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

Ling Feng He, Jin Fa Gu, Wen Hao Tang, Jun Kai Fan, Na Wei, Wei Guo Zou, Yan Hong Zhang, Li Li Zhao, Xin Yuan Liu

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)983-992
Number of pages10
JournalJournal of Gene Medicine
Volume10
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Keywords

  • Hepatocellular carcinoma
  • Interferon -β
  • Oncolytic adenovirus
  • Targeting gene-virotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

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