Virus-directed enzyme prodrug therapy using CB1954.

摘要: The virus-directed enzyme prodrug therapy (VDEPT) anti-cancer 'gene therapy' strategy relies on the use of viral vectors for efficient delivery to tumour cells a 'suicide gene' encoding an which converts non-toxic cytotoxic agent. 5-(aziridin-1-yl)-2,4 dinitrobenzamide, CB1954, has been proposed in enzyme-prodrug gene systems with Escherichia coli nitroreductase (Ntr). Ntr CB1954 2- and 4-hydroxylamino derivatives, whereupon non-enzymatic reaction derivative cellular thio- esters generates potent bifunctional alkylating agent capable cross-linking DNA. achieved vitro using retroviral adenoviral confirmed by immunocytochemical demonstration expression. Ntr-expressing have shown be sensitized up 2000-fold. Ntr-CB1954 system shows effective bystander killing mixed populations non-expressing treated CB1954. efficacy this approach model compared other VDEPT approaches demonstrates feasibility future promise strategy.