Interrogating heterogeneity of cysteine-engineered antibody-drug conjugates and antibody-oligonucleotide conjugates by capillary zone electrophoresis-mass spectrometry.

ABSTRACT: Production of site-specific cysteine-engineered antibody-drug conjugates (ADCs) in mammalian cells may produce developability challenges, fragments, and heterogenous molecules, leading to potential product critical quality attributes in later development stages. Liquid phase chromatography with mass spectrometry (LC-MS) is widely used to evaluate antibody impurities and drug-to-antibody ratio, but faces challenges in analysis of fragment product variants of cysteine-engineered ADCs and oligonucleotide-to-antibody ratio (OAR) species of antibody-oligonucleotide conjugates (AOCs). Here, for the first time, we report novel capillary zone electrophoresis (CZE)-MS approaches to address the challenges above. CZE analysis of six ADCs made with different parent monoclonal antibodies (mAbs) and sma

SUBMITTER: Xu T 

PROVIDER: S-EPMC10312020 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature