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

Könning, Doreen and Rhiel, Laura and Empting, Martin and Grzeschik, Julius and Sellmann, Carolin and Schröter, Christian and Zielonka, Stefan and Dickgießer, Stephan and Pirzer, Thomas and Yanakieva, Desislava and Becker, Stefan and Kolmar, Harald (2017):
Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders.
In: Scientific Reports, Springer Nature, 7, (1), ISSN 2045-2322,
DOI: 10.1038/s41598-017-10513-9,
[Online-Edition: http://tuprints.ulb.tu-darmstadt.de/6795],
[Article]

Abstract

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.

Item Type: Article
Erschienen: 2017
Creators: Könning, Doreen and Rhiel, Laura and Empting, Martin and Grzeschik, Julius and Sellmann, Carolin and Schröter, Christian and Zielonka, Stefan and Dickgießer, Stephan and Pirzer, Thomas and Yanakieva, Desislava and Becker, Stefan and Kolmar, Harald
Title: Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
Language: English
Abstract:

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.

Journal or Publication Title: Scientific Reports
Volume: 7
Number: 1
Publisher: Springer Nature
Divisions: 07 Department of Chemistry > Fachgebiet Biochemie > Allgemeine Biochemie
07 Department of Chemistry > Fachgebiet Biochemie
07 Department of Chemistry
Date Deposited: 17 Sep 2017 19:55
DOI: 10.1038/s41598-017-10513-9
Official URL: http://tuprints.ulb.tu-darmstadt.de/6795
URN: urn:nbn:de:tuda-tuprints-67959
Identification Number: doi:10.1038/s41598-017-10513-9
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