title: Approaches to Interchain Cysteine-Linked ADC Characterization by Mass Spectrometry.
abstract: Therapeutic antibody-drug conjugates (ADCs) harness the cell-killing potential of cytotoxic agents and the tumor targeting specificity of monoclonal antibodies to selectively kill tumor cells. Recent years have witnessed the development of several promising modalities that follow the same basic principles of ADC based therapies but which employ unique cytotoxic agents and conjugation strategies in order to realize therapeutic benefit. The complexity and heterogeneity of ADCs present a challenge to some of the conventional analytical methods that industry has relied upon for biologics characterization. This current review will highlight some of the more recent methodological approaches in mass spectrometry that have bridged the gap that is created when conventional analytical techniques provide an incomplete picture of ADC product quality. Specifically, we will discuss mass spectrometric approaches that preserve and/or capture information about the native structure of ADCs and provide unique insights into the higher order structure (HOS) of these therapeutic molecules.
authors.affiliation: Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, Washington 98021, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Valliere-Douglass
authors.affiliation: Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, Washington 98021, United States.
authors.forename: Shawna M
authors.initials: SM
authors.lastname: Hengel
authors.affiliation: Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, Washington 98021, United States.
authors.forename: Lucy Y
authors.initials: LY
authors.lastname: Pan
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000493:pharmacokinetics; D013058:Mass Spectrometry / Q000379:methods*
chemical_list: D018796:Immunoconjugates; D003545:Cysteine
keywords: ADC; HDX-MS; antibody−drug conjugate; auristatin; drug distribution; higher order structure; hydrogen−deuterium exchange; mass spectrometry; pharmacokinetics