Novel cytotoxic conjugates of peptibodies targeting fibroblast growth factor receptors (FGFR)
The aim of this research project is to develop a new conjugate aimed at FGFR expressing cancer cells, based on FGFR-binding peptibody conjugated with a potent cytotoxic drug.
We plan to use two groups of FGFR-binding peptides. First group will consist of new, identified by us FGFR-binders derived from FGFR ligands sequences – FGFs. We will isolate binding regions from different members of FGF family and minimize these regions down to a set of linear peptides. The second group comprises of four peptides described in literature before, with confirmed ability to bind FGFR, but not yet tested in a peptibody format.
Developed FGFR-binding peptides will be then genetically fused to Fc (fragment crystallizable) region from IgG, forming peptibodies, which will be afterwards characterized in terms of their receptor-dependent internalization and their ability to inhibit FGF-induced activity. We
will validate this response on both FGFR-engineered cell lines and on model FGFR-positive and FGFR-negative cancer cell lines, with special emphasis put on FGFR-positive non-small cell lung carcinoma.
RESEARCH TEAM:
Anna Szlachcic (PhD) – project leader
Karolina Jendryczko (Msc) – PhD student
Natalia Skinder (Bsc) – student
Project is realized in a collaboration with the group of prof. Antoni Wiedlocha from Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
The „Novel cytotoxic conjugates of peptibodies targeting fibroblast growth factor receptors (FGFR) (POIR.04.04.00-00-5E53/18-00)” project is carried out within the POWROTY programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund.
Budget of the project: 799 160 PLN
Project duration: 11.2018 – 10.2020
CONTACT:
Anna Szlachcic (PhD)
Tel. +48 71375 2631