title: PolyIC GE11 polyplex inhibits EGFR-overexpressing tumors.
abstract: Phage display has identified the dodecapeptide YHWYGYTPQNVI (GE11) as a ligand that binds to the epidermal growth factor receptor (EGFR) but does not activate the receptor. Here, we compare the EGFR binding affinities of GE11, EGF, and their polyethyleneimine-polyethyleneglycol (PEI-PEG) conjugates. We found that although GE11 by itself does not exhibit measurable affinity to the EGFR, tethering it to PEI-PEG increases its affinity markedly, and complex formation with polyinosine/cytosine (polyIC) further enhances the affinity to the submicromolar range. PolyIC/PPGE11 has a similar strong antitumor effect against EGFR overexpressing tumors in vitro and in vivo, as polyIC/polyethyleneimine-polyetheleneglycol-EGF (polyIC/PP-EGF). Absence of EGFR activation, as previously shown by us and easier production of GE11 and GE11 conjugates, confer polyIC/PPGE11 a significant advantage over similar EGF-based polyplexes as a potential therapy of EGFR overexpressing tumors.
authors.affiliation: Cyclotron/Radiochemistry Unit/Nuclear Medicine Department, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Galith
authors.initials: G
authors.lastname: Abourbeh
authors.forename: Alexei
authors.initials: A
authors.lastname: Shir
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
authors.forename: Manfred
authors.initials: M
authors.lastname: Ogris
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rödl
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
authors.forename: Alexander
authors.initials: A
authors.lastname: Levitzki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage*; D011070:Poly I-C / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
chemical_list: C572557:GE11 peptide; D008024:Ligands; D010455:Peptides; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D011094:Polyethyleneimine; D066246:ErbB Receptors; D011070:Poly I-C