591. Comparison of Plant-TK/AZT Versus HSV-TK/Ganciclovir Enzyme/Prodrug Systems in a Human Glioma Cell Line

Abstract

Nucleoside analogs were among the first chemotherapeutic agents to be used for the medical treatment of malignant and viral diseases. Although these compounds are used as first line therapy for many cancer types, several disadvantages still remain. Therefore alternative strategies like gene therapy are being developed to improve their therapeutic properties. There are many barriers to overcome in developing clinically useful suicide therapy systems. Effective tumor destruction depends on the chemistry of the prodrugs, the interaction between enzyme and prodrug, and the choice of the gene therapy vector. The perfect prodrug should be rapidly activated, so issues like prodrug half-life, degradation or clearance mechanisms will not be limiting factors. On the other hand, highly efficient enzymes should prove beneficial since gene expression and gene transfer are usually not high in vivo. Because current delivery methods cannot transfer the gene to all tumor cells, the strong bystander effect, where activated prodrug can kill neighboring tumor cells that are not expressing the suicide gene, is also needed.