mAb structure and mechanisms of action. (A) Schematic representation of an IgG antibody consisting of variable (V) and constant (C) domains of the light (L; light grey) and heavy (H; dark grey) chains. The fragment antigen binding (Fab) domain is made up of VL and CL together with VH and CH1, and the fragment crystallizable (Fc) region consists of CH2 and CH3, with an N-glycan attached to CH2. (B) Mechanisms of action of IgG1 mAbs consist of direct effects, including cell death and receptor blockade, and indirect effects, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). ADCC and ADCP are mediated via binding to FcγR and cell death occurs via release of cytotoxic granules and via internalization and degradation of the target, respectively. CDC is mediated via binding to complement protein C1q and cell death occurs via formation of the membrane attack complex (MAC), which consists of complement proteins C5b, C6, C7, and C8 and various copies of C9, and generates pores in the membrane.