Evidence map›Paper›PMID 28281873›Full record

ArticlemAbs

Resolving the micro-heterogeneity and structural integrity of monoclonal antibodies by hybrid mass spectrometric approaches.

Yang Yang, Guanbo Wang, Ting Song, Carlito B Lebrilla, Albert J R Heck

Abstract 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 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

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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

25 citing papers in PubMed.

  1. Review
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  7. Towards structure-focused glycoproteomics.Biochemical Society transactions · 2021
    Review
  8. Review
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  12. Review
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  18. Quantitative collision-induced unfolding differentiates model antibody-drug conjugates.Protein science : a publication of the Protein Society · 2019
    Article
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  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

5 authors.

Yang Yanga Biomolecular Mass Spectrometry and Proteomics , Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht , Utrecht , The Netherlands.
Guanbo Wanga Biomolecular Mass Spectrometry and Proteomics , Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht , Utrecht , The Netherlands.
Ting Songc Department of Chemistry , University of California , Davis , CA , USA.
Carlito B Lebrillac Department of Chemistry , University of California , Davis , CA , USA.
Albert J R Hecka Biomolecular Mass Spectrometry and Proteomics , Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht , Utrecht , The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

For therapeutic monoclonal antibodies (mAbs), detailed analysis of the structural integrity and heterogeneity, which results from multiple types of post-translational modifications (PTMs), is relevant to various processes, including product characterization, storage stability and quality control. Despite the recent rapid development of new bioanalytical techniques, it is still challenging to completely characterize the proteoform profile of a mAb. As a nearly indispensable tool in mAb analysis, mass spectrometry (MS) provides unique structural information at multiple levels. Here, we tested a hybrid strategy for the comprehensive characterization of micro-heterogeneity by integrating 2 state-of-the-art MS-based approaches, high-resolution native MS and targeted glycan profiling, to perform complementary analysis at the intact protein level and released glycan level, respectively. We compared the performance of these methods using samples of engineered half-body IgG4s and a panel of mAbs approved for human use. The glycosylation characterization data derived from these approaches were found to be mutually consistent in composition profiling, and complementary in identification and relative-quantitation of low-abundant uncommon glycoforms. In addition, multiple other sources of micro-heterogeneity, such as glycation, lack of glycosylation, and loss of light chains, could be detected by this approach, and the contribution of multiple types of modifications to the overall micro-heterogeneity could be assessed using our superposition algorithm. Our data demonstrate that the hybrid strategy allows reliable and thorough characterization of mAbs, revealing product characteristics that would easily be missed if only a single approach were used.

Indexed as

Antibodies, MonoclonalHumansImmunoglobulin GMass SpectrometryStructure-Activity RelationshipAntibodies, MonoclonalImmunoglobulin GBevacizumabEculizumabglycosylationIgGInfliximabmAb structural integritynative mass spectrometryOfatumumabPanitumumabRituximabTrastuzumab

Identifiers

PMID28281873
PMCPMC5419080

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LicenceCC BY-NC
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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.