In vivo bacteriophage display for the discovery of novel peptide-based tumor-targeting agents.

Abstract

A powerful strategy for targeted drug discovery is the use of bacteriophage (phage) display technology for identification of peptide-based tumor targeting agents. Peptide pharmaceuticals may possess clinically desirable properties because of their rapid blood clearance, non-immunogenic nature, and ease of synthesis. Phage display has identified hundreds of different peptide sequences that bind a desired target in vitro. Regrettably, few of these peptides offer good targeting efficacy in vivo. One reason for this is the synthesized peptide may not retain its optimal activity outside the microenvironment of the phage. Another possible explanation is that traditionally, phage selections are performed in vitro outside the complicated milieu of a living animal. Given these shortcomings, we have developed methods to select phage peptide display libraries in living mice, to identify, a priori, phage (and corresponding synthesized peptides) with ideal tumor-targeting propensity.