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Article Dans Une Revue Expert Review of Proteomics Année : 2016

Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates

Résumé

Antibody drug conjugates (ADCs) are highly cytotoxic drugs covalently attached via conditionally stable linkers to monoclonal antibodies (mAbs) and are among the most promising next-generation empowered biologics for cancer treatment. ADCs are more complex than naked mAbs, as the heterogeneity of the conjugates adds to the inherent microvariability of the biomolecules. The development and optimization of ADCs rely on improving their analytical and bioanalytical characterization by assessing several critical quality attributes, namely the distribution and position of the drug, the amount of naked antibody, the average drug to antibody ratio, and the residual druglinker and related product proportions. Here brentuximab vedotin (Adcetris®) and trastuzumab emtansine (Kadcyla®), the first and gold-standard hinge-cysteine and lysine drug conjugates, respectively, were chosen to develop new mass spectrometry (MS) methods and to improve multiplelevel structural assessment protocols.
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Dates et versions

hal-02335539 , version 1 (19-03-2021)

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Alain Beck, Guillaume Terral, François Debaene, Elsa Wagner-Rousset, Julien Marcoux, et al.. Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates. Expert Review of Proteomics, 2016, 13 (2), pp.157-183. ⟨10.1586/14789450.2016.1132167⟩. ⟨hal-02335539⟩
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