Nature Biotechnology 23, 1283 - 1288 (2005)
Published online: 25 September 2005; | doi:10.1038/nbt1143
Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levelsCarlos Vaccaro1, Jinchun Zhou1, Raimund J Ober1, 2
& E Sally Ward11
Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, Texas
75390-9093, USA. 2
Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas
75080, USA.
Correspondence should be addressed to E Sally Ward sally.ward@utsouthwestern.edu 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.
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