Evaluation of Biodistribution of a Fiber-Chimeric, Conditionally Replication-Competent (Oncolytic) Adenovirus in CD46 Receptor Transgenic Mice

Abstract The limited efficacy of adenovirus type 5 (Ad5)-based oncolytic viruses seen in the clinic thus far may be attributable in part to variable expression of its receptor on tumor cells. Replacement of the Ad5 fiber knob with the Ad35 fiber knob generated the Ad5/35 chimeric virus, which has previously been demonstrated to have significant antitumor activity in murine tumor models, presumably by virtue of its recognition of the CD46 receptor, which is abundant on many types of tumor cells. In the current study, a CD46 receptor transgenic mouse strain (hCD46Ge) that expresses the CD46 receptor in a pattern closely mirroring that in humans was used to study the in vivo properties of Ad5/Ad35 chimeric viruses. Vector distribution was evaluated after intravenous administration to hCD46Ge mice of an Ad5-based oncolytic adenovirus or an Ad5/35 chimeric oncolytic adenovirus (designated OV-5 and OV-5T35H, respectively), a wild-type Ad5 virus (Ad5wt), or an Ad5-based, E1-deleted adenovirus (Addl312) at 1.25 ×...