The Effector Function Enhancement and Control Technology (EFECT™) platform comprises a library of Fc modifications that can selectively modulate the activity of recruited immune cells including up-regulation to enhance antibody-mediated effector cytotoxicity, and down-regulation to suppress unwanted effector activity for certain therapeutic applications. Proprietary mutations are introduced to the CH2 domain of the antibody's Fc to selectively modulate an antibody’s interactions with the Fc-gamma receptors (FcgR) expressed on the surface of immune cells and with components of the complement pathway (e.g. C1q).
Modulating FcgR engagement tailors antibody effector function to match a specific therapeutic purpose. EFECT™ variants that have selectively increased binding to the FcgRIIIa and/or FcgRIIa receptors display enhanced ADCC (NK-cell driven), ADCP (macrophage driven) and serum clearance of immune complexes. On the other hand, EFECT™ variants with enhanced binding to FcgRIIb can inhibit antibody-mediated auto-immunity by down-regulating immune responses of B cells. In addition, the EFECT™ platform has also been used to ablate binding to all FcgRs and C1q where effector cell-mediated cytotoxicity is undesirable for therapeutic antibodies. For example, ablation of Fc effector function is an important means of ensuring the safety of T cell re-directing bi-specific antibodies and checkpoint inhibitors.