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ACS Omega. 2017 Jul 31;2(7):3792-3805. doi: 10.1021/acsomega.7b00116. Epub 2017 Jul 21.

Cytotoxic Conjugates of Fibroblast Growth Factor 2 (FGF2) with Monomethyl Auristatin E for Effective Killing of Cells Expressing FGF Receptors.

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Department of Protein Engineering and Department of Protein Biotechnology, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
Department of Core Facilities and Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway.


Antibody-drug conjugates (ADCs) are a new class of anticancer therapeutics that combine the selectivity of targeted treatment, ensured by monoclonal antibodies, with the potency of the cytotoxic agent. Here, we applied an analogous approach, but instead of an antibody, we used fibroblast growth factor 2 (FGF2). FGF2 is a natural ligand of fibroblast growth factor receptor 1 (FGFR1), a cell-surface receptor reported to be overexpressed in several types of tumors. We developed and characterized FGF2 conjugates containing a defined number of molecules of highly cytotoxic drug monomethyl auristatin E (MMAE). These conjugates effectively targeted FGFR1-expressing cells, were internalized upon FGFR1-mediated endocytosis, and, in consequence, revealed high cytotoxicity, which was clearly related to the FGFR1 expression level. Among the conjugates tested, the most potent was that bearing three MMAE molecules, showing that the cytotoxicity of protein-drug conjugates in vitro is directly dependent on drug loading.

Conflict of interest statement

The authors declare no competing financial interest.

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