Antitumor Effects Of Selectively Oncolytic Adenovirus Vectors ZD55 Harboring Multisubstrate Deoxyribonucleoside Kinase Of Drosophila Melanogaster(Dm-dNK) In Colorectal Cancer

ObjectiveRecent studies showed that oncolytic adenoviruses not only have capacity for destruction of tumors but also can be used as potential vectors to express therapeutic genes for therapy of cancer. In this study, we combined the oncolytic potential of a CRAd with its ability to deliver a suicide gene (Dm-dNK) in order to further enhance tumor cell killingMehtodsWe constructed a CRAd adenoviral vector, which was designed by deletion of E1B-55 kDa gene for selective replication in tumor cells, containing suicide gene (Dm-dNK) driven by a cytomegalovirus promoter. Transgene expression, viral replication capacity, and cytotoxicity have been studied in tumor and normal cells. The safety of systemic admini-stration of the viruses was also evaluatedResultsThe ZD55-Dm-dNK delivered into the cell lines retained enzymatic activity, and the colorectal cancer cell lines showed increased sensitivity to nucleoside analogues, with time prolonged, enzymatical activity of Dm-dNK reached the maximal level at 5 days after infection in tumor cells. The enzymeatical activity was 51-58 times higher than that infected with ZD55 vector without Dm-dNK 5 days post-infection. Low level of Dm-dNK could be detected in normal cells only until 5 days after infection, strong cytotoxicity was observed only in tumor cells after infect-ion with ZD55-Dm-dNKConclusionsThis study shows that systemically delivered adenovirus harboring Dm-dNK which retained it's enzymatic activity, and phosphorylated nucleoside analogues. Use of Dm-dNK seems to be a potentially useful gene therapy for cancer. Our data showed that ZD55-Dm-dNk can provide potent and safe tool for the therapy of colon cancer...