Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels
Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels
We have engineered the Fc region of a human immunoglobulin G (IgG) to generate a mutated antibody that modulates the concentrations of endogenous IgGs in vivo. This has been achieved by targeting the activity of the Fc receptor, FcRn, which serves through its IgG salvage function to maintain and regulate IgG concentrations in the body. We show that an IgG whose Fc region was engineered to bind with higher affinity and reduced pH dependence to FcRn potently inhibits FcRn-IgG interactions and induces a rapid decrease of IgG levels in mice. Such FcRn blockers (or 'Abdegs,' for antibodies that enhance IgG degradation) may have uses in reducing IgG levels in antibody-mediated diseases and in inducing the rapid clearance of IgG-toxin or IgG-drug complexes.
1283-1288
Vaccaro, Carlos
f576072e-379e-4f42-9bd7-595b2f5b7d58
Zhou, Jinchun
373ef03a-4fb7-4022-98c2-7332251c5c30
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
October 2005
Vaccaro, Carlos
f576072e-379e-4f42-9bd7-595b2f5b7d58
Zhou, Jinchun
373ef03a-4fb7-4022-98c2-7332251c5c30
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Vaccaro, Carlos, Zhou, Jinchun, Ober, Raimund J. and Ward, E. Sally
(2005)
Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels.
Nature Biotechnology, 23 (10), .
(doi:10.1038/nbt1143).
Abstract
We have engineered the Fc region of a human immunoglobulin G (IgG) to generate a mutated antibody that modulates the concentrations of endogenous IgGs in vivo. This has been achieved by targeting the activity of the Fc receptor, FcRn, which serves through its IgG salvage function to maintain and regulate IgG concentrations in the body. We show that an IgG whose Fc region was engineered to bind with higher affinity and reduced pH dependence to FcRn potently inhibits FcRn-IgG interactions and induces a rapid decrease of IgG levels in mice. Such FcRn blockers (or 'Abdegs,' for antibodies that enhance IgG degradation) may have uses in reducing IgG levels in antibody-mediated diseases and in inducing the rapid clearance of IgG-toxin or IgG-drug complexes.
This record has no associated files available for download.
More information
Accepted/In Press date: 9 August 2005
e-pub ahead of print date: 25 September 2005
Published date: October 2005
Identifiers
Local EPrints ID: 424093
URI: http://eprints.soton.ac.uk/id/eprint/424093
ISSN: 1087-0156
PURE UUID: a9b026ee-3a68-4dc5-8900-66a4191e3aac
Catalogue record
Date deposited: 04 Oct 2018 16:30
Last modified: 18 Mar 2024 03:48
Export record
Altmetrics
Contributors
Author:
Carlos Vaccaro
Author:
Jinchun Zhou
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
