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Antitumor effects on human melanoma xenografts of an amplicon vector transducing the herpes thymidine kinase gene followed by ganciclovir

Cancer Gene Therapy volume 9, pages 1–8 (2002)Cite this article

Abstract

Herpes simplex virus type-1 (HSV-1) has been demonstrated as a potentially useful gene delivery vector for gene therapy due to its high efficiency of in vivo transduction. The helper virus–dependent, HSV-1 amplicon vectors were developed for easier operation and their larger capacity. In this study, the herpes simplex virus type-1 thymidine kinase (HSVtk) gene was cloned into the pHE700 amplicon vector to make an HE7tk vector and used for in vivo gene delivery. Human melanoma xenografts were established in athymic nude mice. Tumors were injected directly with HE7tk vector alone, HE7tk vector followed by ganciclovir (GCV), or a pHE700 amplicon vector carrying a green fluorescent protein (HE7GFP) gene followed by GCV. Efficient HSVtk transgene expression was found in the tumor 3 days after injection. Animals transduced with HE7tk followed by GCV had minimal tumor growth (P<.01). Animals that received either HE7tk vector without GCV or HE7GFP vector with GCV had some reduction in tumor growth compared to animals that were injected with buffer only. These data indicate that replication-defective HSV-1 amplicon vectors can be used effectively to deliver transgenes into solid tumors in vivo.

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Acknowledgements

We thank D Hellrung for help in statistical analysis and NVahanian for manuscript review. We thank J Wang for technical assistance, N DeLucca for the E5 cell line, and PJohnson for the CgalΔ3 virus. This work was supported by the American Cancer Society Grant RPG-98-091-01-MBC.

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Authors and Affiliations

  1. Human Gene Therapy Research Institute, John Stoddard Cancer Center, Iowa Methodist Medical Center, Des Moines, 50309, Iowa, USA

    Suming Wang, Jianguo Qi, Michael Smith & Charles J Link

  2. Department of Histology and Embryology, West China University of Medical Sciences, Chengdu, 610041, Sichuan, China

    Jianguo Qi

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  1. Suming Wang
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  2. Jianguo Qi
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Correspondence to Charles J Link.

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Wang, S., Qi, J., Smith, M. et al. Antitumor effects on human melanoma xenografts of an amplicon vector transducing the herpes thymidine kinase gene followed by ganciclovir. Cancer Gene Ther 9, 1–8 (2002). https://doi.org/10.1038/sj.cgt.7700402

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