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

Cancer Gene Therapy volume 17, pages 28–36 (2010)Cite this article

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.

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Abbreviations

EGFP:

enhanced green fluorescent protein

IL-18:

interleukin 18

MOI:

multiplicity of infection

TUNEL:

TdT-mediated dUTP-biotin nick end-labeling assay

VEGF:

vascular endothelial growth factor

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Acknowledgements

This project is supported by grants from the National Natural Science Foundation of China (No. 30700999), the Science and Technology Department of Jiangsu province (No. BK2006036) and the Program for New Century Excellent Talents in University (NCET-08-0700).

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Author notes

  1. J-N Zheng and D-S Pei: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China

    J-N Zheng, D-S Pei & B-F Zhang

  2. Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China

    J-N Zheng, L-J Mao, F-H Sun, J-J Liu, W Li & D Han

  3. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    X-Y Liu

  4. Laboratory of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China

    Y-Q Liu

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Correspondence to J-N Zheng.

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Zheng, JN., Pei, DS., Mao, LJ. et al. Oncolytic adenovirus expressing interleukin-18 induces significant antitumor effects against melanoma in mice through inhibition of angiogenesis. Cancer Gene Ther 17, 28–36 (2010). https://doi.org/10.1038/cgt.2009.38

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