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Data from Antiangiogenic Activity of a Neutralizing Human Single-Chain Antibody Fragment against Fibroblast Growth Factor Receptor 1

Authors :
Patrizia Dell'Era
Marco Presta
Stefano Calza
Daniela Coltrini
Patrizia Alessi
Michela Corsini
Mirella Belleri
Chiara Urbinati
Daria Leali
Patrizia Benzoni
Roberto Ronca
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

Abstract

Fibroblast growth factor receptor-1 (FGFR-1) transduces proangiogenic and proliferative signals in human cancers. Thus, FGFR-1 may represent a target for the development of antiangiogenic/antineoplastic therapies. We screened a human single-chain fragment variable (scFv) antibody phage display library against the extracellular domain of the FGFR-1-IIIc isoform that harbors the FGF binding site. Several phages were isolated and tested for specificity and sensitivity, and the most promising antibody fragment RR-C2 was characterized for its biochemical and biological properties. ScFv RR-C2 specifically recognizes FGFR-1α and FGFR-1β isoforms in ELISA, Western blotting, and surface plasmon resonance analysis with a Kd value of 300 and 144 nmol/L for the 2 receptor isoforms, respectively. The antibody fragment also recognizes FGFR-1 when the receptor is exposed on the cell surface, thus preventing the formation of the ternary complex among FGFR-1, its ligand FGF2, and cell surface heparan sulfate proteoglycans. Accordingly, scFv RR-C2 specifically inhibits FGF2-mediated mitogenic activity in endothelial cells of human, bovine, and murine origin in a nanomolar range of concentrations. Also, the antibody fragment prevents FGF2-triggered sprouting of both human umbilical vein endothelial cell spheroids and of murine endothelium from aortic rings. Finally, the antibody fragment hampers the angiogenic activity exerted both by FGF2 in the chick embryo chorioallantoic membrane assay and by S115 mouse mammary tumor cells in the Matrigel plug assay. Taken together, the data show that scFv RR-C2 recognizes and neutralizes FGFR-1 activity in different animal species, including humans, thus representing a novel tool for the development of antiangiogenic/antineoplastic therapies. Mol Cancer Ther; 9(12); 3244–53. ©2010 AACR.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....148043a51389b9be7583a2a7b6f5214b
Full Text :
https://doi.org/10.1158/1535-7163.c.6531530