Skip to main content

Eradication of tumors by targeting dsRNA selectively to cancer cells and recruitment of the innate immune system

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.

Field of science

  • /medical and health sciences/basic medicine/immunology
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/cancer/prostate cancer

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
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 054 340
Principal investigator
Alexander Levitzki (Prof.)
Administrative Contact
Hani Ben-Yehuda (Mr.)

Beneficiaries (1)

THE HEBREW UNIVERSITY OF JERUSALEM
Israel
EU contribution
€ 2 054 340
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Activity type
Higher or Secondary Education Establishments
Principal investigator
Alexander Levitzki (Prof.)
Administrative Contact
Hani Ben-Yehuda (Mr.)