2. Academic Validation
  3. Fibroblast Growth Factor 2 Conjugated with Monomethyl Auristatin E Inhibits Tumor Growth in a Mouse Model

Fibroblast Growth Factor 2 Conjugated with Monomethyl Auristatin E Inhibits Tumor Growth in a Mouse Model

  • Biomacromolecules. 2021 Oct 11;22(10):4169-4180. doi: 10.1021/acs.biomac.1c00662.
Mateusz A Krzyscik 1,  Malgorzata Zakrzewska 1,  Vigdis Sørensen 2 3,  Geir Frode Øy 4,  Skjalg Brunheim 4,  Ellen M Haugsten 3 4,  Gunhild M Mælandsmo 4 5,  Antoni Wiedlocha 3 6 7,  Jacek Otlewski 1
Affiliations

Affiliations

  • 1 Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, Wroclaw 50-383, Poland.
  • 2 Advanced Light Microscopy Core Facility, Dept. Core Facilities, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo 0379, Norway.
  • 3 Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Montebello, Oslo 0379, Norway.
  • 4 Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo 0379, Norway.
  • 5 University in Tromso - Arctic University of Norway, Tromso 9019, Norway.
  • 6 Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo 0379, Norway.
  • 7 Military Institute of Hygiene and Epidemiology, Warsaw 01-163, Poland.
PMID: 34542998 DOI: 10.1021/acs.biomac.1c00662
Abstract

Worldwide, Cancer is the second leading cause of death. Regardless of the continuous progress in medicine, we still do not have a fully effective anti-cancer therapy. Therefore, the search for new targeted anti-cancer drugs is still an unmet need. Here, we present novel protein-drug conjugates that inhibit tumor growth in a mouse model of human breast Cancer. We developed conjugates based on Fibroblast Growth Factor (FGF2) with improved biophysical and biological properties for the efficient killing of Cancer cells overproducing Fibroblast Growth Factor receptor 1 (FGFR1). We used hydrophilic and biocompatible PEG4 or PEG27 molecules as a spacer between FGF2 and the toxic agent monomethyl Auristatin E. All conjugates exhibited a cytotoxic effect on FGFR1-positive Cancer cell lines. The conjugate with the highest hydrodynamic size (42 kDa) and cytotoxicity was found to efficiently inhibit tumor growth in a mouse model of human breast Cancer.

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