期刊
NATURE BIOTECHNOLOGY
卷 23, 期 10, 页码 1283-1288出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt1143
关键词
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资金
- NIAID NIH HHS [R01 AI050747, R01 AI 39167, R01 AI039167, R01 AI 55556, R01 AI 50747, R01 AI055556] Funding Source: Medline
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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