Immune effector cell Fc gamma receptors and complement system (FcγR/Complement)

The immune effector cell Fc gamma receptors (FcγRs) and the complement system are the primary mediators of the therapeutic activity of monoclonal antibodies (mAbs). FcγRs are a diverse group of receptors expressed on the surface of immune cells like natural killer (NK) cells and macrophages that recognize the Fc portion of IgG antibodies, triggering antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) (Nimmerjahn & Ravetch, 2008). The complement system is a network of plasma proteins that can be activated by the same antibody-antigen complexes to form the membrane attack complex, leading to complement-dependent cytotoxicity (CDC) (Ricklin et al., 2010). Together, these systems bridge the adaptive and innate immune responses to eliminate pathogens and tumor cells. In oncology, many successful therapies rely on the robust engagement of these effector mechanisms to achieve clinical efficacy (Vidarsson et al., 2014). However, genetic polymorphisms in FcγRs can lead to variability in patient response, and overactivation of these pathways can result in adverse effects such as cytokine release syndrome or tissue damage (Wang et al., 2018).

Other names

Fc-gamma receptorsComplement systemEffector mechanismsFcγRComplement cascadeEffector function

Therapeutic monoclonal antibodies engage FcγRs on effector cells (e.g., NK cells, macrophages) and C1q in the plasma via their Fc domain to induce target cell death through ADCC, ADCP, and CDC (Wang et al., 2018).