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

2004; Wiley; Volume: 18; Issue: 2 Linguagem: Inglês

10.1002/jmr.723

1099-1352

Philip Robinson, Denise Stuber, François Deryckère, Philip R. Tedbury, Magali Lagrange, Georges Orfanoudakis,

Virus-based gene therapy research

‘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.