A method to produce asymmetrically glycosylated antibodies for the treatment and prevention of diseases including cancer, auto-immune disorders, and infectious diseases.
Monoclonal antibodies are widely used therapeutics for treating diseases such as cancer, autoimmune disorders, degenerative conditions, and inflammation. Despite their impact, they face limitations, including difficulty targeting intracellular or “undruggable” proteins and modulating protein–protein interactions. Immunoglobulin G (IgG), which accounts for 70–75% of circulating antibodies, mediates immune responses through interactions between its Fc region and Fc gamma receptors (FcγRs) on immune cells, leading to activating or inhibitory effects. Recent studies have shown that asymmetrically glycosylated IgG antibodies, or those antibodies with distinct glycans on each of their two Fc region protomers, are a universal and prevalent feature of human immunology that drive distinctive antibody-mediated effector functions. Accordingly, methods to engineer asymmetrically glycosylated antibodies will produce a new class of IgG antibodies with precisely controlled effector functions and improved therapeutic performance.
Inventors at Emory University have developed methods to produce asymmetrically glycosylated IgG antibodies that can represent a new class of therapeutic monoclonal antibodies for the treatment or prevention of a disease. The proposed strategy can be expanded to engineer any possible combination of asymmetrically glycosylated IgG antibodies. Antibodies generated using the proposed method could result in proteins with unique therapeutic potential.