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Open AccessArticle

Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

1
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14A, 50-383 Wroclaw, Poland
2
Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(9), 2470; https://doi.org/10.3390/ijms19092470
Received: 23 May 2018 / Revised: 17 August 2018 / Accepted: 17 August 2018 / Published: 21 August 2018
(This article belongs to the Special Issue Tumor Targeting Therapy and Selective Killing 2018)
Fibroblast growth factor 1 (FGF1) and its receptors (FGFRs) regulate crucial biological processes such as cell proliferation and differentiation. Aberrant activation of FGFRs by their ligands can promote tumor growth and angiogenesis in many tumor types, including lung or breast cancer. The development of FGF1-targeting molecules with potential implications for the therapy of FGF1-driven tumors is recently being considered a promising approach in the treatment of cancer. In this study we have used phage display selection to find scFv antibody fragments selectively binding FGF1 and preventing it from binding to its receptor. Three identified scFv clones were expressed and characterized with regard to their binding to FGF1 and ability to interfere with FGF1-induced signaling cascades activation. In the next step the scFvs were cloned to scFv-Fc format, as dimeric Fc fusions prove beneficial in prospective therapeutic application. As expected, scFvs-Fc exhibited significantly increased affinity towards FGF1. We observed strong antiproliferative activity of the scFvs and scFvs-Fc in the in vitro cell models. Presented antibody fragments serve as novel FGF1 inhibitors and can be further utilized as powerful tools to use in the studies on the selective cancer therapy. View Full-Text
Keywords: scFv antibody fragments; scFv-Fc fusions; phage display; FGF1; FGFR; ligand trap; tumor targeting treatment; growth factor receptor targeting scFv antibody fragments; scFv-Fc fusions; phage display; FGF1; FGFR; ligand trap; tumor targeting treatment; growth factor receptor targeting
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Chudzian, J.; Szlachcic, A.; Zakrzewska, M.; Czub, M.; Pustula, M.; Holak, T.A.; Otlewski, J. Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity. Int. J. Mol. Sci. 2018, 19, 2470.

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