ArticlemAbs2017
Insights from native mass spectrometry approaches for top- and middle- level characterization of site-specific antibody-drug conjugates.
Article in mAbs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- New Frontiers in ADC Analysis: Advances in Chromatography, Electrophoresis, and Mass Spectrometry.The AAPS journal · 2025Review
- Homogeneous multi-payload antibody-drug conjugates.Nature chemistry · 2024Review
- Enhanced Characterization of Lysine-Linked Antibody Drug Conjugates Enabled by Middle-Down Mass Spectrometry and Higher-Energy Collisional Dissociation-Triggered Electron-Transfer/Higher-Energy Collisional Dissociation and Ultraviolet Photodissociation.Antibodies (Basel, Switzerland) · 2024Article
- Development of an Automated, High-Throughput Methodology for Native Mass Spectrometry and Collision-Induced Unfolding.Analytical chemistry · 2023Article
- Mass spectrometric insights into protein aggregation.Essays in biochemistry · 2023Review
- Online Collision-Induced Unfolding of Therapeutic Monoclonal Antibody Glyco-Variants through Direct Hyphenation of Cation Exchange Chromatography with Native Ion Mobility-Mass Spectrometry.Analytical chemistry · 2023Article
- Combination of IM-Based Approaches to Unravel the Coexistence of Two Conformers on a Therapeutic Multispecific mAb.Analytical chemistry · 2022Article
- Monitoring In Vivo Performances of Protein-Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging.Journal of medicinal chemistry · 2022Article
- High-Resolution Native Mass Spectrometry.Chemical reviews · 2022Review
- Template directed synthesis of antibody Fc conjugates with concomitant ligand release.Chemical science · 2022Article
- Studying protein structure and function by native separation-mass spectrometry.Nature reviews. Chemistry · 2022Review
- Rapid Analysis of Biotherapeutics Using Protein A Chromatography Coupled to Orbitrap Mass Spectrometry.Analytical chemistry · 2021Article
- High-Throughput Multi-attribute Analysis of Antibody-Drug Conjugates Enabled by Trapped Ion Mobility Spectrometry and Top-Down Mass Spectrometry.Analytical chemistry · 2021Article
- State-of-the-Art Native Mass Spectrometry and Ion Mobility Methods to Monitor Homogeneous Site-Specific Antibody-Drug Conjugates Synthesis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Article
- Analytical Methods for the Detection and Quantification of ADCs in Biological Matrices.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Rapid Analysis of Reduced Antibody Drug Conjugate by Online LC-MS/MS with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.Analytical chemistry · 2020Article
- Current LC-MS-based strategies for characterization and quantification of antibody-drug conjugates.Journal of pharmaceutical analysis · 2020Review
- 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
- Antibody-Drug Conjugates Targeting the Urokinase Receptor (uPAR) as a Possible Treatment of Aggressive Breast Cancer.Antibodies (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) have emerged as a family of compounds with promise as efficient immunotherapies. First-generation ADCs were generated mostly via reactions on either lysine side-chain amines or cysteine thiol groups after reduction of the interchain disulfide bonds, resulting in heterogeneous populations with a variable number of drug loads per antibody. To control the position and the number of drug loads, new conjugation strategies aiming at the generation of more homogeneous site-specific conjugates have been developed. We report here the first multi-level characterization of a site-specific ADC by state-of-the-art mass spectrometry (MS) methods, including native MS and its hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS methodologies for site-specific ADC analysis, with the unique ability to provide several critical quality attributes within one single run, along with a direct snapshot of ADC homogeneity/heterogeneity without extensive data interpretation. The capabilities of native IM-MS to directly access site-specific ADC conformational information are also highlighted. Finally, the potential of these techniques for assessing an ADC's heterogeneity/homogeneity is illustrated by comparing the analytical characterization of a site-specific DAR4 ADC to that of first-generation ADCs. Altogether, our results highlight the compatibility, versatility, and benefits of native MS approaches for the analytical characterization of all types of ADCs, including site-specific conjugates. Thus, we envision integrating native MS and IM-MS approaches, even in their latest state-of-the-art forms, into workflows that benchmark bioconjugation strategies.
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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.