Mechanisms of action of monoclonal antibodies targeting surface antigens on MM cells. Monoclonal antibodies against target antigens expressed on MM cells can induce tumor cell killing via Fc-dependent effector mechanisms including CDC, ADCC, and ADCP. The process of ADCC is achieved through activation of Fc receptors on myeloid and NK effector cells by tumor cell-attached immunoglobins. Subsequent cytotoxicity is mediated through ≥2 different mechanisms; one involving the release of perforin and granzymes from effector cells and the other involving death ligands FasL and tumor necrosis factor–related apoptosis-inducing ligand. In ADCP, phagocytosis of tumor cells is mediated by macrophages. CDC is dependent on the interaction of the antibody Fc domains with the classic complement-activating protein C1q leading to activation of downstream complement proteins, which results in the assembly of the membrane attack complex (MAC), that punches holes in the tumor cells. An additional result of this cascade is the production of chemotactic complement molecules C3a and C5a, which recruit and activate immune effector cells. There is also evidence that uptake of antibody-opsonized tumor cells and cellular fragments by antigen-presenting cells is associated with enhanced antigen presentation leading to tumor-specific T-cell responses. Monoclonal antibodies that target antigens on MM cells may also have direct effects via modulation of the activity of the targeted antigen.