title: Transient expression of an IL-23R extracellular domain Fc fusion protein in CHO vs. HEK cells results in improved plasma exposure.
abstract: Transient transfection of mammalian cells in suspension culture has recently emerged as a very useful method for production of research-scale quantities of recombinant proteins. The most commonly used cell lines for this purpose are suspension-adapted HEK and CHO cells. We report here that the plasma exposure in mice of an IL-23R extracellular domain Fc fusion protein (IL23R-Fc) differed dramatically depending on whether the protein was prepared by transient transfection of HEK or CHO cells. Specifically, IL23R-Fc expressed using CHO cells had about 30-fold higher in vivo plasma exposure compared to the HEK-expressed protein. In contrast to their differing plasma exposures, the HEK- and CHO-expressed proteins had equivalent in vitro biological activity. Characterization of the CHO- and HEK-expressed IL23R-Fc proteins indicated that the differences in in vivo plasma exposure between them are due to differential glycosylation.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: Suen
authors.forename: Mary S
authors.initials: MS
authors.lastname: Turner
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Alana
authors.initials: A
authors.lastname: Althage
authors.forename: Anthony
authors.initials: A
authors.lastname: Slavin
authors.forename: Weijia
authors.initials: W
authors.lastname: Ou
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zuo
authors.forename: Michael
authors.initials: M
authors.lastname: Eckart
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Ogawa
authors.forename: Masao
authors.initials: M
authors.lastname: Yamada
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harris
authors.forename: John W
authors.initials: JW
authors.lastname: Trauger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004591:Electrophoresis, Polyacrylamide Gel; D005110:Extracellular Space / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007525:Isoelectric Focusing; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000097:blood* / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods*
chemical_list: C515500:IL23R protein, human; D037102:Lectins; D011961:Receptors, Fc; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins