RESEARCH ARTICLE A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents

Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel condi-tionally replicating adenovirus targeting multiple receptors upregulated on tumors was gen-erated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in all tumor lines assayed at low titers with improved cytotox-icity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was then engi-neered to deliver immunotherapeutic agents such as GM-CSF while maintaining enhanced heterogenic oncolysis