Adenovirus Targeting to Prostate-specific Membrane Antigen through Virus-displayed Semi-random Peptide Library Screening.

Cancer research 2010 Jul 29; In press

Wu P, Kudrolli T TA, Chowdhury W WH, Liu M MM, Rodriguez R, Lupold S SE

Department of Urology, Johns Hopkins University School of Medicine.

The convergence of phage-displayed peptide libraries and recombinant viral vectors launched a promising new direction in targeted viral gene therapeutics, but the translation of targeting peptides to functional cancer therapeutic agents has been challenging. Here we report progress in developing a successful strategy to optimize targeted viral infection through adenovirus-displayed semi-random peptide libraries. A phage-derived peptide targeting the Prostate Specific Membrane Antigen (PSMA) was genetically incorporated into the adenoviral capsid Fiber protein and flanked by random peptide cassettes. The resulting adenovirus library was biopanned against PSMA-expressing cells and tumors to identify a PSMA-retargeted adenovirus. While the initial peptide alone was unable to target viral infection, the selected virus preferentially infects PSMA-expressing cells through the targeting peptide and infects LNCaP tumors after intravenous injection. Our results indicate that virus-displayed semi-random peptide libraries can be used to optimize targeting infection. This approach represents a novel principle for developing targeted agents in a variety of disease models.

Keywords: Adenovirus prostate cancer