1. ¹Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China
2. ²Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China
3. ³Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
4. ⁴Laboratory of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China

Correspondence: Dr J-N Zheng, Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu 221002, China. E-mail: jnzheng@xzmc.edu.cn

⁵These authors contributed equally to this work.

Received 22 August 2008; Revised 27 December 2008; Accepted 19 February 2009; Published online 5 June 2009.

Abstract

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.