Identification using phage display of peptides promoting targeting and internalization into HPV-transformed cell lines

‘High‐risk’ human papilloma viruses (HPVs) cause cervical tumours. In order to treat these tumours therapeutic approaches must be developed that efficiently target the tumour cells. Using phage display, we selected tumour‐targeting peptides from a library of constrained nonamer peptides presented multivalently on pVIII of M13. Three different consensus peptide sequences were isolated by biopanning on HPV16‐transformed SiHa cells. The corresponding phage‐peptides targeted and were internalized in HPV16 transformed SiHa and CaSki cells as well as in HPV18‐transformed HeLa cells, but failed to bind a panel of normal or transformed cell lines. Two of the three selected peptides targeted cells only when presented on phage particles in a constrained conformation. However, all three peptides retained their targeting capacity when presented on the reporter protein enhanced green fluorescent protein (EGFP) in a monovalent form. These peptides may be useful for the design of drug or gene delivery vectors for the treatment of cervical cancer. Copyright © 2004 John Wiley & Sons, Ltd.