Site-specific antibody-drug conjugate heterogeneity characterization and heterogeneity root cause analysis.

ABSTRACT: Site-specific antibody-drug conjugates (ADCs) are designed to overcome the heterogeneity observed with first-generation ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. Despite significantly enhanced homogeneity, however, the production of site-specific ADCs yields some process-related species heterogeneity, including stereoisomers, unconjugated antibody, underconjugated species, and overconjugated species. An elevated level of size variants, such as heavy chain-light chain species (half ADC), heavy chain-heavy chain-light chain species, and light chain species, is also observed with the final site-specific ADC product. To understand the root cause of heterogeneity generated during the ADC conjugation process, we designed tim

SUBMITTER: Cao M 

PROVIDER: S-EPMC6748582 | biostudies-literature | 2019 Aug/Sep

REPOSITORIES: biostudies-literature