title: Significant antitumor activity of oncolytic adenovirus expressing human interferon-beta for hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Laboratory of Cancer Therapy, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ling Feng
authors.initials: LF
authors.lastname: He
authors.forename: Jin Fa
authors.initials: JF
authors.lastname: Gu
authors.forename: Wen Hao
authors.initials: WH
authors.lastname: Tang
authors.forename: Jun Kai
authors.initials: JK
authors.lastname: Fan
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.forename: Wei Guo
authors.initials: WG
authors.lastname: Zou
authors.forename: Yan Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Li Li
authors.initials: LL
authors.lastname: Zhao
authors.forename: Xin Yuan
authors.initials: XY
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017930:Genes, Reporter; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D014765:Viral Vaccines; D023041:Xenograft Model Antitumor Assays
chemical_list: D014765:Viral Vaccines; C464532:dl1520; D016899:Interferon-beta