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Journal articles
IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions.
Chang-Han Lee
1
Gabrielle Romain
2
Wupeng Yan
2
Makiko Watanabe
1
Wissam Charab
1
Biliana Todorova
3
Jiwon Lee
1
Kendra Triplett
1
Moses Donkor
1
Oana Lungu
1
Anja Lux
4
Nicholas Marshall
1
Margaret Lindorfer
5
Odile Richard-Le Goff
3
Bianca Balbino
3, 6
Tae Hyun Kang
1
Hidetaka Tanno
1
George Delidakis
1
Corrine Alford
1
Ronald Taylor
7
Falk Nimmerjahn
4
Navin Varadarajan
2
Pierre Bruhns
3
Yan Jessie Zhang
1
George Georgiou
1
Margaret Lindorfer 5
Author
Odile Richard-Le Goff 3
Author IdHAL : odile-richard-le-goff ORCID : https://orcid.org/0000-0002-6263-2375
Bianca Balbino 3, 6
Author
Tae Hyun Kang 1
Author
Falk Nimmerjahn 4
Author
Navin Varadarajan 2
Author
Pierre Bruhns 3
Author IdHAL : pierre-bruhns ResearcherId : http://www.researcherid.com/rid/F-5567-2013 ORCID : https://orcid.org/0000-0002-4709-8936
Yan Jessie Zhang 1
Author
George Georgiou 1
Author
1
University of Texas at Austin [Austin] (1 University Station Austin, Texas 78712 - United States)
2
University of Houston ( Houston, TX 77204 - United States)
3
Anticorps en Thérapie et Pathologie (25-28 rue du Docteur Roux F-75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U760 (101, rue de Tolbiac, 75013 Paris - France)
4
FAU - Friedrich-Alexander Universität Erlangen-Nürnberg (Schlossplatz 4, 91054 Erlangen, Germany - Germany)
5
University of Virginia School of Medicine [US] (1215 Lee St # 4580, Charlottesville, VA 22908 - United States)
6
UPMC - Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (4 place Jussieu - 75005 Paris - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
7
xxx - University of Virginia, Department of Biochemistry and Molecular Genetics (Charlottesville, VA 22908-0733 - United States)
- University of Virginia [Charlottesville] (P.O. Box 400229, Charlottesville, VA 22904-4229 - United States)
Abstract : Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.
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Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02510289
Contributor : Marie Martin Connect in order to contact the contributor
Submitted on : Tuesday, March 17, 2020 - 4:14:27 PM
Last modification on : Tuesday, November 16, 2021 - 4:24:02 PM
Contributor : Marie Martin Connect in order to contact the contributor
Submitted on : Tuesday, March 17, 2020 - 4:14:27 PM
Last modification on : Tuesday, November 16, 2021 - 4:24:02 PM
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- HAL Id : pasteur-02510289, version 1
- DOI : 10.1038/ni.3770
- PUBMED : 28604720
- PUBMEDCENTRAL : PMC6015732
Citation
Chang-Han Lee, Gabrielle Romain, Wupeng Yan, Makiko Watanabe, Wissam Charab, et al.. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions.. Nature Immunology, Nature Publishing Group, 2017, 18 (8), pp.889-898. ⟨10.1038/ni.3770⟩. ⟨pasteur-02510289⟩
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