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.
Robinson
Philip
P
UMR7100-CNRS Ecole Supérieure de Biotechnologie de Strasbourg, Université Louis Pasteur, boulevard Sébastien Brandt, 67400-Illkirch, France.
Stuber
Denise
D
Deryckère
François
F
Tedbury
Philip
P
Lagrange
Magali
M
Orfanoudakis
Georges
G
D001435:Bacteriophages / Q000378:metabolism; D002461:Cell Line, Transformed; D004705:Endocytosis / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000628:therapy / Q000821:virology; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D019151:Peptide Library; D014162:Transfection; D014407:Tumor Cells, Cultured
D008024:Ligands; D010446:Peptide Fragments; D019151:Peptide Library; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins