Coagulation factors determine tumor transduction in vivo

A critical obstacle for efficient gene therapy and virotherapy of cancer with adenoviral vectors and oncolytic adenoviruses is to target tumor cells in vivo. Recent reports indicate that, contrary to the natural airborne infection of epithelial cells with adenovirus type 5 mediated by coxsackievirus B and adenovirus receptor (CAR) and integrins, blood-borne adenovirus infects hepatocytes mainly through an indirect pathway that involves blood coagulation factors. In this report we have studied whether adenovirus also infects tumor cells in vivo by this pathway. In vitro and in vivo analyses show that vitamin K-dependent coagulation zymogens mediate tumor transduction and that the elimination of these factors abrogates tumor transduction. This finding imposes new challenges to retarget adenoviruses in vivo.