Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice.
The neonatal Fc receptor (FcRn) is a homeostatic receptor responsible for prolonging immunoglobulin G (IgG) half-life by protecting it from lysosomal degradation and recycling it to systemic circulation. Tissue-specific FcRn expression is a critical parameter in physiologically-based pharmacokinetic (PBPK) modeling for translational pharmacokinetics of Fc-containing biotherapeutics. Using online peptide immuno-affinity chromatography coupled with high resolution mass spectrometry, we established a quantitative FcRn tissue protein expression profile in human FcRn (hFcRn) transgenic mice, Tg32 homozygous and hemizygous strains. The concentration of hFcRn across 14 tissues ranged from 3.5 to 111.2 pmole per gram of tissue. Our hFcRn quantification data from Tg32 mice will enable a more refined PBPK model to improve the accuracy of human PK predictions for Fc-containing biotherapeutics.
a Pharmacokinetics Dynamics & Metabolism, Pfizer, Inc., Worldwide Research & Development , Andover , Massachusetts , USA.
Yao-Yun
YY
Fan
a Pharmacokinetics Dynamics & Metabolism, Pfizer, Inc., Worldwide Research & Development , Andover , Massachusetts , USA.
Lindsay B
LB
Avery
a Pharmacokinetics Dynamics & Metabolism, Pfizer, Inc., Worldwide Research & Development , Andover , Massachusetts , USA.
Mengmeng
M
Wang
a Pharmacokinetics Dynamics & Metabolism, Pfizer, Inc., Worldwide Research & Development , Andover , Massachusetts , USA.
Denise M
DM
O'Hara
a Pharmacokinetics Dynamics & Metabolism, Pfizer, Inc., Worldwide Research & Development , Andover , Massachusetts , USA.
Sheldon
S
Leung
a Pharmacokinetics Dynamics & Metabolism, Pfizer, Inc., Worldwide Research & Development , Andover , Massachusetts , USA.
Hendrik
H
Neubert
D000818:Animals; D002846:Chromatography, Affinity / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000096:biosynthesis*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D011961:Receptors, Fc / Q000032:analysis* / Q000096:biosynthesis*
D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; C100688:Fc receptor, neonatal
Antibody; IA-LC-HRMS; PBPK models; Tg32; human FcRn; tissue-based target quantification; transgenic mice