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

Lambright ES, Amin K, Wiewrodt R, Force SD, Lanuti M, Propert KJ, Litzky L, Kaiser LR, Albelda SM
Gene Ther. 2001 8 (12): 946-53

PMID: 11426335 · DOI:10.1038/sj.gt.3301489

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.

MeSH Terms (20)

Adenoviridae Analysis of Variance Animals Antiviral Agents Female Ganciclovir Genetic Therapy Genetic Vectors Injections, Intralesional Lung Neoplasms Male Mice Mice, Nude Mice, SCID Neoplasms, Experimental Neoplasm Transplantation Simplexvirus Thymidine Kinase Transduction, Genetic Virus Replication

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