1020. Development and Evaluation of a Genetically-Modified Adenovirus Vector That Specifically Targets Tumors Via the Bloodstream Following Systemic Administration

Abstract

The development of genetically modified adenovirus vectors capable of targeting tumors following systemic administration is an important goal for the treatment of disseminated cancer. Achieving this goal requires that the native adenovirus coat protein/receptor interactions are removed and replaced with new tumor-selective ligand/receptor interactions. Towards this goal, we have created vectors that are ablated for native receptor binding and that additionally contain a pseudo-receptor binding ligand or a tumor-selective peptide motif inserted into the HI loop of fiber. In vivo experiments showed that ablating both CAR and penton base binding is critical to reduce non-targeted tissue transduction. In addition, pharmacokinetic studies indicated that these tropism modified vectors efficiently enter and persist in the bloodstream following intraperitoneal (i.p.) administration. Interestingly, this sustained circulation was only observed after i.p. administration and not after intravenous administration. Furthermore, the combination of capsid modification and extended blood circulation could achieve receptor-mediated transduction on pseudo-receptor expressing subcutaneous tumor.