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Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders

Anti-idiotypic binders which specifically recognize the variable region of monoclonal antibodies have proven to be robust tools for pharmacokinetic studies of antibody therapeutics and for the development of cancer vaccines. In the present investigation, we focused on the identification of anti-idio...

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Autores principales: Könning, Doreen, Rhiel, Laura, Empting, Martin, Grzeschik, Julius, Sellmann, Carolin, Schröter, Christian, Zielonka, Stefan, Dickgießer, Stephan, Pirzer, Thomas, Yanakieva, Desislava, Becker, Stefan, Kolmar, Harald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575089/
https://www.ncbi.nlm.nih.gov/pubmed/28852148
http://dx.doi.org/10.1038/s41598-017-10513-9
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author Könning, Doreen
Rhiel, Laura
Empting, Martin
Grzeschik, Julius
Sellmann, Carolin
Schröter, Christian
Zielonka, Stefan
Dickgießer, Stephan
Pirzer, Thomas
Yanakieva, Desislava
Becker, Stefan
Kolmar, Harald
author_facet Könning, Doreen
Rhiel, Laura
Empting, Martin
Grzeschik, Julius
Sellmann, Carolin
Schröter, Christian
Zielonka, Stefan
Dickgießer, Stephan
Pirzer, Thomas
Yanakieva, Desislava
Becker, Stefan
Kolmar, Harald
author_sort Könning, Doreen
collection PubMed
description Anti-idiotypic binders which specifically recognize the variable region of monoclonal antibodies have proven to be robust tools for pharmacokinetic studies of antibody therapeutics and for the development of cancer vaccines. In the present investigation, we focused on the identification of anti-idiotypic, shark-derived IgNAR antibody variable domains (vNARs) targeting the therapeutic antibodies matuzumab and cetuximab for the purpose of developing specific capturing ligands. Using yeast surface display and semi-synthetic, CDR3-randomized libraries, we identified several highly specific binders targeting both therapeutic antibodies in their corresponding variable region, without applying any counter selections during screening. Importantly, anti-idiotypic vNAR binders were not cross-reactive towards cetuximab or matuzumab, respectively, and comprised good target recognition in the presence of human and mouse serum. When coupled to magnetic beads, anti-idiotypic vNAR variants could be used as efficient capturing tools. Moreover, a two-step procedure involving vNAR-functionalized beads was employed for the enrichment of potentially bispecific cetuximab × matuzumab antibody constructs. In conclusion, semi-synthetic and CDR3-randomized vNAR libraries in combination with yeast display enable the fast and facile identification of anti-idiotypic vNAR domains targeting monoclonal antibodies primarily in an anti-idiotypic manner.
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spelling pubmed-55750892017-09-01 Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders Könning, Doreen Rhiel, Laura Empting, Martin Grzeschik, Julius Sellmann, Carolin Schröter, Christian Zielonka, Stefan Dickgießer, Stephan Pirzer, Thomas Yanakieva, Desislava Becker, Stefan Kolmar, Harald Sci Rep Article Anti-idiotypic binders which specifically recognize the variable region of monoclonal antibodies have proven to be robust tools for pharmacokinetic studies of antibody therapeutics and for the development of cancer vaccines. In the present investigation, we focused on the identification of anti-idiotypic, shark-derived IgNAR antibody variable domains (vNARs) targeting the therapeutic antibodies matuzumab and cetuximab for the purpose of developing specific capturing ligands. Using yeast surface display and semi-synthetic, CDR3-randomized libraries, we identified several highly specific binders targeting both therapeutic antibodies in their corresponding variable region, without applying any counter selections during screening. Importantly, anti-idiotypic vNAR binders were not cross-reactive towards cetuximab or matuzumab, respectively, and comprised good target recognition in the presence of human and mouse serum. When coupled to magnetic beads, anti-idiotypic vNAR variants could be used as efficient capturing tools. Moreover, a two-step procedure involving vNAR-functionalized beads was employed for the enrichment of potentially bispecific cetuximab × matuzumab antibody constructs. In conclusion, semi-synthetic and CDR3-randomized vNAR libraries in combination with yeast display enable the fast and facile identification of anti-idiotypic vNAR domains targeting monoclonal antibodies primarily in an anti-idiotypic manner. Nature Publishing Group UK 2017-08-29 /pmc/articles/PMC5575089/ /pubmed/28852148 http://dx.doi.org/10.1038/s41598-017-10513-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Könning, Doreen
Rhiel, Laura
Empting, Martin
Grzeschik, Julius
Sellmann, Carolin
Schröter, Christian
Zielonka, Stefan
Dickgießer, Stephan
Pirzer, Thomas
Yanakieva, Desislava
Becker, Stefan
Kolmar, Harald
Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
title Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
title_full Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
title_fullStr Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
title_full_unstemmed Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
title_short Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
title_sort semi-synthetic vnar libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575089/
https://www.ncbi.nlm.nih.gov/pubmed/28852148
http://dx.doi.org/10.1038/s41598-017-10513-9
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