Identification of factors important for the success of suicide gene therapy after a comparative study of Varicella zoster and Herpes simplex viral thymidine kinases efficacy on breast cancer cells

Abstract

One of the most frequently studied therapeutic strategies in the field of suicide gene therapy is based on the expression by tumor cells of the Herpes simplex virus thymidine kinase gene (HSVtk) followed by a ganciclovir (GCV) treatment. In order to investigate the potential of other enzyme/prodrug strategies, we studied in vitro and in vivo the ability of the Varicella zoster virus thymidine kinase gene (VZVtk) to act as a suicide gene and to kill non-transduced bystander cells, and compared this activity to that of its HSV counterpart. Four different antiviral compounds were tested as prodrugs. Our comparative study demonstrates the superiority of the HSVtk/GCV system among the different combinations tested and underlines the importance of both the tumor cell type and the prodrug in the success of a prodrug/suicide gene strategy.