Optimization of humanized IgGs in glycoengineered Pichia pastoris.
As the fastest growing class of therapeutic proteins, monoclonal antibodies (mAbs) represent a major potential drug class. Human antibodies are glycosylated in their native state and all clinically approved mAbs are produced by mammalian cell lines, which secrete mAbs with glycosylation structures that are similar, but not identical, to their human counterparts. Glycosylation of mAbs influences their interaction with immune effector cells that kill antibody-targeted cells. Here we demonstrate that human antibodies with specific human N-glycan structures can be produced in glycoengineered lines of the yeast Pichia pastoris and that antibody-mediated effector functions can be optimized by generating specific glycoforms. Glycoengineered P. pastoris provides a general platform for producing recombinant antibodies with human N-glycosylation.
Li
Huijuan
H
GlycoFi Inc. 21 Lafayette Street, Lebanon, New Hampshire 03766, USA.
Sethuraman
Natarajan
N
Stadheim
Terrance A
TA
Zha
Dongxing
D
Prinz
Bianka
B
Ballew
Nicole
N
Bobrowicz
Piotr
P
Choi
Byung-Kwon
BK
Cook
W James
WJ
Cukan
Michael
M
Houston-Cummings
Nga Rewa
NR
Davidson
Robert
R
Gong
Bing
B
Hamilton
Stephen R
SR
Hoopes
Jack P
JP
Jiang
Youwei
Y
Kim
Nam
N
Mansfield
Renee
R
Nett
Juergen H
JH
Rios
Sandra
S
Strawbridge
Rendall
R
Wildt
Stefan
S
Gerngross
Tillman U
TU
D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics; D024861:Genetic Enhancement / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics*; D010843:Pichia / Q000235:genetics* / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins