ANGIOPOIETINS
Rational and Combinatorial Engineering of Antagonistic Angiopoietin Variants as Tools for Cancer Imaging and Therapy
| Coordinatore | BEN-GURION UNIVERSITY OF THE NEGEV
Organization address
address: Office of the President - Main Campus contact info |
| Nazionalità Coordinatore | Israel [IL] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2011-CIG |
| Funding Scheme | MC-CIG |
| Anno di inizio | 2012 |
| Periodo (anno-mese-giorno) | 2012-04-01 - 2016-03-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
BEN-GURION UNIVERSITY OF THE NEGEV
Organization address
address: Office of the President - Main Campus contact info |
IL (BEER SHEVA) | coordinator | 100˙000.00 |
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Obiettivo del progetto (Objective)
'The dysregulation of cell signaling pathways that mediate proliferation, survival, and migration is an underlying cause of many cancers. Dysregulation and over-expression of the Tie2 tyrosine kinase receptor, in particular, correlates to a poor prognosis for many human tumors, making Tie2 an attractive target for therapeutic intervention. Currently no FDA-approved therapeutics targeting the Tie2 receptor exist, and only a few candidate molecules are in early stage clinical trials. Moreover, development of Tie2-targeted molecular imaging agents for non-invasive visualization of Tie2 expression in vivo has been extremely limited compared to other cancer targets. Such imaging agents could help identify the best patient candidates for Tie2-targeted anti cancer therapies. Although ligand-based antagonists have opened up new research directions for generating new cancer biologics, limitations in ligand binding affinity, expression yield, and stability have prevented all but a few from advancing to clinical trials. The limited success of ligand-based antagonists motivates me to use modified Tie2-receptor agonists, i.e. angiopoietins, as a starting point from which to develop ligand-based antagonists. Angiopoietin antagonists will be created by introducing mutations into an angiopoietin that retains Tie2 binding but that prevents ligand multimerization and receptor dimerization and activation. Yeast-displayed angiopoietin mutant libraries will then be created and screened by high-throughput flow cytometric sorting to identify variants with increased expression and stability and affinity to Tie2. We will perform pre-clinical studies on the high affinity angiopoietin variants to determine their potential as in vivo molecular imaging agents and cancer therapeutics. In addition, we will fully characterize the binding and biological properties of the variants in both cell culture and pre-clinical solid and metastatic tumor models.'