In-Depth Structure and Function Characterization of Heterogeneous Interchain Cysteine-Conjugated Antibody-Drug Conjugates.

ABSTRACT: Antibody-drug conjugates (ADCs), integrating high specificity of antigen-targeting antibodies and high potency of cell-killing chemical drugs, have become one of the most rapidly expanding therapeutic biologics in oncology. Although ADCs were widely studied from multiple aspects, overall structural elucidation with comprehensive understanding of variants is scarcely reported. Here, for the first time, we present a holistic and in-depth characterization of an interchain cysteine-conjugated ADC, focusing on conjugation and charge heterogeneity, and in vitro biological activities. Conjugation mapping utilized a bottom-up approach, unraveled positional isomer composition, provided insights into the conjugation process, and elucidated how conjugation affects the physicochemical and biological p

SUBMITTER: Chen H 

PROVIDER: S-EPMC10789146 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature