meng Tzeng
Affiliation:
关键词: 肝细胞癌,T细胞受体 , TCR Vβ7.1_H3F7 ,治疗基因
摘要: 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.
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Cite this article as:
Huang Shulin, Shen Han, Li Zhiming, Chiu Sung-Kay, Ruan Runsheng, Xiao Lanfeng and Tzeng Chi-Meng, Identification of Vβ7.1_H3F7 as a Therapeutic Gene Encoding TCR Specific to Hepatocellular Carcinoma, Current Gene Therapy 2014; 14 (5) . https://dx.doi.org/10.2174/1566523214666140825124733
DOI https://dx.doi.org/10.2174/1566523214666140825124733 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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