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Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity.
Int J Mol Sci 2018; 19(9)IJ

Abstract

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.

Authors+Show Affiliations

Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14A, 50-383 Wroclaw, Poland. julia.chudzian@uwr.edu.pl.Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14A, 50-383 Wroclaw, Poland. anna.szlachcic@uwr.edu.pl.Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14A, 50-383 Wroclaw, Poland. malgorzata.zakrzewska@uwr.edu.pl.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. miroslawa.luty@gmail.com.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. pustula.marcin@gmail.com.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. holak@chemia.uj.edu.pl.Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14A, 50-383 Wroclaw, Poland. jacek.otlewski@uwr.edu.pl.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30134556

Citation

Chudzian, Julia, et al. "Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity." International Journal of Molecular Sciences, vol. 19, no. 9, 2018.
Chudzian J, Szlachcic A, Zakrzewska M, et al. Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity. Int J Mol Sci. 2018;19(9).
Chudzian, J., Szlachcic, A., Zakrzewska, M., Czub, M., Pustula, M., Holak, T. A., & Otlewski, J. (2018). Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity. International Journal of Molecular Sciences, 19(9), doi:10.3390/ijms19092470.
Chudzian J, et al. Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity. Int J Mol Sci. 2018 Aug 21;19(9) PubMed PMID: 30134556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity. AU - Chudzian,Julia, AU - Szlachcic,Anna, AU - Zakrzewska,Malgorzata, AU - Czub,Miroslawa, AU - Pustula,Marcin, AU - Holak,Tad A, AU - Otlewski,Jacek, Y1 - 2018/08/21/ PY - 2018/05/23/received PY - 2018/08/17/revised PY - 2018/08/17/accepted PY - 2018/8/24/entrez PY - 2018/8/24/pubmed PY - 2018/12/12/medline KW - FGF1 KW - FGFR KW - growth factor receptor targeting KW - ligand trap KW - phage display KW - scFv antibody fragments KW - scFv-Fc fusions KW - tumor targeting treatment JF - International journal of molecular sciences JO - Int J Mol Sci VL - 19 IS - 9 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/30134556/Specific_Antibody_Fragment_Ligand_Traps_Blocking_FGF1_Activity L2 - http://www.mdpi.com/resolver?pii=ijms19092470 DB - PRIME DP - Unbound Medicine ER -