glycoengineered antibodies

Glycosylation, entailing the covalent attachment of carbohydrate moieties to specific biomolecules, is one of the most common post-translational modification mainly taking place in the endoplasmic reticulum (ER) and Golgi apparatus. About half of all proteins expressed in cells undergo this modification. Glycosylation generally has a major impact on the efficacy and stability of biopharmaceuticals. The CH2 domain of each heavy chain contains one conserved N-glycosylation site at Asn297, and approximately 1/5 of human IgGs have a second N-glycosylation motif in the variable region. Antibody glycoengineering is being developed as a method to control the composition of glycans and to enhance the pharmacological properties of therapeutic antibody, including physical stability, immunogenicity, pharmacokinetics and target recognition. For example, by removal of the core fucose residue from the Fc region of the antibody, the affinity of the antibody for receptors on immune effector cells is increased and the capacity to recruit immune cells, such as macrophages/monocytes and Natural Killer (NK) cells is significantly enhanced. This leads to more effective antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) and thus the capacity of an antibody to trigger the death of targeted cells is improved. Conversely, autoantibody-driven inflammation can be suppressed by addition of terminal sialic acid residues to the Fc glycan.