Nature Communications (Nov 2019)
An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence
- Chang-Han Lee,
- Tae Hyun Kang,
- Ophélie Godon,
- Makiko Watanabe,
- George Delidakis,
- Caitlin M. Gillis,
- Delphine Sterlin,
- David Hardy,
- Michel Cogné,
- Lynn E. Macdonald,
- Andrew J. Murphy,
- Naxin Tu,
- Jiwon Lee,
- Jonathan R. McDaniel,
- Emily Makowski,
- Peter M. Tessier,
- Aaron S. Meyer,
- Pierre Bruhns,
- George Georgiou
Affiliations
- Chang-Han Lee
- Department of Chemical Engineering, University of Texas at Austin
- Tae Hyun Kang
- Department of Chemical Engineering, University of Texas at Austin
- Ophélie Godon
- Unit of Antibodies in Therapy and Pathology, Institut Pasteur
- Makiko Watanabe
- Department of Chemical Engineering, University of Texas at Austin
- George Delidakis
- Department of Chemical Engineering, University of Texas at Austin
- Caitlin M. Gillis
- Unit of Antibodies in Therapy and Pathology, Institut Pasteur
- Delphine Sterlin
- Unit of Antibodies in Therapy and Pathology, Institut Pasteur
- David Hardy
- Experimental Neuropathology Unit, Infection and Epidemiology Department, Institut Pasteur
- Michel Cogné
- Limoges University
- Lynn E. Macdonald
- Regeneron Pharmaceuticals, Inc.
- Andrew J. Murphy
- Regeneron Pharmaceuticals, Inc.
- Naxin Tu
- Regeneron Pharmaceuticals, Inc.
- Jiwon Lee
- Thayer School of Engineering, Dartmouth College
- Jonathan R. McDaniel
- Department of Chemical Engineering, University of Texas at Austin
- Emily Makowski
- Department of Pharmaceutical Sciences, University of Michigan
- Peter M. Tessier
- Department of Chemical Engineering, University of Michigan
- Aaron S. Meyer
- Department of Bioengineering, University of California at Los Angeles
- Pierre Bruhns
- Unit of Antibodies in Therapy and Pathology, Institut Pasteur
- George Georgiou
- Department of Chemical Engineering, University of Texas at Austin
- DOI
- https://doi.org/10.1038/s41467-019-13108-2
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 11
Abstract
Lee et al. report an engineered IgG1 Fc domain that behaves like an hFcRn binding pH toggle switch. The authors show that this new half-life extension Fc domain confers improved pharmacokinetics in new humanized knock-in mouse strains that recapitulate the key processes for antibody persistence in circulation.
