Transient expression of an IL-23R extracellular domain Fc fusion protein in CHO vs. HEK cells results in improved plasma exposure.
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.
Suen
Ka Fai
KF
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Turner
Mary S
MS
Gao
Feng
F
Liu
Bo
B
Althage
Alana
A
Slavin
Anthony
A
Ou
Weijia
W
Zuo
Elizabeth
E
Eckart
Michael
M
Ogawa
Tomohisa
T
Yamada
Masao
M
Tuntland
Tove
T
Harris
Jennifer L
JL
Trauger
John W
JW
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*
C515500:IL23R protein, human; D037102:Lectins; D011961:Receptors, Fc; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins