Fig. 4: The mechanism of action underlying the therapeutic efficacy of monoclonal antibodies in multiple myeloma.

Monoclonal antibodies have a variety of modes of action, mainly including antibody-mediated cross-linking induces programmed cell death (PCD) in MM cells; complement-dependent cytotoxicity (CDC) is initiated by the binding of C1q to the Fc tail of the antibody initiates the complement cascade, resulting in formation of the membrane attack complex (MAC); antibody-dependent cell-mediated cytotoxicity (ADCC) is the release of cytoplasmic granzymes and perforin by NK cells after being activated by antibodies, leading to apoptosis of MM cells; antibody-dependent cell-mediated phagocytosis (ADCP) is mainly the phagocytic destruction of MM cells mediated by macrophages; and immunoregulatory actions such as decreasing myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), regulatory B cells (Bregs), and pDCs, which is crucial for the activation of T cells. In addition, monoclonal antibodies can reduce mitochondrial transfer between bone marrow stromal cells (BMSCs) and MM cells, inhibit the function of adhesion molecules, modulate enzymatic activity, and reduce the production of adenosine to inhibit MM cells.