Objective We have recently shown that EGFR over-expressing tumors can be eradicated by an EGFR homing chemical vector, carrying dsRNA. The vector is PolyInosine/Cytosine (PolyIC) bound to Polyethleneimine-Polyethyleneglycol-EGF (PEI-PEG-EGF, PPE). We have shown that even tumors in which up to 50% of cells do not express EGFR are eradicated, due to the strong tumor-localized bystander effects, which involve the innate immune system. Using this EGFR homing vector we have been able to eradicate EGFR overexpressing tumors by either local or systemic application. Since the success of this strategy seems to be due to the strong bystander effects induced by the internalized PolyIC it is likely that heterogeneous tumors, in which only a portion of the cells harbor the targeted receptor, will be eradicated too, as shown in our preliminary studies (PloS Med, 2006). This strategy actually targets the innate immune system to the tumor. We propose to establish tumors in which decreasing portions of cells over-express EGFR and determine the lowest number of EGFR over-expressing cells that can yield tumor eradication by the lowest dose of PolyIC/PPE. The principle behind the success of the Trojan horse approach is that the targeting moiety, EGF, is tethered to the other components of the vector in such a way that it retains its native EGFR binding properties and its ability to internalize with the receptor. The composition of the vector is such that the ligand EGF can be replaced by any other ligand, if the appropriate coupling conditions are used, retaining the ability of the ligand to bind to the target protein and internalize with it. We propose to replace EGF by a number of other ligands, such PSMA binding ligand (targeting prostate cancer) and Her-2 affibodies. Although only a fraction of women who over-express Her-2 respond to Herceptin, it is likely that they will respond to PolyIC/PP-Her-2 affibody. Fields of science medical and health sciencesclinical medicineoncologyprostate cancernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2009-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution THE HEBREW UNIVERSITY OF JERUSALEM EU contribution € 2 054 340,00 Address EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Israel See on map Activity type Higher or Secondary Education Establishments Administrative Contact Hani Ben-Yehuda (Mr.) Principal investigator Alexander Levitzki (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE HEBREW UNIVERSITY OF JERUSALEM Israel EU contribution € 2 054 340,00 Address EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem See on map Activity type Higher or Secondary Education Establishments Administrative Contact Hani Ben-Yehuda (Mr.) Principal investigator Alexander Levitzki (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
