title: Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates.
abstract: 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.
authors.affiliation: a Centre d'Immunologie Pierre-Fabre (CIPF) , Saint-Julien-en-Genevois , France.
authors.forename: Alain
authors.initials: A
authors.lastname: Beck
authors.affiliation: b BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC, Analytical Sciences Department , Université de Strasbourg , Strasbourg , France.|c IPHC, Analytical Sciences Department, CNRS, UMR7178 , Strasbourg , France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Terral
authors.affiliation: b BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC, Analytical Sciences Department , Université de Strasbourg , Strasbourg , France.|c IPHC, Analytical Sciences Department, CNRS, UMR7178 , Strasbourg , France.
authors.forename: François
authors.initials: F
authors.lastname: Debaene
authors.affiliation: a Centre d'Immunologie Pierre-Fabre (CIPF) , Saint-Julien-en-Genevois , France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Wagner-Rousset
authors.affiliation: b BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC, Analytical Sciences Department , Université de Strasbourg , Strasbourg , France.|c IPHC, Analytical Sciences Department, CNRS, UMR7178 , Strasbourg , France.
authors.forename: Julien
authors.initials: J
authors.lastname: Marcoux
authors.affiliation: a Centre d'Immunologie Pierre-Fabre (CIPF) , Saint-Julien-en-Genevois , France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Janin-Bussat
authors.affiliation: a Centre d'Immunologie Pierre-Fabre (CIPF) , Saint-Julien-en-Genevois , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Colas
authors.affiliation: b BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC, Analytical Sciences Department , Université de Strasbourg , Strasbourg , France.|c IPHC, Analytical Sciences Department, CNRS, UMR7178 , Strasbourg , France.
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.affiliation: b BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC, Analytical Sciences Department , Université de Strasbourg , Strasbourg , France.|c IPHC, Analytical Sciences Department, CNRS, UMR7178 , Strasbourg , France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cianférani
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D018796:Immunoconjugates / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates
keywords: Antibody-drug-conjugate; IdeS; bioanalysis; brentuximab vedotin; drug-to-antibody ratio; ion mobility MS; mass spectrometry; native MS; trastuzumab emtansine