Evidence map›Paper›PMID 28852148›Full record

ArticleScientific reports2017

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

Doreen Könning, Laura Rhiel, Martin Empting, Julius Grzeschik, Carolin Sellmann, Christian Schröter, Stefan Zielonka, Stephan Dickgießer, Thomas Pirzer, Desislava Yanakieva and 2 more

Abstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. VNAR development through antigen immunization of Japanese topeshark (Frontiers in bioengineering and biotechnology · 2023
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Single Domain Antibodies as New Biomarker Detectors.Diagnostics (Basel, Switzerland) · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Doreen KönningInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287, Darmstadt, Germany.
Laura RhielAntibody-Drug Conjugates and Targeted NBE Therapeutics, Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
Martin EmptingHelmholtz-Institut für Pharmazeutische Forschung Saarland (HIPS), Department Drug Design and Optimization (DDOP), Campus E8.1, 66123, Saarbrücken, Germany.ORCID 0000-0002-0503-5830
Julius GrzeschikInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287, Darmstadt, Germany.
Carolin SellmannProtein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
Christian SchröterAntibody-Drug Conjugates and Targeted NBE Therapeutics, Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
Stefan ZielonkaProtein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
Stephan DickgießerAntibody-Drug Conjugates and Targeted NBE Therapeutics, Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
Thomas PirzerInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287, Darmstadt, Germany.
Desislava YanakievaInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287, Darmstadt, Germany.
Stefan BeckerProtein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
Harald KolmarInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287, Darmstadt, Germany. Kolmar@Biochemie-TUD.de.ORCID 0000-0002-8210-1993

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Cell Surface Display TechniquesAntibodies, Anti-IdiotypicAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCetuximabImmunomagnetic SeparationProtein BindingSaccharomyces cerevisiaeSingle-Domain AntibodiesAntibodies, Anti-IdiotypicAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCetuximabmatuzumabSingle-Domain Antibodies

Identifiers

PMID28852148
PMCPMC5575089

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.