Abstract
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. Copyright © 2008 John Wiley & Sons, Ltd.