Evidence map›Paper›PMID 26252731›Full record

ArticlemAbs2015

Antibody humanization by structure-based computational protein design.

Yoonjoo Choi, Casey Hua, Charles L Sentman, Margaret E Ackerman, Chris Bailey-Kellogg

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 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. How can we discover developable antibody-based biotherapeutics?Frontiers in molecular biosciences · 2023
    Review
  15. Analytical Method for Experimental Validation of Computer-Designed Antibody.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  16. Article
  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

5 authors at 2 institutions in 2 countries.

Yoonjoo Choia Department of Computer Science ; Dartmouth College ; Hanover , NH USA.
Casey Huab Thayer School of Engineering; Dartmouth College ; Hanover , NH USA.
Charles L Sentmanc Department of Microbiology and Immunology ; Geisel School of Medicine; Dartmouth College ; Lebanon , NH USA.
Margaret E Ackermanb Thayer School of Engineering; Dartmouth College ; Hanover , NH USA.
Chris Bailey-Kellogga Department of Computer Science ; Dartmouth College ; Hanover , NH USA.
Dartmouth College · USDartmouth Hospital · GB

Funding

Functional Deimmunization of Therapeutic ProteinsR01GM098977 · NIGMS · DARTMOUTH COLLEGE · PI BAILEY-KELLOGG, CHRIS, GRISWOLD, KARL E · 2011 to 2019
$3.4M
NIGMS NIH HHS 5P30GM10345NIGMS NIH HHS R01 GM098977NIGMS NIH HHS R01-GM-098977
6 · The paper itself

Abstract

Antibodies derived from non-human sources must be modified for therapeutic use so as to mitigate undesirable immune responses. While complementarity-determining region (CDR) grafting-based humanization techniques have been successfully applied in many cases, it remains challenging to maintain the desired stability and antigen binding affinity upon grafting. We developed an alternative humanization approach called CoDAH ("Computationally-Driven Antibody Humanization") in which computational protein design methods directly select sets of amino acids to incorporate from human germline sequences to increase humanness while maintaining structural stability. Retrospective studies show that CoDAH is able to identify variants deemed beneficial according to both humanness and structural stability criteria, even for targets lacking crystal structures. Prospective application to TZ47, a murine anti-human B7H6 antibody, demonstrates the approach. Four diverse humanized variants were designed, and all possible unique VH/VL combinations were produced as full-length IgG1 antibodies. Soluble and cell surface expressed antigen binding assays showed that 75% (6 of 8) of the computationally designed VH/VL variants were successfully expressed and competed with the murine TZ47 for binding to B7H6 antigen. Furthermore, 4 of the 6 bound with an estimated KD within an order of magnitude of the original TZ47 antibody. In contrast, a traditional CDR-grafted variant could not be expressed. These results suggest that the computational protein design approach described here can be used to efficiently generate functional humanized antibodies and provide humanized templates for further affinity maturation.

Indexed as

Drug DesignAnimalsAntibodies, Monoclonal, HumanizedComplementarity Determining RegionsComputational BiologyHumansImmunoglobulin GImmunoglobulin Variable RegionMiceModels, MolecularProspective StudiesProtein ConformationProtein EngineeringRetrospective StudiesAntibodies, Monoclonal, HumanizedComplementarity Determining RegionsImmunoglobulin GImmunoglobulin Variable Regionantibodycomputational protein designhumanizationhuman string contentpareto optimizationprotein structure analysis

Identifiers

PMID26252731
PMCPMC5045135
OpenAlexW2117246959

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.