Evidence map›Paper›PMID 30997002›Full record

ArticleChemical science2019

Hybrid mass spectrometry methods reveal lot-to-lot differences and delineate the effects of glycosylation on the tertiary structure of Herceptin®.

Rosie Upton, Lukasz G Migas, Kamila J Pacholarz, Richard G Beniston, Sian Estdale, David Firth, Perdita E Barran

Open access · diamondAbstract read
In one paragraph

Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 33 citations in OpenAlex.

  1. Hybrid Mass Spectrometry Applied across the Production of Antibody Biotherapeutics.Journal of the American Society for Mass Spectrometry · 2025
    Article
  2. Impact ofBiochemistry · 2024
    Article
  3. Expanding Native Mass Spectrometry to the Masses.Journal of the American Society for Mass Spectrometry · 2024
    Article
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  14. Glycoproteomics Technologies in Glycobiotechnology.Advances in biochemical engineering/biotechnology · 2021
    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

7 authors at 2 institutions in 4 countries.

Rosie UptonManchester Institute of Biotechnology , Michael Barber Centre for Collaborative Mass Spectrometry , University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK . Email: Perdita.barran@manchester.ac.uk.ORCID 0000-0001-7204-2910
Lukasz G MigasManchester Institute of Biotechnology , Michael Barber Centre for Collaborative Mass Spectrometry , University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK . Email: Perdita.barran@manchester.ac.uk.ORCID 0000-0002-1884-6405
Kamila J PacholarzManchester Institute of Biotechnology , Michael Barber Centre for Collaborative Mass Spectrometry , University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK . Email: Perdita.barran@manchester.ac.uk.ORCID 0000-0003-2712-7557
Richard G BenistonCovance Laboratories Ltd. , Otley Road , Harrogate , HG3 1PY , UK.
Sian EstdaleCovance Laboratories Ltd. , Otley Road , Harrogate , HG3 1PY , UK.ORCID 0000-0003-4374-5320
David FirthCovance Laboratories Ltd. , Otley Road , Harrogate , HG3 1PY , UK.ORCID 0000-0003-3558-2955
Perdita E BarranManchester Institute of Biotechnology , Michael Barber Centre for Collaborative Mass Spectrometry , University of Manchester , 131 Princess Street , Manchester , M1 7DN , UK . Email: Perdita.barran@manchester.ac.uk.ORCID 0000-0002-7720-586X
University of Manchester · GBHarrogate District Hospital · GB

Funding

Biotechnology and Biological Sciences Research Council BB/H013636/1Biotechnology and Biological Sciences Research Council BB/K017802/1Biotechnology and Biological Sciences Research Council BB/M017702/1
6 · The paper itself

Abstract

To quantify the measurable variations in the structure of a biopharmaceutical product we systematically evaluate three lots of Herceptin®, two mAb standards and an intact Fc-hinge fragment. Each mAb is examined in three states; glycan intact, truncated (following endoS2 treatment) and fully deglycosylated. Despite equivalence at the intact protein level, each lot of Herceptin® gives a distinctive signature in three different mass spectrometry approaches. Ion mobility mass spectrometry (IM-MS) shows that in the API, the attached N-glycans reduce the conformational spread of each mAb by 10.5-25%. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) data support this, with lower global deuterium uptake in solution when comparing intact to the fully deglycosylated protein. HDX-MS and activated IM-MS map the influence of glycans on the mAb and reveal allosteric effects which extend far beyond the Fc domains into the Fab region. Taken together, these findings and the supplied interactive data sets establish acceptance criteria with application for MS based characterisation of biosimilars and novel therapeutic mAbs.

Identifiers

PMID30997002
PMCPMC6425993
OpenAlexW2909702570

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.