Site-Specific Modification of Native IgGs with Flexible Drug-Load.

ABSTRACT: Homogeneous, site-specifically conjugated antibodies have shown to result in antibody-drug conjugates (ADCs) with improved efficacy and tolerability compared to stochastically conjugated ADCs. However, precisely controlling the drug load as well as attaching multiple payload moieties to the antibody remains challenging. Here, we demonstrate the simple and direct modification of native IgG-antibodies at the residue glutamine 295 (Q295) without the need for any protein engineering with flexible drug-to-antibody ratios of one or multiple payloads. The conjugation is enabled through short, positively charged lysine containing peptides and native, commercially available microbial transglutaminase. In proof-of-concept studies, HER2-targeting ADCs based on trastuzumab were generated with drug-to-

SUBMITTER: Wehrmuller JE 

PROVIDER: S-EPMC12007069 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature