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, Verlagsversion
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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 |
| Zugehörige Links: | |
| 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. |
| Status: | Verlagsversion |
| 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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- Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders. (deposited 17 Sep 2017 19:55) [Gegenwärtig angezeigt]
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