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Treatment of EGFR over-expressing cancers by targeted non-viral delivery of PolyIC

Objective

We have recently shown that application of EGFR targeted synthetic dsRNA: Poly Iosine/Poly Cytosine (pIC) is highly efficient and selective against deadly cancers overexpressing EGFR, like glioblastoma (U87MGwtEGFR), breast cancer (MDA-MB-468) and adenocarcinoma (A431). Double-stranded RNA, frequently expressed in cells infected with viruses, activates a number of pro-apoptotic processes simultaneously. These dsRNA-induced mechanisms efficiently kill infected cells and induce expression of anti-proliferative cytokines from the interferon (IFN) family, thereby preventing spread of the virus. pIC delivered with Melittin-polyethylenimine-polyethyleneglycol-EGF (MPPE) eliminated orthotropic and subcutaneous tumors of the above cancers. Heterogeneous glioblastoma models where only half of the cells overexpress wtEGFR are also eliminated by local application, most likely due to a bystander antiproliferative effects, at least partially mediated by interferons (Shir et al., 2006). Systemic application of EGFR targeted pIC is also highly effective against breast and adenocarcinoma disseminated cancer models resembling metastatic cancers (Shir et al., 2011). During the last two years we have improved the vectors homing to EGFR to entities that can now be translated into clinical agents (Shaffert, 2011; Shir 2011, Abourbeh 2012). The impressive results with these more simplified vectors, make this project ready for clinical development, which requires fund raising from a Company/Venture capitalist. Commercialization of the therapy will be detailed in the proposal.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/rna
  • /medical and health sciences/clinical medicine/cancer/breast cancer
  • /medical and health sciences/clinical medicine/cancer

Call for proposal

ERC-2014-PoC
See other projects for this call

Funding Scheme

ERC-POC - Proof of Concept 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
€ 150 000

Beneficiaries (1)

THE HEBREW UNIVERSITY OF JERUSALEM
Israel
EU contribution
€ 150 000
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Activity type
Higher or Secondary Education Establishments