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

使用病毒的基因治疗似乎对癌症治疗有效，但由于病毒对整个癌细胞的递送效率较低，这种策略仍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survivin的启动子，其表达对癌细胞具有高度特异性。体外单步实验显示，SurvHSV-1在不表达survivin的成纤维细胞中无扩增。另一方面，在表达survivin的HT29或HepG2中发现了扩增，但其复制不足以杀死这些癌细胞。在体内研究中，病毒治疗转移性肝癌对表达survivin的Panc 1的生长有较好的抑制作用，但效果不如缺乏ICP6的重组HSV-1 hrR3。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，无法产生溶瘤作用。提高survivin启动子的活性可能会使这种治疗转移性肝癌的新方法更加有效。

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.