Tumor targeting with a selective gelatinase inhibitor

Several lines of evidence suggest that tumor growth, angiogenesis, and meta stasis are dependent on matrix metalloproteinase (MMP) activity, However, t he lack of inhibitors specific for the type IV collagenase/gelatinase famil y of MMPs has thus far prevented the selective targeting of MMP-2 (gelatina se A) and MMP-9 (gelatinase B) for therapeutic intervention in cancer, Here , we describe the isolation of specific gelatinase inhibitors from phage di splay peptide libraries. We show that cyclic peptides containing the sequen ce HWGF are potent and selective inhibitors of MMP-2 and MMP-9 but not of s everal other MMP family members, Our prototype synthetic peptide, CTTHWGFTL C, inhibits the migration of human endothelial cells and tumor cells, Moreo ver, it prevents tumor growth and invasion in animal models and improves su rvival of mice bearing human tumors. Finally, we show that CTTHWGFTLC-displ aying phage specifically target angiogenic blood vessels in vivo. Selective gelatinase inhibitors may prove useful in tumor targeting and anticancer t herapies.