Evidence map›Paper›PMID 27981887›Full record

ArticlemAbs

Insertion of scFv into the hinge domain of full-length IgG1 monoclonal antibody results in tetravalent bispecific molecule with robust properties.

Binyam Bezabeh, Ryan Fleming, Christine Fazenbaker, Haihong Zhong, Karen Coffman, Xiang-Qing Yu, Ching Ching Leow, Nerea Gibson, Susan Wilson, C Kendall Stover and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Engineering therapeutic antibodies to combat infectious diseases.Current opinion in chemical engineering · 2018
    Article
  11. Article
  12. Article
  13. Article
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

13 authors.

Binyam Bezabeha Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.
Ryan Fleminga Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.
Christine Fazenbakerb Oncology Research , Gaithersburg , MA , USA.
Haihong Zhongb Oncology Research , Gaithersburg , MA , USA.
Karen Coffmanc Clinical Pharmacology and DMPK , Gaithersburg , MA , USA.
Xiang-Qing Yuc Clinical Pharmacology and DMPK , Gaithersburg , MA , USA.
Ching Ching Leowc Clinical Pharmacology and DMPK , Gaithersburg , MA , USA.
Nerea Gibsona Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.
Susan Wilsona Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.
C Kendall Stoverd Infectious Diseases, MedImmune , Gaithersburg , MA , USA.
Herren Wua Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.
Changshou Gaoa Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.
Nazzareno Dimasia Antibody Discovery and Protein Engineering , Gaithersburg , MA , USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

By simultaneous binding two disease mediators, bispecific antibodies offer the opportunity to broaden the utility of antibody-based therapies. Herein, we describe the design and characterization of Bs4Ab, an innovative and generic bispecific tetravalent antibody platform. The Bs4Ab format comprises a full-length IgG1 monoclonal antibody with a scFv inserted into the hinge domain. The Bs4Ab design demonstrates robust manufacturability as evidenced by MEDI3902, which is currently in clinical development. To further demonstrate the applicability of the Bs4Ab technology, we describe the molecular engineering, biochemical, biophysical, and in vivo characterization of a bispecific tetravalent Bs4Ab that, by simultaneously binding vascular endothelial growth factor and angiopoietin-2, inhibits their function. We also demonstrate that the Bs4Ab platform allows Fc-engineering similar to that achieved with IgG1 antibodies, such as mutations to extend half-life or modulate effector functions.

Indexed as

Angiopoietin-2AnimalsAntibodies, BispecificAntibodies, MonoclonalAntineoplastic AgentsColorectal NeoplasmsHumansImmunoglobulin GMiceProtein EngineeringSingle-Chain AntibodiesVascular Endothelial Growth Factor AXenograft Model Antitumor AssaysAngiopoietin-2ANGPT2 protein, humanAntibodies, BispecificAntibodies, MonoclonalAntineoplastic AgentsImmunoglobulin GSingle-Chain AntibodiesVascular Endothelial Growth Factor AVEGFA protein, humanAntibody engineeringbispecific antibodyconcurrent binding to antigensmultispecific antibodysingle-chain antibody Fvtetravalent antibody

Identifiers

PMID27981887
PMCPMC5297521

What OpenQuestion holds

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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.