Evidence map›Paper›PMID 27625211›Full record

ArticlemAbs2016

Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody.

James R Apgar, Michelle Mader, Rita Agostinelli, Susan Benard, Peter Bialek, Mark Johnson, Yijie Gao, Mark Krebs, Jane Owens, Kevin Parris and 4 more

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.8field-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

26 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Myostatin: A Skeletal Muscle Chalone.Annual review of physiology · 2023
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Directed evolution methods for overcoming trade-offs between protein activity and stability.AIChE journal. American Institute of Chemical Engineers · 2020
    Article
  16. Article
  17. Structural biology of the TGFβ family.Experimental biology and medicine (Maywood, N.J.) · 2019
    Review
  18. Local and global anatomy of antibody-protein antigen recognition.Journal of molecular recognition : JMR · 2018
    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

14 authors at 1 institution in 1 country.

James R Apgara Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Michelle Madera Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Rita Agostinellia Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Susan Benarda Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Peter Bialekb Rare Disease Research Unit, Pfizer Inc. , Cambridge , MA , USA.
Mark Johnsonb Rare Disease Research Unit, Pfizer Inc. , Cambridge , MA , USA.
Yijie Gaoa Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Mark Krebsa Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Jane Owensb Rare Disease Research Unit, Pfizer Inc. , Cambridge , MA , USA.
Kevin Parrisa Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Michael St Andreb Rare Disease Research Unit, Pfizer Inc. , Cambridge , MA , USA.
Kris Svensona Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Carl Morrisb Rare Disease Research Unit, Pfizer Inc. , Cambridge , MA , USA.
Lioudmila Tchistiakovaa Biomedicine Design, Pfizer Inc. , Cambridge , MA , USA.
Pfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies. To accomplish this, we solved the co-crystal structures of myostatin with the chimeric (Protein Databank (PDB) id 5F3B) and CDR-grafted anti-myostatin antibody (PDB id 5F3H), allowing us to computationally predict the structurally important CDR residues as well as those making significant contacts with the antigen. Structure-based rational design enabled further germlining of the CDR-grafted antibody, reducing the murine content of the antibody without affecting antigen binding. The overall "humanness" was increased for both the light and heavy chain variable regions.

Indexed as

AnimalsAntibodies, MonoclonalComplementarity Determining RegionsHumansMiceModels, MolecularMyostatinProtein EngineeringAntibodies, MonoclonalComplementarity Determining RegionsMSTN protein, humanMyostatinAntibodyantibody engineeringcomplementarity-determining regionhumanizationimmunogenicityin silico designmyostatinX-ray crystallography

Identifiers

PMID27625211
PMCPMC5058614
OpenAlexW2519574571

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.