Quantitative cumulative biodistribution of antibodies in mice: effect of modulating binding affinity to the neonatal Fc receptor.

作者: Victor Yip , Enzo Palma , Devin B Tesar , Eduardo E Mundo , Daniela Bumbaca

DOI: 10.4161/MABS.28254

关键词: AntibodyChinese hamster ovary cellGlycoproteinBiodistributionBiologyImmunoglobulin GNeonatal Fc receptorHerpes simplex virusMolecular biologyPharmacokinetics

摘要: The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling endothelial hematopoietic cells thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn’s metabolism IgG within individual tissues after intravenous administration. To elucidate organ distribution gain insight into humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies normal CD-1 mice were conducted. Here, we generated variants herpes simplex virus glycoprotein D-specific (humanized anti-gD) increased decreased FcRn affinity by genetic engineering without affecting antigen specificity. These expressed Chinese hamster ovary cell lines, purified paired radiolabeled iodine-125 indium-111. Equal amounts I-125-labeled In-111-labeled mixed intravenously administ...

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