Fc-engineering for improved cancer immunotherapy

Abstract

Monoclonal antibodies have revolutionized cancer therapy, with approved therapeutics belonging predominantly to the immunoglobulin G (IgG) class. These IgGs mediate antitumor effects predominantly through engagement of Fcγ receptors on immune cells. This engagement results in therapy-activating Fc effector functions such as antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity. Limitations nonetheless include suboptimal effector engagement and adverse immunological side effects. These drawbacks have driven the search for and optimization of Fc-engineering strategies, including Fc mutations, glycan modification, and choice of Ig isotype, to enhance therapeutic efficacy and tailor immune interactions.