Journal article
The Role of FcRn in Monoclonal Antibody Serum Uptake from the Intestine in Suckling Rat Pups
The FASEB journal, v 27(S1)
Apr 2013
Abstract
Abstract only
The neonatal Fc Receptor (FcRn) in intestinal epithelium is the primary mechanism for transfer of maternal immunoglobulin G (IgG) from suckled milk to serum, but the factors contributing to this rapid uptake are poorly understood. Therefore, the pharmacological characteristics of IgG monoclonal antibody (mAb) and its interactions with FcRn in the intestinal environment in rats were investigated.
Binding affinities to rat FcRn at pH 6.0 and off‐rates of pre‐bound mAb wild type (WT) and variants at pH 7.4 were determined. In anesthetized rats, systemic levels of human (h)IgG were determined after regional intestinal delivery of hIgG variants. Quantification of full‐length mAb in serum, rat FcRn mRNA expression in regions of intestine, and mAb epithelial localization was measured.
High serum levels of hIgG were detected 90 min after duodenal delivery in 2‐week, but not 4–8 week old rats. Serum levels of variants correlated with off‐rates, not FcRn affinity. Serum levels of WT mAb, administered to different regions of intestine, correlated with rFcRn mRNA regional expression.
The suckling rat pup intestine is an ideal mechanistic model of FcRn‐IgG mediated transcytosis. While binding affinity to FcRn is important for obtaining serum levels, a variant with a faster off‐rate at pH 7.4 than WT resulted in greater serum levels.
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Details
- Title
- The Role of FcRn in Monoclonal Antibody Serum Uptake from the Intestine in Suckling Rat Pups
- Creators
- Philip R Cooper - JanssenConnie Kliwinski - JanssenRobert Perkinson - JanssenJohn Mabus - JanssenJill Giles-Komar - United States Army Corps of EngineersPamela Hornby - Janssen
- Publication Details
- The FASEB journal, v 27(S1)
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Other Identifier
- 991021931775604721