Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor.
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.
Cox
Kevin M
KM
Biolex Therapeutics, 158 Credle Street, Pittsboro, North Carolina 27312, USA. kcox@biolex.com
Sterling
Jason D
JD
Regan
Jeffrey T
JT
Gasdaska
John R
JR
Frantz
Karen K
KK
Peele
Charles G
CG
Black
Amelia
A
Passmore
David
D
Moldovan-Loomis
Cristina
C
Srinivasan
Mohan
M
Cuison
Severino
S
Cardarelli
Pina M
PM
Dickey
Lynn F
LF
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*
D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen; D011134:Polysaccharides; D011994:Recombinant Proteins