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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 (2017)
Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders.
In: Scientific Reports, 2017, 7 (1)
Article, Secondary publication

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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 ; Rhiel, Laura ; Empting, Martin ; Grzeschik, Julius ; Sellmann, Carolin ; Schröter, Christian ; Zielonka, Stefan ; Dickgießer, Stephan ; Pirzer, Thomas ; Yanakieva, Desislava ; Becker, Stefan ; Kolmar, Harald
Type of entry: Secondary publication
Title: Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
Language: English
Date: 2017
Place of Publication: Darmstadt
Year of primary publication: 2017
Publisher: Springer Nature
Journal or Publication Title: Scientific Reports
Volume of the journal: 7
Issue Number: 1
URL / URN: http://tuprints.ulb.tu-darmstadt.de/6795
Corresponding Links:
Origin: Secondary publication via sponsored Golden Open Access
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.

URN: urn:nbn:de:tuda-tuprints-67959
Classification DDC: 500 Science and mathematics > 540 Chemistry
Divisions: 07 Department of Chemistry
07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie > Allgemeine Biochemie
Date Deposited: 17 Sep 2017 19:55
Last Modified: 05 Jan 2024 10:07
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