a novel therapy for metastatic liver cancer using cancer specific replicating HSV-1

使用癌症特异性复制 HSV-1 治疗转移性肝癌的新疗法

• 批准号: 13671356
• 负责人: TOYODA Masao
• 金额: $ 2.5万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671356/
• 关键词: replicating HSV-1; survivin; cancer specific promoter; CEA; metastatic liver cancer; 増殖性組み換え型単純ヘルペス; 転移性肝癌

The gene therapy using virus seems to be efficient for cancer therapy, but this strategy still remains insufficient for complete remission of tumor due to the low efficiency of viral delivery to whole cancer cells. In this study, we established recombinant HSV-1 (SurvHSV-1) which replication is restricted to cancer cells. For this purpose, we used the promoter of survivin, which expression is high specific to cancer cell. In single step assay of in vitro, SurvHSV-1 shows no amplification in fibroblast, which doesn't express survivin. On the other hand, amplification was recognized in HT29 or HepG2, which express survivin, but its replication was not enough to kill those cancer cell. In vivo study, viral treatment for metastatic liver cancer showed good inhibition of growth of Panc 1 expressing survivin, but it is not so effective as hrR3, which is ICP6 deficient recombinant HSV-1. In summary, Surv HSV-1 can amplify specifically in cancer cell, but its replication is too small to have oncolytic effect. To improve the activity of survivin promoter should lead to be more effective in this novel therapy for metastatic liver cancer.

使用病毒的基因治疗似乎对癌症治疗有效，但由于病毒递送到整个癌细胞的效率低，这种策略仍然不足以完全缓解肿瘤。在这项研究中，我们建立了重组HSV-1（SurvHSV-1），其复制仅限于癌细胞。为此，我们使用了对癌细胞具有高度特异性表达的Survivin启动子。体外一步法检测SurvHSV-1在不表达Survivin的成纤维细胞中无扩增。另一方面，在表达存活素的HT 29或HepG 2中，扩增被识别，但其复制不足以杀死这些癌细胞。在体内研究中，转移性肝癌的病毒治疗显示出对表达存活素的Panc 1的生长的良好抑制，但其不如hrR 3（其是ICP 6缺陷型重组HSV-1）有效。综上所述，Surv HSV-1可以在癌细胞中特异性扩增，但其复制量太小，不具有溶瘤作用。提高survivin启动子的活性将有助于提高其在转移性肝癌治疗中的作用。