Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody

Abstract Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibod...

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Autores principales:	Rodrigo Barbosa de Aguiar, Tábata de Almeida da Silva, Bruno Andrade Costa, Marcelo Ferreira Marcondes Machado, Renata Yoshiko Yamada, Camila Braggion, Kátia Regina Perez, Marcelo Alves Silva Mori, Vitor Oliveira, Jane Zveiter de Moraes
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c479d1dc3885419f9263069f0a30f633
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spelling	oai:doaj.org-article:c479d1dc3885419f9263069f0a30f6332021-12-02T14:12:42ZGeneration and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody10.1038/s41598-020-80746-82045-2322https://doaj.org/article/c479d1dc3885419f9263069f0a30f6332021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80746-8https://doaj.org/toc/2045-2322Abstract Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibody (mAb), named 3F12E7, with notable antitumor potential revealed by preclinical assays. FGF2 is a known angiogenesis-associated molecule implicated in tumor progression. In this report, we describe a recombinant scFv format for the 3F12E7 mAb. The results demonstrate that the generated 3F12E7 scFv, although prone to aggregation, comprises an active anti-FGF2 product that contains monomers and small oligomers. Functionally, the 3F12E7 scFv preparations specifically recognize FGF2 and inhibit tumor growth similar to the corresponding full-length IgG counterpart in an experimental model. In silico molecular analysis provided insights into the aggregation propensity and the antigen-recognition by scFv units. Antigen-binding determinants were predicted outside the most aggregation-prone hotspots. Overall, our experimental and prediction dataset describes an scFv scaffold for the 3F12E7 mAb and also provides insights to further engineer non-aggregated anti-FGF2 scFv-based tools for therapeutic and research purposes.Rodrigo Barbosa de AguiarTábata de Almeida da SilvaBruno Andrade CostaMarcelo Ferreira Marcondes MachadoRenata Yoshiko YamadaCamila BraggionKátia Regina PerezMarcelo Alves Silva MoriVitor OliveiraJane Zveiter de MoraesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodrigo Barbosa de Aguiar Tábata de Almeida da Silva Bruno Andrade Costa Marcelo Ferreira Marcondes Machado Renata Yoshiko Yamada Camila Braggion Kátia Regina Perez Marcelo Alves Silva Mori Vitor Oliveira Jane Zveiter de Moraes Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody
description	Abstract Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibody (mAb), named 3F12E7, with notable antitumor potential revealed by preclinical assays. FGF2 is a known angiogenesis-associated molecule implicated in tumor progression. In this report, we describe a recombinant scFv format for the 3F12E7 mAb. The results demonstrate that the generated 3F12E7 scFv, although prone to aggregation, comprises an active anti-FGF2 product that contains monomers and small oligomers. Functionally, the 3F12E7 scFv preparations specifically recognize FGF2 and inhibit tumor growth similar to the corresponding full-length IgG counterpart in an experimental model. In silico molecular analysis provided insights into the aggregation propensity and the antigen-recognition by scFv units. Antigen-binding determinants were predicted outside the most aggregation-prone hotspots. Overall, our experimental and prediction dataset describes an scFv scaffold for the 3F12E7 mAb and also provides insights to further engineer non-aggregated anti-FGF2 scFv-based tools for therapeutic and research purposes.
format	article
author	Rodrigo Barbosa de Aguiar Tábata de Almeida da Silva Bruno Andrade Costa Marcelo Ferreira Marcondes Machado Renata Yoshiko Yamada Camila Braggion Kátia Regina Perez Marcelo Alves Silva Mori Vitor Oliveira Jane Zveiter de Moraes
author_facet	Rodrigo Barbosa de Aguiar Tábata de Almeida da Silva Bruno Andrade Costa Marcelo Ferreira Marcondes Machado Renata Yoshiko Yamada Camila Braggion Kátia Regina Perez Marcelo Alves Silva Mori Vitor Oliveira Jane Zveiter de Moraes
author_sort	Rodrigo Barbosa de Aguiar
title	Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody
title_short	Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody
title_full	Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody
title_fullStr	Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody
title_full_unstemmed	Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody
title_sort	generation and functional characterization of a single-chain variable fragment (scfv) of the anti-fgf2 3f12e7 monoclonal antibody
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c479d1dc3885419f9263069f0a30f633
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Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody

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