title: Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor.
abstract: N-glycosylation is critical to the function of monoclonal antibodies (mAbs) and distinguishes various systems used for their production. We expressed human mAbs in the small aquatic plant Lemna minor, which offers several advantages for manufacturing therapeutic proteins free of zoonotic pathogens. Glycosylation of a mAb against human CD30 was optimized by co-expressing the heavy and light chains of the mAb with an RNA interference construct targeting expression of the endogenous alpha-1,3-fucosyltransferase and beta-1,2-xylosyltransferase genes. The resultant mAbs contained a single major N-glycan species without detectable plant-specific N-glycans and had better antibody-dependent cell-mediated cytotoxicity and effector cell receptor binding activities than mAbs expressed in cultured Chinese hamster ovary (CHO) cells.
authors.affiliation: Biolex Therapeutics, 158 Credle Street, Pittsboro, North Carolina 27312, USA. kcox@biolex.com
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Cox
authors.forename: Jason D
authors.initials: JD
authors.lastname: Sterling
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Regan
authors.forename: John R
authors.initials: JR
authors.lastname: Gasdaska
authors.forename: Karen K
authors.initials: KK
authors.lastname: Frantz
authors.forename: Charles G
authors.initials: CG
authors.lastname: Peele
authors.forename: Amelia
authors.initials: A
authors.lastname: Black
authors.forename: David
authors.initials: D
authors.lastname: Passmore
authors.forename: Cristina
authors.initials: C
authors.lastname: Moldovan-Loomis
authors.forename: Mohan
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Severino
authors.initials: S
authors.lastname: Cuison
authors.forename: Pina M
authors.initials: PM
authors.lastname: Cardarelli
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Dickey
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D029064:Araceae / Q000235:genetics / Q000378:metabolism*; D001709:Biotechnology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology; D030821:Plants, Genetically Modified / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*; D014176:Protein Biosynthesis / Q000276:immunology*; D034622:RNA Interference / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis*
chemical_list: D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen; D011134:Polysaccharides; D011994:Recombinant Proteins