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Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

Gene Therapy volume 8, pages 946–953 (2001)Cite this article

Abstract

Replication-incompetent adenoviruses (Ad) carrying the herpes simplex thymidine kinase (HSVtk) gene have been used in a number of human cancer gene therapy trials, however transduction has generally been limited to a small minority of tumor cells. To solve this problem, replication-competent adenoviral vectors carrying transgenes such as HSVtk have been developed. However, contradictory evidence exists regarding the efficacy of these new vectors. Accordingly, we constructed and tested a replication-competent E3-deleted adenoviral vector containing the HSVtk suicide gene driven by the endogenous E3 promoter (Ad.wt.tk). This virus showed high level production of the HSVtk transgene and was more efficacious than a non-replicating virus in vitro, after injection into flank tumors, and against established intraperitoneal tumors. However, addition of ganciclovir (GCV) therapy to cells or tumor-bearing animals treated with the replicating vector containing the HSVtk suicide gene did not result in increased cell killing. Our results indicate that addition of HSVtk to a replicating Ad virus will not likely be useful in augmenting antitumor effects.

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Acknowledgements

This research was supported by grants from the National Cancer Institute (NCI PO1 66726 and SPORE grant P50-CA-83638) and support provided by the Benjamin Shein Foundation for Humanity. RW is a postdoctoral fellow of the Mildred Scheel Stiftung für Krebsforschung der Deutschen Krebshilfe e.V. (D/98/02288).

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  1. ES Lambright and K Amin: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    ES Lambright, K Amin, SD Force, M Lanuti & LR Kaiser

  2. Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    R Wiewrodt & SM Albelda

  3. Department of Biostatistics, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    KJ Propert

  4. Department of Pathology, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    L Litzky

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  1. ES Lambright
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  2. K Amin
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  3. R Wiewrodt
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Lambright, E., Amin, K., Wiewrodt, R. et al. Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy. Gene Ther 8, 946–953 (2001). https://doi.org/10.1038/sj.gt.3301489

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  • DOI: https://doi.org/10.1038/sj.gt.3301489

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