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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)
Artikel, Zweitveröffentlichung

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Kurzbeschreibung (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.

Typ des Eintrags: Artikel
Erschienen: 2017
Autor(en): Könning, Doreen ; Rhiel, Laura ; Empting, Martin ; Grzeschik, Julius ; Sellmann, Carolin ; Schröter, Christian ; Zielonka, Stefan ; Dickgießer, Stephan ; Pirzer, Thomas ; Yanakieva, Desislava ; Becker, Stefan ; Kolmar, Harald
Art des Eintrags: Zweitveröffentlichung
Titel: Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders
Sprache: Englisch
Publikationsjahr: 2017
Ort: Darmstadt
Publikationsdatum der Erstveröffentlichung: 2017
Verlag: Springer Nature
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Scientific Reports
Jahrgang/Volume einer Zeitschrift: 7
(Heft-)Nummer: 1
URL / URN: http://tuprints.ulb.tu-darmstadt.de/6795
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Herkunft: Zweitveröffentlichung aus gefördertem Golden Open Access
Kurzbeschreibung (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
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 540 Chemie
Fachbereich(e)/-gebiet(e): 07 Fachbereich Chemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie > Allgemeine Biochemie
Hinterlegungsdatum: 17 Sep 2017 19:55
Letzte Änderung: 05 Jan 2024 10:07
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