Evidence map›Paper›PMID 25484051›Full record

ArticlemAbs2015

Affinity maturation of a novel antagonistic human monoclonal antibody with a long VH CDR3 targeting the Class A GPCR formyl-peptide receptor 1.

Julie A Douthwaite, Sudharsan Sridharan, Catherine Huntington, Jayne Hammersley, Rose Marwood, Jonna K Hakulinen, Margareta Ek, Tove Sjögren, David Rider, Cyril Privezentzev and 9 more

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 39 citations in OpenAlex.

  1. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Review
  3. Article
  4. Antibody Affinity and Stability Maturation by Error-Prone PCR.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Anti-PrPAnnals of clinical and translational neurology · 2019
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

19 authors at 2 institutions in 2 countries.

Julie A Douthwaitea MedImmune Ltd. ; Cambridge , UK.
Sudharsan Sridharan
Catherine Huntington
Jayne Hammersley
Rose Marwood
Jonna K Hakulinen
Margareta Ek
Tove Sjögren
David Rider
Cyril Privezentzev
Jonathan C Seaman
Peter Cariuk
Vikki Knights
Joyce Young
Trevor Wilkinson
Matthew Sleeman
Donna K Finch
David C Lowe
Tristan J Vaughan
AstraZeneca (Sweden) · SEAstraZeneca (Singapore) · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic monoclonal antibodies targeting G-protein-coupled receptors (GPCRs) are desirable for intervention in a wide range of disease processes. The discovery of such antibodies is challenging due to a lack of stability of many GPCRs as purified proteins. We describe here the generation of Fpro0165, a human anti-formyl peptide receptor 1 (FPR1) antibody generated by variable domain engineering of an antibody derived by immunization of transgenic mice expressing human variable region genes. Antibody isolation and subsequent engineering of affinity, potency and species cross-reactivity using phage display were achieved using FPR1 expressed on HEK cells for immunization and selection, along with calcium release cellular assays for antibody screening. Fpro0165 shows full neutralization of formyl peptide-mediated activation of primary human neutrophils. A crystal structure of the Fpro0165 Fab shows a long, protruding VH CDR3 of 24 amino acids and in silico docking with a homology model of FPR1 suggests that this long VH CDR3 is critical to the predicted binding mode of the antibody. Antibody mutation studies identify the apex of the long VH CDR3 as key to mediating the species cross-reactivity profile of the antibody. This study illustrates an approach for antibody discovery and affinity engineering to typically intractable membrane proteins such as GPCRs.

Indexed as

Molecular Docking SimulationAnimalsAntibodies, MonoclonalCHO CellsComplementarity Determining RegionsCricetinaeCricetulusCrystallography, X-RayHEK293 CellsHumansImmunoglobulin Heavy ChainsMiceNeutrophilsProtein Structure, QuaternaryReceptors, Formyl PeptideAntibodies, MonoclonalComplementarity Determining RegionsFPR1 protein, humanImmunoglobulin Heavy ChainsReceptors, Formyl Peptideaffinity maturationantibody crystal structureantibody engineeringCDR, complementarity determining regionFLIPR, Fluorescent Imaging Plate ReaderFMAT, fluorometric microvolume assay technologyformyl peptide receptor-1FPR, formyl peptide receptorFv, variable domainGPCR, G-protein coupled receptorG-protein coupled receptorhomology modelingIgG, immunoglobulin Glong CDRMPL, magnetic proteoliposomephage displayRIMMS, repetitive immunization at multiple sitesscFv, single chain Fv fragmentVH, variable heavyVL, variable light

Identifiers

PMID25484051
PMCPMC4622665
OpenAlexW2046046314

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.