title: A common glycan structure on immunoglobulin G for enhancement of effector functions.
abstract: Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan; Department of Chemistry, National Taiwan University, Taipei 106, Taiwan;
authors.forename: Chin-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Ming-Hung
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Shiou-Ting
authors.initials: ST
authors.lastname: Li
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Tsung-I
authors.initials: TI
authors.lastname: Tsai
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Chu
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Ying-Chih
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: Lai
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan;
authors.forename: Yung-Chieh
authors.initials: YC
authors.lastname: Tseng
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Sachin S
authors.initials: SS
authors.lastname: Shivatare
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Wang
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Ping
authors.initials: P
authors.lastname: Chao
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Shi-Yun
authors.initials: SY
authors.lastname: Wang
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Shih
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Zeng
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Tsai-Hong
authors.initials: TH
authors.lastname: You
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Jung-Yu
authors.initials: JY
authors.lastname: Liao
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Tu
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Yih-Shyan
authors.initials: YS
authors.lastname: Lin
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Chuang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chen
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Charng-Sheng
authors.initials: CS
authors.lastname: Tsai
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Chiu-Chen
authors.initials: CC
authors.lastname: Huang
authors.affiliation: CHO Pharma Inc., Taipei 11503, Taiwan;
authors.forename: Nan-Horng
authors.initials: NH
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Che
authors.initials: C
authors.lastname: Ma
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan; chwong@gate.sinica.edu.tw cyiwu@gate.sinica.edu.tw.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan; Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; chwong@gate.sinica.edu.tw cyiwu@gate.sinica.edu.tw.
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity; D001426:Bacterial Proteins / Q000378:metabolism; D001441:Bacteroides fragilis / Q000201:enzymology; D045744:Cell Line, Tumor; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011134:Polysaccharides / Q000737:chemistry*; D015202:Protein Engineering; D017452:Receptors, IgG / Q000276:immunology; D000069283:Rituximab / Q000737:chemistry* / Q000276:immunology; D012794:Sialic Acids / Q000737:chemistry / Q000276:immunology; D013297:Streptococcus pyogenes / Q000201:enzymology; D013329:Structure-Activity Relationship; D000068878:Trastuzumab / Q000737:chemistry / Q000276:immunology; D005644:alpha-L-Fucosidase / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D001426:Bacterial Proteins; C496124:FCGR3A protein, human; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011134:Polysaccharides; D017452:Receptors, IgG; D012794:Sialic Acids; D000069283:Rituximab; C035355:endo-N-acetylneuraminidase; D009439:Neuraminidase; D005644:alpha-L-Fucosidase; D000068878:Trastuzumab; D000117:Acetylglucosamine
keywords: Fc glycosylation; endoglycosidase; glycoengineered antibodies; homogeneous antibodies; sugar oxazoline