Immune effector function in multiple myeloma

Immune effector function in multiple myeloma is not a single molecular target but a complex physiological process involving the recruitment and activation of the host immune system to eliminate malignant plasma cells (Nijhof et al., 2016). This process serves as the fundamental mechanism of action for several classes of immunotherapy, including monoclonal antibodies, bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies (van de Donk & Plesner, 2016). Therapeutic agents such as daratumumab and elotuzumab enhance these functions by inducing antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) through interactions with Natural Killer (NK) cells and macrophages (Tai & Anderson, 2015). In the immunosuppressive bone marrow microenvironment of multiple myeloma, these effector functions are often impaired, necessitating treatments that can redirect T cells or overcome immune exhaustion (Cho et al., 2018). While highly effective in clinical practice, the potent activation of these immune pathways can lead to significant adverse events, most notably cytokine release syndrome (CRS) and neurotoxicity (Lee et al., 2019).

Other names

Immune-mediated cytotoxicityAntibody-dependent cellular cytotoxicity (ADCC)Antibody-dependent cellular phagocytosis (ADCP)Complement-dependent cytotoxicity (CDC)T-cell redirection

Immune effector functions are activated through the binding of therapeutic antibodies to tumor antigens (e.g., CD38, BCMA), which subsequently recruit effector cells like NK cells and macrophages via Fc-gamma receptor interactions to induce ADCC and ADCP, or activate the complement cascade for CDC (Nijhof et al., 2016). Bispecific antibodies and CAR-T cells bypass traditional MHC restriction to directly activate T-cell mediated lysis of myeloma cells (van de Donk & Plesner, 2016).