Faster in vivo clearance of human embryonic kidney than Chinese hamster ovary cell derived protein: Role of glycan mediated clearance

Mengmeng Wang; Tetsuya Ishino; Alison Joyce; Amy Tam; Weili Duan; Laura Lin; William S Somers; Ronald Kriz; Denise M O'Hara

doi:10.1016/j.jbiosc.2014.11.008

Faster in vivo clearance of human embryonic kidney than Chinese hamster ovary cell derived protein: Role of glycan mediated clearance

J Biosci Bioeng. 2015 Jun;119(6):657-60. doi: 10.1016/j.jbiosc.2014.11.008. Epub 2015 Jan 6.

Authors

Mengmeng Wang¹, Tetsuya Ishino², Alison Joyce³, Amy Tam², Weili Duan², Laura Lin², William S Somers², Ronald Kriz², Denise M O'Hara³

Affiliations

¹ Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Andover, MA 01810, USA. Electronic address: [email protected].
² Department of Global Biotherapeutics Technologies, Pfizer Inc., Cambridge, MA 02140, USA.
³ Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Andover, MA 01810, USA.

PMID: 25575972
DOI: 10.1016/j.jbiosc.2014.11.008

Abstract

This investigation used in vivo and in vitro tools to study pharmacokinetics and glycosylation of two monomeric antibodies produced either transiently by HEK293 cells or stably by Chinese hamster ovary cells, and demonstrated that higher in vivo clearance of human embryonic kidney antibody was due to higher glycosylation, thus higher mannose receptor mediated uptake.

Keywords: Antibody; Clearance; Glycosylation; Mannan; Mannose receptor; Pharmacokinetics.

MeSH terms

Animals
Antibodies / chemistry*
Antibodies / genetics
Antibodies / metabolism*
Antibody Formation
CHO Cells
Cricetinae
Cricetulus
Glycosylation*
HEK293 Cells
Humans
Kinetics
Lectins, C-Type / metabolism
Mannans / metabolism*
Mannans / pharmacokinetics
Mannose Receptor
Mannose-Binding Lectins / metabolism
Receptors, Cell Surface / metabolism

Substances

Antibodies
Lectins, C-Type
Mannans
Mannose Receptor
Mannose-Binding Lectins
Receptors, Cell Surface