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.
