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Basic study of gene therapy for hepatocellular carcinoma

肝细胞癌基因治疗的基础研究

基本信息

批准号：
07457133
负责人：
KOBAYASHI Kenichi
金额：
$ 4.29万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457133/
关键词：
gene therapy hepatocellular carcinoma retroviral vector herpes simplex thymidine kinase ganciclovir

项目摘要

Currently, clinical trials of suicide gene transfer with retroviral vector producer cells are being carried out for the treatment of brain tumors. The feasibility of applying this approach for the treatment of hepatocellular carcinoma is studied.Methods : Five hepatoma cell lines were tested for retroviral mediated transduction efficiency with the herpes simplex thymidine kinase (HSV-TK) gene and for the induced drug sensitivity to ganciclovir. Different populations of HSV-TK transduced HuH7 cells were subcutaneously injected into athymic nude mice with non transduced HuH7 cells to analyze the "bystander" effect. The retroviral vector producer cells were intratumorally injected into pre-established HuH7 tumors to study the antitumor effect.Results : Five hepatoma cell lines were transduced with the viral supernatant, and all resultant 50 transduced clones, except one, were sensitive to ganciclovir. Complete regression occurred in 21 out of 30 tumors when the inoculum consisted of as few as 10% of HSV-TK containing transduced cells. The producer cell injection into tumors and GCV treatment group was significantly smaller in size of the tumors compared to GCV treatment group (p<0.01).Conclusions : This gene therapy approach could potentially be effective for the treatment of human hepatocellular carcinoma.

目前，正在利用逆转录病毒载体生产细胞进行自杀基因转移治疗脑肿瘤的临床试验。研究了应用这种方法治疗肝细胞癌的可行性。方法：测试了五种肝癌细胞系的逆转录病毒介导的单纯疱疹胸苷激酶（HSV-TK）基因的转导效率以及对更昔洛韦诱导的药物敏感性。将不同群体的HSV-TK转导的HuH7细胞皮下注射到未转导的HuH7细胞的无胸腺裸鼠中，以分析“旁观者”效应。将逆转录病毒载体生产细胞瘤内注射到预先建立的HuH7肿瘤中以研究抗肿瘤作用。结果：用病毒上清转导5个肝癌细胞系，所得到的50个转导克隆除1个外均对更昔洛韦敏感。当接种物仅由 10% 的含有 HSV-TK 的转导细胞组成时，30 个肿瘤中有 21 个发生完全消退。与GCV治疗组相比，将生产细胞注射到肿瘤中并且GCV治疗组的肿瘤尺寸明显更小(p<0.01)。结论：这种基因治疗方法可能对人类肝细胞癌的治疗有效。