The oncolytic adenovirus targeting to TERT and RB pathway induced specific and potent anti-tumor efficacy in vitro and in vivo for hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most difficult tumors to be treated. Overexpression of human telomerase reverse transcriptase (hTERT) and dysfunction of retinoblastoma (RB) have been implicated in HCC. Oncolytic viruses have been used as targeting therapy for different malignancies. In study, we have engineered oncolytic adenovirus to target both of TERT and RB pathways to achieve strict tumor specificity. Methods: A double-controlled recombinant adenovirus (AdCN103) was constructed by deletion of 24bp in CR2 region of E1A and replacement of E1A promoter with the modified hTERT promoter. As control vectors, we generated single-controlled recombinant adenovirus with either 24bp deleted E1A (AdCN101) or wild-type of E1A driven by hTERT promoter (AdCN102). Results: Our results showed that infection of HCC cell lines with AdCN101, AdCN102. or AdCN103 resulted in strong cytotoxicity. In contrast, there was a dramatic reduction of cytotoxicity in normal cells infected with AdCN102 and A...