Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates.
Fiche publication
Date publication
janvier 2016
Journal
Expert review of proteomics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah, Dr VAN DORSSELAER Alain
Tous les auteurs :
Beck A, Terral G, Debaene F, Wagner-Rousset E, Marcoux J, Janin-Bussat MC, Colas O, Van Dorsselaer A, Cianférani S
Lien Pubmed
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 drug-linker 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 multiple-level structural assessment protocols.
Mots clés
Antibodies, Monoclonal, immunology, Immunoconjugates, chemistry, Mass Spectrometry, methods
Référence
Expert Rev Proteomics. 2016 ;13(2):157-83