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Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

Cancer Gene Therapy volume 12, pages 617–626 (2005)Cite this article

Abstract

Avian adenovirus CELO is a novel adenovirus vector system with the advantages of efficient production, high virion stability, and the absence of crossreactivity with Ad5-neutralizing antibodies. In this study, we evaluated the anticancer efficacy of a CELO vector encoding the herpes simplex virus type 1 thymidine kinase, a prodrug-activating therapeutic gene. Vectors carrying the gene for HSV-tk or EGFP under the control of the HCMV promoter in place of the “nonessential” region of the CELO genome were constructed. Anticancer activity of the CELO-TK vector was studied in vitro, in human and murine tumor cells in cell culture, and in vivo, in established subcutaneous murine B16 melanoma tumors in C57BL/6 mice. The CELO-TK vector mediated delivery of functional HSV-tk to tumor cell lines in cell culture. Comparison of the CELO-TK vector to a first-generation human adenovirus type 5 vector Ad5-TK in cultured H1299 cells showed equal levels of functional activity at increasing multiplicities of infection with CELO-based vector. CELO vectors allowed for transduction and expression of EGFP and HSV-tk genes in subcutaneous melanoma tumors in C57BL/6 mice. Intratumoral injections of CELO-TK followed by ganciclovir administration resulted in suppression of tumor growth and significantly increased the median of survival. The results of the study demonstrated the efficacy of CELO vector as a vehicle for the delivery of prodrug-activating genes such as HSV-tk to tumor cells in vitro and in vivo.

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Acknowledgements

We wish to thank Frank Graham, Valeri Krougliak, Matthew Cotten, Galina Deichman, and Maxim Shmarov for cell lines and reagents. We are thankful to Boris Naroditsky, Valeri Krougliak, Dmitry Shayakhmetov, and Alexander Zakhartchouk for helpful discussions, and to Denis Logunov for technical assistance. We are grateful to Drew L Lichtenstein for critical reading of the manuscript. The work was supported by grants 01-04-48454 from the Russian Foundation for Basic Research and CA105841 from the National Institutes of Health to KD.

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Authors and Affiliations

  1. Institute of Agricultural Biotechnology, Timiryazevskaya St. 42, Moscow, 127550, Russia

    Elena V Shashkova

  2. Gamaleya Research Institute of Epidemiology and Microbiology, Gamaleya St. 18, Moscow, 123098, Russia

    Lubov V Cherenova

  3. Institute of Carcinogenesis, Blokhin Cancer Research Center, Kashirskoe Sh. 24, Moscow, 115487, Russia

    Dmitry B Kazansky

  4. Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Blvd., St Louis, Missouri, 63104, USA

    Konstantin Doronin

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  1. Elena V Shashkova
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Correspondence to Konstantin Doronin.

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Shashkova, E., Cherenova, L., Kazansky, D. et al. Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors. Cancer Gene Ther 12, 617–626 (2005). https://doi.org/10.1038/sj.cgt.7700822

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