The integration of antibody engineering with biomolecular interaction visualization tools for the reduction of sequence liabilities in the generation of therapeutic antibodies

Abstract

Monoclonal antibodies are a biological treatment option for hematological cancers that utilize both innovative modalities in conjunction with the function of the immune system. However, limitations with monoclonal antibodies from sequence liabilities in the binding domains can influence stability and manufacturing capabilities. The use of biomolecular interaction visualization tools may offer a theoretical method to modify known sequence liabilities from the binding domains of monoclonal antibodies with little effect on the overall structure and function of the antibody. To investigate this process, two antibodies of interest were selected, and the corresponding antibody sequences were analyzed using a biomolecular interaction visualization tool, altering the observed sequence liabilities. These modifications were assessed using antibody production and binding studies as a single monoclonal antibody, then as a bispecific antibody. A final set of bispecific antibodies were characterized by cell-based binding studies, confirming binding to corresponding cell lines at similar levels as the parental antibody sequences.