ArticlemAbs2016
Full validation of therapeutic antibody sequences by middle-up mass measurements and middle-down protein sequencing.
Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
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.
Who cites it
31 citing papers in PubMed.
- A Prototype timsOmni Platform Enables Confident Annotation of the Key Hypervariable CDR3 Regions of IgG Immunoglobulins Using Low- and High-Energy Electron-Based Fragmentation.Analytical chemistry · 2026Article
- Applications of Matrix-Assisted Laser Desorption Ionization In-Source Decay Mass Spectrometry.Advances in experimental medicine and biology · 2026Review
- Linker H1 Histone Direct Top-Down Proteoform Analysis.Journal of proteome research · 2025Article
- Direct histone proteoform profiling of the unannotated, endangered coral Acropora cervicornis.Nucleic acids research · 2025Article
- Histone Analysis Using Mobility- and Mass-Selected Ultraviolet Photodissociation in Tandem with Ultra-High-Resolution Mass Spectrometry.Analytical chemistry · 2025Article
- Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025Review
- Analysis of Protein Inhibitors of Trypsin in Quinoa, Amaranth and Lupine Seeds. Selection and Deep Structure-Function Characterization of theInternational journal of molecular sciences · 2025Article
- Direct glycosylation analysis of intact monoclonal antibodies combining ESI MS of glycoforms and MALDI-in source decay MS of glycan fragments.Communications chemistry · 2024Article
- CE-MS/MS and CE-timsTOF to separate and characterize intramolecular disulfide bridges of monoclonal antibody subunits and their application for the assessment of subunit reduction protocols.Analytical and bioanalytical chemistry · 2024Article
- Mass Spectrometry Strategies forCells · 2024Review
- Mass spectrometry characterization of antibodies at the intact and subunit levels: from targeted to large-scale analysis.International journal of mass spectrometry · 2023Article
- Revealing charge heterogeneity of stressed trastuzumab at the subunit level.Analytical and bioanalytical chemistry · 2023Article
- Top-Down Identification and Sequence Analysis of Small Membrane Proteins Using MALDI-MS/MS.Journal of the American Society for Mass Spectrometry · 2022Article
- Use of PASEF for Accelerated Protein Sequence Confirmation and De Novo Sequencing with High Data Quality.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Preparation and characterization of a fully human monoclonal antibody specific for human tumor necrosis factor alpha.Bioengineered · 2021Article
- Structural and Functional Characterization of SARS-CoV-2 RBD Domains Produced in Mammalian Cells.Analytical chemistry · 2021Article
- Proteomic Approaches to Study SARS-CoV-2 Biology and COVID-19 Pathology.Journal of proteome research · 2021Article
- Characterization of Variable Region Genes and Discovery of Key Recognition Sites in the Complementarity Determining Regions of the Anti-Thiacloprid Monoclonal Antibody.International journal of molecular sciences · 2020Article
- Interlaboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2020Article
- Monitoring of immunoglobulin N- and O-glycosylation in health and disease.Glycobiology · 2020Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The regulatory bodies request full sequence data assessment both for innovator and biosimilar monoclonal antibodies (mAbs). Full sequence coverage is typically used to verify the integrity of the analytical data obtained following the combination of multiple LC-MS/MS datasets from orthogonal protease digests (so called "bottom-up" approaches). Top-down or middle-down mass spectrometric approaches have the potential to minimize artifacts, reduce overall analysis time and provide orthogonality to this traditional approach. In this work we report a new combined approach involving middle-up LC-QTOF and middle-down LC-MALDI in-source decay (ISD) mass spectrometry. This was applied to cetuximab, panitumumab and natalizumab, selected as representative US Food and Drug Administration- and European Medicines Agency-approved mAbs. The goal was to unambiguously confirm their reference sequences and examine the general applicability of this approach. Furthermore, a new measure for assessing the integrity and validity of results from middle-down approaches is introduced - the "Sequence Validation Percentage." Full sequence data assessment of the 3 antibodies was achieved enabling all 3 sequences to be fully validated by a combination of middle-up molecular weight determination and middle-down protein sequencing. Three errors in the reference amino acid sequence of natalizumab, causing a cumulative mass shift of only -2 Da in the natalizumab Fd domain, were corrected as a result of this work.
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Registered trials
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.