Combination of cytosine deaminase suicide gene expression with DR5 antibody treatment increases cancer cell cytotoxicity.

摘要: Combined treatment using adenoviral-directed enzyme/prodrug therapy and immunotherapy has the potential to become a powerful alternative method of cancer therapy. We have developed adenoviral vectors encoding cytosine deaminase gene (Ad-CD) deaminase:uracil phosphoribosyltransferase fusion (Ad-CD:UPRT). A monoclonal antibody, TRA-8, specifically binds death receptor 5, one two receptors bound by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The purpose this study was evaluate cytotoxicity in vitro therapeutic efficacy vivo combination Ad-CD:UPRT TRA-8 against human pancreatic glioma cell lines. present demonstrates that infection resulted increased 5-FC-mediated killing, compared with Ad-CD. Furthermore, significant increase following Ad-CD:UPRT/5-FC cells demonstrated. Animal studies showed inhibition growth MIA PaCa-2 D54MG xenografts plus as either agent alone or no treatment. results suggest produces an additive cytotoxic effect vivo. These data indicate combined TRAIL provides promising approach for