Evidence map›Paper›PMID 25517312›Full record

ArticlemAbs2014

A general approach to antibody thermostabilization.

Audrey D McConnell, Xue Zhang, John L Macomber, Betty Chau, Joseph C Sheffer, Sorena Rahmanian, Eric Hare, Vladimir Spasojevic, Robert A Horlick, David J King and 1 more

Abstract read
In one paragraph

Article in mAbs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

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  15. Nanobody Repertoires for Exposing Vulnerabilities of SARS-CoV-2.bioRxiv : the preprint server for biology · 2021
    Article
  16. Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. 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

11 authors.

Audrey D McConnella AnaptysBio, Inc. ; San Diego , CA USA.
Xue Zhang
John L Macomber
Betty Chau
Joseph C Sheffer
Sorena Rahmanian
Eric Hare
Vladimir Spasojevic
Robert A Horlick
David J King
Peter M Bowers

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody engineering to enhance thermostability may enable further application and ease of use of antibodies across a number of different areas. A modified human IgG framework has been developed through a combination of engineering approaches, which can be used to stabilize antibodies of diverse specificity. This is achieved through a combination of complementarity-determining region (CDR)-grafting onto the stable framework, mammalian cell display and in vitro somatic hypermutation (SHM). This approach allows both stabilization and maturation to affinities beyond those of the original antibody, as shown by the stabilization of an anti-HA33 antibody by approximately 10°C and affinity maturation of approximately 300-fold over the original antibody. Specificities of 10 antibodies of diverse origin were successfully transferred to the stable framework through CDR-grafting, with 8 of these successfully stabilized, including the therapeutic antibodies adalimumab, stabilized by 9.9°C, denosumab, stabilized by 7°C, cetuximab stabilized by 6.9°C and to a lesser extent trastuzumab stabilized by 0.8°C. This data suggests that this approach may be broadly useful for improving the biophysical characteristics of antibodies across a number of applications.

Indexed as

AdalimumabAnimalsAntibodiesAntibodies, Monoclonal, HumanizedAntibody AffinityCalorimetry, Differential ScanningCell Surface Display TechniquesCetuximabComplementarity Determining RegionsDenosumabHEK293 CellsHumansImmunoglobulin GModels, MolecularProtein ConformationProtein EngineeringAdalimumabAntibodiesAntibodies, Monoclonal, HumanizedCetuximabComplementarity Determining RegionsDenosumabImmunoglobulin GTrastuzumabaffinity maturationCDR, complementarity-determining regionCH2, heavy chain constant domain 2CH3, heavy chain constant domain 3DSC, differential scanning calorimetryHC, heavy chainLC, light chainmonoclonal antibodiesNGF, β-nerve growth factorprotein engineeringSHM, somatic hypermutationsolubilitysomatic hypermutationSPR, surface plasmon resonancethermostabilityTm, melting temperatureTNF, tumor necrosis factorVH, heavy chain variable regionVL, light chain variable region

Identifiers

PMID25517312
PMCPMC4623350

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.