ArticleProtein science : a publication of the Protein Society2015
Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.
Article in Protein science : a publication of the Protein Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 135 citations in OpenAlex.
- Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer.The New England journal of medicine · 2020Trial
- Targeting Adaptive and Innate Immune Responses with Covalent Aptamers.Journal of the American Chemical Society · 2026Article
- Focusing on toxicity management: Challenges and strategies for HER2-targeted antibody-drug conjugates in breast cancer.Breast (Edinburgh, Scotland) · 2026Review
- New Frontiers in ADC Analysis: Advances in Chromatography, Electrophoresis, and Mass Spectrometry.The AAPS journal · 2025Review
- To 200,000ACS central science · 2024Article
- Separation and Collision Cross Section Measurements of Protein Complexes Afforded by a Modular Drift Tube Coupled to an Orbitrap Mass Spectrometer.Analytical chemistry · 2022Article
- Combination of IM-Based Approaches to Unravel the Coexistence of Two Conformers on a Therapeutic Multispecific mAb.Analytical chemistry · 2022Article
- Approaches to Heterogeneity in Native Mass Spectrometry.Chemical reviews · 2022Review
- High-Throughput Multi-attribute Analysis of Antibody-Drug Conjugates Enabled by Trapped Ion Mobility Spectrometry and Top-Down Mass Spectrometry.Analytical chemistry · 2021Article
- Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment.Nature cancer · 2021Review
- State-of-the-Art Native Mass Spectrometry and Ion Mobility Methods to Monitor Homogeneous Site-Specific Antibody-Drug Conjugates Synthesis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein.Frontiers in chemistry · 2021Article
- Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress.Journal of clinical medicine · 2020Review
- Investigating the Impact of Sample Preparation on Mass Spectrometry-Based Drug-To-Antibody Ratio Determination for Cysteine- and Lysine-Linked Antibody-Drug Conjugates.Antibodies (Basel, Switzerland) · 2020Article
- High Mass Analysis with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: From Inorganic Salt Clusters to Antibody Conjugates and Beyond.Journal of the American Society for Mass Spectrometry · 2020Article
- Rapid and Simultaneous Characterization of Drug Conjugation in Heavy and Light Chains of a Monoclonal Antibody Revealed by High-Resolution Ion Mobility Separations in SLIM.Analytical chemistry · 2020Article
- Rapid online buffer exchange for screening of proteins, protein complexes and cell lysates by native mass spectrometry.Nature protocols · 2020Article
- Relating glycoprotein structural heterogeneity to function - insights from native mass spectrometry.Current opinion in structural biology · 2019Review
- Solvent Mediation of Peptide Conformations: Polyproline Structures in Water, Methanol, Ethanol, and 1-Propanol as Determined by Ion Mobility Spectrometry-Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2019Article
- Signature of Antibody Domain Exchange by Native Mass Spectrometry and Collision-Induced Unfolding.Analytical chemistry · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1.
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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.