Significant antitumor activity of oncolytic adenovirus expressing human interferon-β for hepatocellular carcinoma

Background: Human interferon-β (IFN-β) has been widely used in gene therapy for its antitumor activity but its therapeutic effect is limited. The conditionally replicative adenovirus ONYX-015 (a E1B-55-kDa-deleted adenovirus) targets well to tumor cells, but is not potent enough to cause significant tumor regression. To solve these problems, a tumor-selective replicating adenovirus expressing IFN-β was constructed in this study. Methods: The oncolytic adenoviruses were generated by homologous recombination in packaging cells. The expression of the IFN-β protein was detected by enzyme-linked immunosorbent assay (ELISA). The antitumor efficacy of ZD55-IFN-β was evaluated in cell lines and human hepatocellular carcinoma xenografts in nude mice. Results: ZD55-IFN-β can express much more IFN-β than Ad-IFN-β because of the replication of the ZD55 vector. our data showed that ZD55-IFN-β could exert a strong cytopathic effect on tumor cells (about 100-fold higher than Ad-IFN-β or ONYX-015). Moreover, no obvious cytotoxic or apoptotic effects were detected in normal cells infected with ZD55-IFN-β. Conclusions: The antitumor efficacy of IFN-β could be significantly improved due to the increased gene expression level from the tumor-selective replicating vector. The oncolytic adenovirus expressing IFN-β may provide a novel approach for cancer gene therapy.