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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621123
Title:
Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders.
Authors:
Könning, Doreen; Rhiel, Laura; Empting, Martin ( 0000-0002-0503-5830 ) ; Grzeschik, Julius; Sellmann, Carolin; Schröter, Christian; Zielonka, Stefan; Dickgießer, Stephan; Pirzer, Thomas; Yanakieva, Desislava; Becker, Stefan; Kolmar, Harald ( 0000-0002-8210-1993 )
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.
Affiliation:
Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
Citation:
Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders. 2017, 7 (1):9676 Sci Rep
Journal:
Scientific reports
Issue Date:
29-Aug-2017
URI:
http://hdl.handle.net/10033/621123
DOI:
10.1038/s41598-017-10513-9
PubMed ID:
28852148
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorKönning, Doreenen
dc.contributor.authorRhiel, Lauraen
dc.contributor.authorEmpting, Martinen
dc.contributor.authorGrzeschik, Juliusen
dc.contributor.authorSellmann, Carolinen
dc.contributor.authorSchröter, Christianen
dc.contributor.authorZielonka, Stefanen
dc.contributor.authorDickgießer, Stephanen
dc.contributor.authorPirzer, Thomasen
dc.contributor.authorYanakieva, Desislavaen
dc.contributor.authorBecker, Stefanen
dc.contributor.authorKolmar, Haralden
dc.date.accessioned2017-09-26T13:22:25Z-
dc.date.available2017-09-26T13:22:25Z-
dc.date.issued2017-08-29-
dc.identifier.citationSemi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders. 2017, 7 (1):9676 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid28852148-
dc.identifier.doi10.1038/s41598-017-10513-9-
dc.identifier.urihttp://hdl.handle.net/10033/621123-
dc.description.abstractAnti-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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleSemi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalScientific reportsen

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