Method to generate IgG heterodimers that can be used to generate bi-specific monoclonal antibodies for disease treatment.
Antibodies are essential therapeutic modalities for treating many diseases, including cancer, autoimmune disorders, degenerative diseases, and inflammation. Bi-specific antibodies are antibodies with two binding sites, meaning they can engage two disease targets with one molecule. Bi-specific antibodies have broad applications for the treatment of various diseases. The FDA approved the first antibody over three decades ago, and since more than 570 have been studied in clinical trials, over 80 have been FDA-approved. Although antibodies have changed how many diseases are treated, they still have several limitations, including intracellular targeting, undruggable targets, protein-protein interactions, etc. Additionally, current manufacturing practices are inefficient and timely, requiring months to generate sufficient quantities of drugs and years to obtain FDA approval.
Researchers at Emory have developed a novel method for identifying and generating new monoclonal antibodies. It involves an in silico approach to enable IgG heterodimer formation using CH3-CH3 residue mutations which identified 31 novel mutations. The mutations were then introduced into the heavy chain (Hc) constructs of Rituximab, an FDA-approved chemotherapy. Data generated by the inventors showed their mutations promote the efficient formation of multiple IgG heterodimers that are more stable and homogeneous than previously produced IgG heterodimers.
Pre-clinical stage of development.