Oncolytic adenovirus expressing interleukin-18 induces significant antitumor effects against melanoma in mice through inhibition of angiogenesis

Cancer Gene Ther. 2010 Jan;17(1):28-36. doi: 10.1038/cgt.2009.38.


It has been shown that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in tumor cells. ZD55-IL-18 significantly decreased vascular endothelial growth factor and CD34 expression in the melanoma cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP (enhanced green fluorescent protein) or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity through inhibition of angiogenesis and offer a novel approach to melanoma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Adenoviridae / physiology*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Genetic Therapy / methods
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / genetics*
  • Male
  • Melanoma / therapy*
  • Melanoma / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / therapy
  • Neovascularization, Pathologic / virology
  • Oncolytic Virotherapy / methods*
  • Xenograft Model Antitumor Assays


  • Interleukin-18