Evidence map›Paper›PMID 30339473›Full record

ArticlemAbs

Evidence of disulfide bond scrambling during production of an antibody-drug conjugate.

Lily Pei-Yao Liu-Shin, Adam Fung, Arun Malhotra, Gayathri Ratnaswamy

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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Site-SpecificBioconjugate chemistry · 2023
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. 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

4 authors at 1 institution in 1 country.

Lily Pei-Yao Liu-Shina Analytical and Formulation Development , Agensys, Inc., an affiliate of Astellas, Inc , Santa Monica , CA , USA.ORCID 0000-0001-8156-1739
Adam Funga Analytical and Formulation Development , Agensys, Inc., an affiliate of Astellas, Inc , Santa Monica , CA , USA.ORCID 0000-0002-7911-817X
Arun Malhotrab Department of Biochemistry and Molecular Biology , University of Miami Miller School of Medicine , Miami , FL , USA.ORCID 0000-0001-6656-7841
Gayathri Ratnaswamya Analytical and Formulation Development , Agensys, Inc., an affiliate of Astellas, Inc , Santa Monica , CA , USA.ORCID 0000-0001-9377-1696
University of Miami · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) that are formed using thiol-maleimide chemistry are commonly produced by reactions that occur at or above neutral pHs. Alkaline environments can promote disulfide bond scrambling, and may result in the reconfiguration of interchain disulfide bonds in IgG antibodies, particularly in the IgG2 and IgG4 subclasses. IgG2-A and IgG2-B antibodies generated under basic conditions yielded ADCs with comparable average drug-to-antibody ratios and conjugate distributions. In contrast, the antibody disulfide configuration affected the distribution of ADCs generated under acidic conditions. The similarities of the ADCs derived from alkaline reactions were attributed to the scrambling of interchain disulfide bonds during the partial reduction step, where conversion of the IgG2-A isoform to the IgG2-B isoform was favored.

Indexed as

Antibodies, MonoclonalDisulfidesDrug CompoundingHumansHydrogen-Ion ConcentrationImmunoconjugatesImmunoglobulin GMaleimidesProtein IsoformsAntibodies, MonoclonalDisulfidesImmunoconjugatesImmunoglobulin GmaleimideMaleimidesProtein IsoformsADCantibody-drug conjugateconjugation processconjugation profiledisulfide isoformdisulfide scramblingIgG2mAbmonoclonal antibody

Identifiers

PMID30339473
PMCPMC6284598
OpenAlexW2897973518

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.