bc0c00061_si_001.pdf (1.54 MB)
Site-Specific Conjugation of Native Antibodies Using Engineered Microbial Transglutaminases
journal contribution
posted on 2020-03-12, 14:33 authored by Stephan Dickgiesser, Marcel Rieker, Dirk Mueller-Pompalla, Christian Schröter, Jason Tonillo, Shira Warszawski, Sabine Raab-Westphal, Stefanie Kühn, Tim Knehans, Doreen Könning, Julia Dotterweich, Ulrich A. K. Betz, Jan Anderl, Stefan Hecht, Nicolas RascheSite-specific
bioconjugation technologies are frequently employed
to generate homogeneous antibody–drug conjugates (ADCs) and
are generally considered superior to stochastic approaches like lysine
coupling. However, most of the technologies developed so far require
undesired manipulation of the antibody sequence or its glycan structures.
Herein, we report the successful engineering of microbial transglutaminase
enabling efficient, site-specific conjugation of drug-linker constructs
to position HC-Q295 of native, fully glycosylated IgG-type antibodies.
ADCs generated via this approach demonstrate excellent stability in vitro as well as strong efficacy in vitro and in vivo. As it employs different drug-linker
structures and several native antibodies, our study additionally proves
the broad applicability of this approach.