PolyIC GE11 polyplex inhibits EGFR-overexpressing tumors.

IUBMB Life
Galith AbourbehAlexander Levitzki

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.

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Citations

Dec 5, 2013·Chemical Reviews·Bethany Powell Gray, Kathlynn C Brown
Oct 1, 2014·Journal of Pharmaceutical Sciences·Petra KosErnst Wagner
Mar 18, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mingliang FanBizhi Shi
Apr 16, 2015·Chemical Reviews·Ulrich Lächelt, Ernst Wagner
May 24, 2016·Advanced Drug Delivery Reviews·Ruiwu LiuKit S Lam
May 17, 2017·Advanced Drug Delivery Reviews·Ayelet David
Dec 23, 2017·Pharmaceutics·Ida GentaRossella Dorati
Jun 28, 2018·The Journal of Gene Medicine·Benjamin SteinbornWei Zhang
Oct 1, 2017·Bioscience Reports·Ana Krhac LevacicErnst Wagner
Jul 25, 2018·Amino Acids·Franziska StrieseHans-Jürgen Pietzsch
Sep 13, 2020·Cells·Simone HagerMatthias Bros
Apr 5, 2020·Advanced Drug Delivery Reviews·Franziska Freitag, Ernst Wagner
Nov 18, 2019·Molecular Therapy. Nucleic Acids·Alexander TaschauerManfred Ogris
May 4, 2021·Chemical Reviews·Ramya KumarTheresa M Reineke
Jul 29, 2017·ACS Chemical Neuroscience·Lizanne G NilewskiMartyn A Sharpe

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