Evidence map›Paper›PMID 24830649›Full record

ArticlemAbs

Generation of a high-fidelity antibody against nerve growth factor using library scanning mutagenesis and validation with structures of the initial and optimized Fab-antigen complexes.

Sherry L La Porte, Charles Eigenbrot, Mark Ultsch, Wei-Hsien Ho, Davide Foletti, Alison Forgie, Kevin C Lindquist, David L Shelton, Jaume Pons

Open access · goldAbstract read
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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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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

9 authors at 4 institutions in 1 country.

Sherry L La Porte
Charles Eigenbrot
Mark Ultsch
Wei-Hsien Ho
Davide Foletti
Alison Forgie
Kevin C Lindquist
David L Shelton
Jaume Pons
Kaiser Permanente South San Francisco Medical Center · USPfizer (United States) · USAtotech (United States) · USJoint Center for Structural Genomics · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nerve growth factor (NGF) is indispensable during normal embryonic development and critical for the amplification of pain signals in adults. Intervention in NGF signaling holds promise for the alleviation of pain resulting from human diseases such as osteoarthritis, cancer and chronic lower back disorders. We developed a fast, high-fidelity method to convert a hybridoma-derived NGF-targeted mouse antibody into a clinical candidate. This method, termed Library Scanning Mutagenesis (LSM), resulted in the ultra-high affinity antibody tanezumab, a first-in-class anti-hyperalgesic specific for an NGF epitope. Functional and structural comparisons between tanezumab and the mouse 911 precursor antibody using neurotrophin-specific cell survival assays and X-ray crystal structures of both Fab-antigen complexes illustrated high fidelity retention of the NGF epitope. These results suggest the potential for wide applicability of the LSM method for optimization of well-characterized antibodies during humanization.

Indexed as

Antibodies, Monoclonal, Murine-DerivedAntigen-Antibody ComplexEpitopesMutagenesisNerve Growth FactorAdultAnimalsAntibodies, Monoclonal, HumanizedCells, CulturedCrystallography, X-RayFemaleHumansLow Back PainMiceNeoplasmsOsteoarthritisAntibodies, Monoclonal, HumanizedAntibodies, Monoclonal, Murine-DerivedAntigen-Antibody ComplexEpitopesNerve Growth FactorNGF protein, humanSingle-Chain Antibodiestanezumab

Identifiers

PMID24830649
PMCPMC4171009
OpenAlexW2090058067

What OpenQuestion holds

Textmetadata
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.