Site-Specific Conjugation of Native Antibodies Using Engineered Microbial Transglutaminases.

Bioconjugate Chemistry
Stephan DickgiesserNicolas Rasche

Abstract

Site-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.

References

Sep 11, 2002·The Journal of Biological Chemistry·Tatsuki KashiwagiEi-ichiro Suzuki
Jan 24, 2004·Applied Microbiology and Biotechnology·K YokoyamaY Kikuchi
Apr 7, 2005·FEBS Letters·Tsutomu TanakaTeruyuki Nagamune
Jul 22, 2008·Nature Biotechnology·Jagath R JunutulaWilliam Mallet
Dec 24, 2013·Bioconjugate Chemistry·Santiago E FariasArvind Rajpal
May 6, 2014·Bioconjugate Chemistry·George BadescuAntony Godwin
Feb 3, 2015·Bioconjugate Chemistry·Magdalena DorywalskaArvind Rajpal
Nov 21, 2015·Bioconjugate Chemistry·Jan GrunewaldBernhard H Geierstanger
Mar 31, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yusuke OgitaniToshinori Agatsuma
Dec 21, 2016·The Journal of Biological Chemistry·Frederick W JacobsenKannan Gunasekaran
Apr 1, 2017·Advances in Therapy·John M Lambert, Charles Q Morris
Aug 16, 2017·Journal of the American Chemical Society·Jun Ohata, Zachary T Ball
Jan 5, 2018·MAbs·Hélène Kaplon, Janice M Reichert
Feb 24, 2018·Journal of the American Chemical Society·Maria J MatosGonçalo J L Bernardes
Oct 30, 2018·Bioconjugate Chemistry·Chenfei YuHan Xiao
Mar 12, 2019·Angewandte Chemie·Kei YamadaBrian A Mendelsohn
Sep 4, 2019·Chemical Communications : Chem Comm·Cristina MarculescuBart Cornelissen

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Citations

Dec 9, 2020·Chemical Society Reviews·Stephen J WalshDavid R Spring
Mar 2, 2021·Antibody Therapeutics·Amissi SadikiZhaohui Sunny Zhou
Jun 3, 2021·Pharmaceuticals·Vesela KostovaAndras Kotschy
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cristina Bolzati, Barbara Spolaore
Aug 8, 2021·Journal of Pharmaceutical Sciences·Anna KaempffeChristian Schröter

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