Evidence map›Paper›PMID 26728464›Full record

ArticleThe Journal of biological chemistry2016

Novel Interaction Mechanism of a Domain Antibody-based Inhibitor of Human Vascular Endothelial Growth Factor with Greater Potency than Ranibizumab and Bevacizumab and Improved Capacity over Aflibercept.

Adam Walker, Chun-Wa Chung, Margarete Neu, Manish Burman, Thil Batuwangala, Gavin Jones, Chi-Man Tang, Michael Steward, Michael Mullin, Nadia Tournier and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  11. Single ocular injection of a sustained-release anti-VEGF delivers 6months pharmacokinetics and efficacy in a primate laser CNV model.Journal of controlled release : official journal of the Controlled Release Society · 2016
    Article
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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

14 authors at 2 institutions in 1 country.

Adam WalkerFrom BioPharm Innovation.
Chun-Wa ChungMolecular Discovery Research.
Margarete NeuMolecular Discovery Research.
Manish BurmanFrom BioPharm Innovation.
Thil BatuwangalaFrom BioPharm Innovation.
Gavin JonesFrom BioPharm Innovation.
Chi-Man TangFrom BioPharm Innovation.
Michael StewardFrom BioPharm Innovation.
Michael MullinBioPharm Discovery, and.
Nadia TournierBioPharm Discovery, and.
Alan LewisBioPharm Discovery, and.
Justyna KorczynskaFrom BioPharm Innovation,; BioPharm Discovery, and.
Vicky ChungBioPharm Process Research, GSK Medicine's Research Centre, Stevenage, Herts SG1 2NY, United Kingdom.
Ian CatchpoleFrom BioPharm Innovation,. Electronic address: ian.r.catchpole@gsk.com.
BioPharm (United Kingdom) · GBStevenage Bioscience Catalyst · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A potent VEGF inhibitor with novel antibody architecture and antigen binding mode has been developed. The molecule, hereafter referred to as VEGF dual dAb (domain antibody), was evaluated in vitro for binding to VEGF and for potency in VEGF-driven models and compared with other anti-VEGF biologics that have been used in ocular anti-angiogenic therapeutic regimes. VEGF dual dAb is more potent than bevacizumab and ranibizumab for VEGF binding, inhibition of VEGF receptor binding assays (RBAs), and VEGF-driven in vitro models of angiogenesis and displays comparable inhibition to aflibercept (Eylea). VEGF dual dAb is dimeric, and each monomer contains two distinct anti-VEGF domain antibodies attached via linkers to a human IgG1 Fc domain. Mechanistically, the enhanced in vitro potency of VEGF dual dAb, in comparison to other anti-VEGF biologics, can be explained by increased binding stoichiometry. A consistent model of the target engagement has been built based on the x-ray complexes of each of the two isolated domain antibodies with the VEGF antigen.

Indexed as

Angiogenesis InhibitorsAnimalsBevacizumabCrystallography, X-RayDrug DiscoveryHEK293 CellsHumansModels, MolecularRanibizumabReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsSingle-Domain AntibodiesSwineVascular Endothelial Growth Factor AafliberceptAngiogenesis InhibitorsBevacizumabRanibizumabReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsSingle-Domain AntibodiesVascular Endothelial Growth Factor Aangiogenesisantibody engineeringdrug actionprotein-protein interactionretinal degenerationsingle-domain antibody (sdAb, nanobody)vascular endothelial growth factor (VEGF)

Identifiers

PMID26728464
PMCPMC4786692
OpenAlexW2233530828

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.