Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma

Abstract

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR)-T cells. In this review, we will highlight the mechanism of action of immuno-therapy currently available in clinical practice to target CD38, SLAMF7, and BCMA, focusing on the biological role of the targets and on mechanisms of actions of the different immunotherapeutic approaches underlying their advantages and disadvantages with critical review of the literature data.

Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Randomized Clinical Trials

“…On the other hand, ADCP involves the phagocytosis of cells by macrophages, which recognize the target cells by antibodies bound to the surface of the tumor cells; thus, this marking by Fc receptors leads to the destruction of these cells [60][61][62]. The combination of these mechanisms, ADC and ADCP, plays a crucial role in the efficacy of daratumumab and isatuximab, although the latter can also induce cell death by direct mechanisms that are independent of Fc [63][64][65].…”

Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies

“…Following binding, BM internalizes and releases MMAF, resulting in the disruption of the intracellular microtubule network, cell cycle arrest, and apoptosis. BM demonstrates potent antitumor activity through MMAF‐induced apoptosis, antibody‐dependent cytotoxicity, and antibody‐dependent cellular phagocytosis 195 . In 2020, it received FDA approval for the treatment of relapsed or refractory multiple myeloma 194 …”

“…BM demonstrates potent antitumor activity through MMAF-induced apoptosis, antibody-dependent cytotoxicity, and antibodydependent cellular phagocytosis. 195 In 2020, it received FDA approval for the treatment of relapsed or refractory multiple myeloma. 194 Furthermore, MT-ADCs have demonstrated promising results in the treatment of various solid tumors, including urothelial cancer, cervical cancer, breast cancer, and epithelial ovarian cancer.…”

Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells

“…The newly developed drugs such as immunomodulatory drugs (IMIDs), proteasome inhibitors (PIs), histone deacetylase inhibitors, and monoclonal antibody-based drugs have considerably improved the survival rates of patients with multiple myeloma (MM) [1]. Additionally, T cell-mediated therapies, such as stem cell transplantation and chimeric antigen receptor (CAR)-T cell or bispecific T cell engager (BiTE) therapy, have shown clinical potential, suggesting that myeloma cells are highly immunogenic [2][3][4]. However, myeloma is still an incurable disease, and most patients suffer from disease relapse after standard therapies [5].…”