Nature Communications (Mar 2023)
An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity
- Nina E. Weisser,
- Mario Sanches,
- Eric Escobar-Cabrera,
- Jason O’Toole,
- Elizabeth Whalen,
- Peter W. Y. Chan,
- Grant Wickman,
- Libin Abraham,
- Kate Choi,
- Bryant Harbourne,
- Antonios Samiotakis,
- Andrea Hernández Rojas,
- Gesa Volkers,
- Jodi Wong,
- Claire E. Atkinson,
- Jason Baardsnes,
- Liam J. Worrall,
- Duncan Browman,
- Emma E. Smith,
- Priya Baichoo,
- Chi Wing Cheng,
- Joy Guedia,
- Sohyeong Kang,
- Abhishek Mukhopadhyay,
- Lisa Newhook,
- Anders Ohrn,
- Prajwal Raghunatha,
- Matteo Zago-Schmitt,
- Joseph D. Schrag,
- Joel Smith,
- Patricia Zwierzchowski,
- Joshua M. Scurll,
- Vincent Fung,
- Sonia Black,
- Natalie C. J. Strynadka,
- Michael R. Gold,
- Leonard G. Presta,
- Gordon Ng,
- Surjit Dixit
Affiliations
- Nina E. Weisser
- Zymeworks BC Inc.
- Mario Sanches
- Zymeworks BC Inc.
- Eric Escobar-Cabrera
- Zymeworks BC Inc.
- Jason O’Toole
- Zymeworks BC Inc.
- Elizabeth Whalen
- Zymeworks BC Inc.
- Peter W. Y. Chan
- Zymeworks BC Inc.
- Grant Wickman
- Zymeworks BC Inc.
- Libin Abraham
- Department of Microbiology and Immunology, University of British Columbia
- Kate Choi
- Department of Microbiology and Immunology, University of British Columbia
- Bryant Harbourne
- Zymeworks BC Inc.
- Antonios Samiotakis
- Zymeworks BC Inc.
- Andrea Hernández Rojas
- Zymeworks BC Inc.
- Gesa Volkers
- Zymeworks BC Inc.
- Jodi Wong
- Zymeworks BC Inc.
- Claire E. Atkinson
- Department of Biochemistry and Molecular Biology, University of British Columbia
- Jason Baardsnes
- Human Health Therapeutics Portfolio, NRC-CNRC
- Liam J. Worrall
- Department of Biochemistry and Molecular Biology, University of British Columbia
- Duncan Browman
- Zymeworks BC Inc.
- Emma E. Smith
- Human Health Therapeutics Portfolio, NRC-CNRC
- Priya Baichoo
- Zymeworks BC Inc.
- Chi Wing Cheng
- Zymeworks BC Inc.
- Joy Guedia
- Zymeworks BC Inc.
- Sohyeong Kang
- Zymeworks BC Inc.
- Abhishek Mukhopadhyay
- Zymeworks BC Inc.
- Lisa Newhook
- Zymeworks BC Inc.
- Anders Ohrn
- Zymeworks BC Inc.
- Prajwal Raghunatha
- Zymeworks BC Inc.
- Matteo Zago-Schmitt
- Zymeworks BC Inc.
- Joseph D. Schrag
- Human Health Therapeutics Portfolio, NRC-CNRC
- Joel Smith
- Zymeworks BC Inc.
- Patricia Zwierzchowski
- Zymeworks BC Inc.
- Joshua M. Scurll
- Department of Mathematics and Institute of Applied Mathematics, University of British Columbia
- Vincent Fung
- Zymeworks BC Inc.
- Sonia Black
- Zymeworks BC Inc.
- Natalie C. J. Strynadka
- Department of Biochemistry and Molecular Biology, University of British Columbia
- Michael R. Gold
- Department of Microbiology and Immunology, University of British Columbia
- Leonard G. Presta
- Zymeworks BC Inc.
- Gordon Ng
- AbbVie
- Surjit Dixit
- Zymeworks BC Inc.
- DOI
- https://doi.org/10.1038/s41467-023-37029-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 22
Abstract
The success of HER2-targeted cancer therapy is limited by treatment resistance. Here, the authors engineer an anti-HER2 biparatopic antibody with multiple mechanisms of action including induction of HER2 clustering to trigger complement dependent cytotoxicity, signal inhibition, antibody dependent cellular cytotoxicity and phagocytosis.
