Journal Article

A common glycan structure on immunoglobulin G for enhancement of effector functions

Lin, Chin-Wei, Huang, Chiu-Chen, Shivatare, Sachin S., Wang, Shi-Yun, Wu, Chung-Yi, Wang, Chia-Hung, Chao, Ping, Lin, Yih-Shyan, Ma, Che, Wu, Chia-Yu, Wong, Chi-Huey, Li, Shiou-Ting, Tu, Yu-Chen, Zeng, Yi-Fang, You, Tsai-Hong, Liu, Ying-Chih, Chuang, Hong-Yang, Lai, Meng-Yu, Tsai, Charng-Sheng, Tseng, Yung-Chieh, Shih, Hao-Wei, Tsai, Tsung-I, Lin, Nan-Horng, Chu, Kuo-Ching, Liao, Jung-Yu, Chen, Chia-Lin, Tsai, Ming-Hung

2015

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Acetylglucosamine - chemistry / Acetylglucosamine - immunology / alpha-L-Fucosidase - metabolism / Animals / Antibodies, Viral - chemistry / Antibodies, Viral - immunology / Antibodies, Viral - therapeutic use / Antibody-Dependent Cell Cytotoxicity / Bacterial Proteins - metabolism / Bacteroides fragilis - enzymology / Binding sites / Biological Sciences / Cancer / Cell Line, Tumor / Cells / Cytotoxicity / Female / Glycosylation / HEK293 Cells / Humans / Immunoglobulin Fc Fragments - chemistry / Immunoglobulin Fc Fragments - immunology / Immunoglobulin G - chemistry / Immunoglobulin G - immunology / Lymphoma, B-Cell - pathology / Mice / Mice, Inbred BALB C / Neuraminidase - metabolism / Orthomyxoviridae Infections - prevention & control / Physical Sciences / Polysaccharides - chemistry / Protein Engineering / Receptors, IgG - immunology / Rituximab - chemistry / Rituximab - immunology / Sialic Acids - chemistry / Sialic Acids - immunology / Streptococcus pyogenes - enzymology / Structure-Activity Relationship / T cell receptors / Trastuzumab - chemistry / Trastuzumab - immunology