Informacja o projekcie



Highly cytotoxic FGF2-conjugates in targeted therapy for

FGFR-expressing cancers

 

Cancer treatment represents a crucial unmet need of current medicine. Particular emphasis is placed on targeted cancer therapies that are based on drugs that block the growth and spread of cancer cells by interfering with specific macromolecules, which are deregulated and play important role in tumor progression.

The main goal of this project is to develop a novel targeted therapy against different types of cancers overexpressing fibroblast growth factor receptors (FGFRs). We propose an unexplored approach based on the FGF2 molecule fused to a highly efficient cytotoxic drug to establish a delivery technique for effective killing of cancer cells. Our strategy is similar to construction of antibody drug conjugates (ADCs), which are showing clinical efficacy in cancer treatment. However, instead of antibodies we will use the engineered growth factor as a delivery molecule specifically directing cytotoxic drug to cancer cell by binding to FGF receptors.

 

Project presentation (pdf file)

 

Work Packages


1 Production and biophysical characterization of FGF2 and FGF2-conjugates for targeted therapy of FGFR-related cancers
X 2013 - XII 2015
2 Testing and characterization of FGF2 and FGF2-conjugates suitable for targeted therapy of FGFR-related cancers in cellular model - cell line in vitro study
X 2013 - IX 2016
3 In vivo studies in mouse xenograft models for human cancer and validation of proposed therapy
III 2015 - IX 2016

Research progress


So far, we have constructed, produced, purified and thoroughly characterized FGF2 and its variants specifically designed for chemical conjugation with cytotoxic drug.
We have also successfully conjugated FGF2 using hydrolysable peptide linker, to ensure better pharmacokinetic characteristic of the conjugate.
Biophysical analysis of obtained conjugates allowed us to confirm their native state and suitability for in vitro cellular tests.
As a cellular in vitro testing system three different groups of cell-lines are used: non-cancer cell lines naturally expressing low levels of FGFRs, cells with ectopic overexpression of FGFRs and established cell lines which overexpress FGFRs.
Using various cell lines we have confirmed cytotoxic activity of FGF2 conjugates. Different biological activity was observed depending on tested cell line and number of drug molecules attached to FGF2.
We have prepared FGF2 conjugates suitable for in vivo experiments. Mouse xenograft models for human cancer were established.

Project partners

 

ouh

Antoni Więdłocha Group
Department of Biochemistry
Institute for Cancer Research        
The Norwegian Radium Hospital
Oslo University Hospital
Montebello, 0310 Oslo, Norway


Skjalg Bruheim
Department of Tumor Biology
Institute for Cancer Research
The Norwegian Radium Hospital
Oslo University Hospital
Montebello, 0310 Oslo, Norway


Research team

Jacek Otlewski (PhD), Principal Investigator
University of Wroclaw, Faculty of Biotechnology

Antoni Wiedlocha (PhD), project partner
Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital

Skjalg Bruheim (PhD), project partner
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital

 

Malgorzata Zakrzewska (PhD)

Daniel Krowarsch (PhD)

Piotr Jakimowicz (PhD)

Michał Kostaś (PhD)

Ellen Margrethe Haugsten (PhD)

Karolina Świderska (Msc)

Mateusz Krzyścik (Msc)

Justyna Tomala (Msc)

Marta Minkiewicz (Msc)

Katrzyna Czernik (Msc)

Sandra Gruszczyńska (Msc)


Administrative and financial management

Monika Nahorska (PhD), University of Wroclaw, Faculty of Biotechnology

 

Contact person

Monika Nahorska (PhD)
+48 71 375 26 08
monika@biotech.uni.wroc.pl


Meetings

Kick-Off meeting 21-23.10.2013, Wrocław, Poland
Project progress meeting 31.09-1.10.2014, Wrocław, Poland
Project progress meeting  7.09-8.09.2015,  Wrocław, Poland
Project progress meeting 10.08.-11.08.2016, Wrocław, Poland

This project is funded from Norway Grants in the Polish-Norwegian Research Programme operated by the National Centre for Research and Development

 



PNlogo       pnrf      ncbir


 

 

Photos

Research team, Department of Protein Engineering, University of Wrocław 

 

Project progress meeting  7.09-8.09.2015,  Wrocław, Poland 

 


 

 
 
 
 
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