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

Background Human interferon-beta (IFN-beta) 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-beta was constructed in this study. Methods The oncolytic adenoviruses were generated by homologous recombination in packaging cells. The expression of the IFN-beta protein was detected by enzyme-linked immunosorbent assay (ELISA). The antitumor efficacy of ZD55-IFN-beta was evaluated in cell lines and human hepatocellular carcinoma xenografts in nude mice. Results ZD55-IFN-beta can express much more IFN-beta than Ad-IFN-beta because of the replication of the ZD55 vector. Our data showed that ZD55-IFN-beta could exert a strong cytopathic effect on tumor cells (about 100-fold higher than Ad-IFN-beta or ONYX-015). Moreover, no obvious cytotoxic or apoptotic effects were detected in normal cells infected with ZD55-IFN-beta. Conclusions The antitumor efficacy of IFN-beta could be significantly improved due to the increased gene expression level from the tumor-selective replicating vector. The oncolytic adenovirus expressing IFN-beta may provide a novel approach for cancer gene therapy. Copyright (C) 2008 John Wiley & Sons, Ltd.