title: Optimization of humanized IgGs in glycoengineered Pichia pastoris.
abstract: 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.
authors.affiliation: GlycoFi Inc. 21 Lafayette Street, Lebanon, New Hampshire 03766, USA.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Li
authors.forename: Natarajan
authors.initials: N
authors.lastname: Sethuraman
authors.forename: Terrance A
authors.initials: TA
authors.lastname: Stadheim
authors.forename: Dongxing
authors.initials: D
authors.lastname: Zha
authors.forename: Bianka
authors.initials: B
authors.lastname: Prinz
authors.forename: Nicole
authors.initials: N
authors.lastname: Ballew
authors.forename: Piotr
authors.initials: P
authors.lastname: Bobrowicz
authors.forename: Byung-Kwon
authors.initials: BK
authors.lastname: Choi
authors.forename: W James
authors.initials: WJ
authors.lastname: Cook
authors.forename: Michael
authors.initials: M
authors.lastname: Cukan
authors.forename: Nga Rewa
authors.initials: NR
authors.lastname: Houston-Cummings
authors.forename: Robert
authors.initials: R
authors.lastname: Davidson
authors.forename: Bing
authors.initials: B
authors.lastname: Gong
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: Jack P
authors.initials: JP
authors.lastname: Hoopes
authors.forename: Youwei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Nam
authors.initials: N
authors.lastname: Kim
authors.forename: Renee
authors.initials: R
authors.lastname: Mansfield
authors.forename: Juergen H
authors.initials: JH
authors.lastname: Nett
authors.forename: Sandra
authors.initials: S
authors.lastname: Rios
authors.forename: Rendall
authors.initials: R
authors.lastname: Strawbridge
authors.forename: Stefan
authors.initials: S
authors.lastname: Wildt
authors.forename: Tillman U
authors.initials: TU
authors.lastname: Gerngross
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins