Recent Advances in Biotechnology

Volume: 3

Antibody Engineering through Fc Glycans for Improved Therapeutic Index

Author(s): Qun Zhou and Huawei Qiu

Pp: 152-171 (20)

DOI: 10.2174/9781681083919116030009

* (Excluding Mailing and Handling)


The N-glycans from Asn-297 site (or N297 glycans) of antibodies play important roles in antibody function. There is enhanced antibody-dependent cellular cytotoxicity (ADCC) with antibodies containing non-fucosylated glycans, while high anti-inflammatory activity was observed with the antibodies having highly sialylated biantennary structure. Many different approaches have been applied to engineer the N297 glycans with various structures to improve therapeutic efficacy by increasing antibody function, including pro-inflammatory effector function for cancer or antiviral therapy and anti-inflammatory activity for autoimmune diseases. Furthermore, the involvement of various N297 glycan forms in antibody structure-function relationship has also been recently elucidated. The crystal structures of FcγRIIIA complexed with non-fucosylated Fc demonstrated a more favorable carbohydrate-carbohydrate interaction, which is required for high affinity binding and enhanced ADCC activity. The strong anti-inflammatory activity of highly sialylated antibody is related to its interaction with dendritic cell specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). In addition, the N297 glycans were also remodeled for sitespecific antibody conjugation. Thus, antibody glycoengineering provides valuable approaches for modulating antibody function, leading to increased therapeutic index.

Keywords: ADCC, Anti-inflammatory activity, Antibody-dependent cellular cytotoxicity, Autoimmune diseases, Bisecting GlcNAc containing glycans, Cancer, CDC, Complement-dependent cytotoxicity, Dendritic cell specific intercellular adhesion molecule-3-grabbing nonintegrin, FcγRIIIA, Glycoengineering, High mannose-type glycans, Highly galactosylated glycans, Highly sialylated glycans, Homogeneous and site-specific ADC, N-glycans, N297 glycans, Non-fucosylated glycans, Site-specific antibody conjugation, Therapeutic antibodies.

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