Abstract
Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the “don’t eat me” signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 “don’t eat me” signal is a novel and promising strategy for the treatment of MM, providing a basis for additional studies to validate these effects in vivo and in patients.
Highlights
Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematologic malignancy in the world [1]
We hypothesized that blocking CD47 on MM cells with monoclonal antibodies (mAbs) will enhance phagocytosis and killing of MM, which represents a novel strategy for MM
The aim of this study is to investigate the effect of a new anti-CD47 antibody Vx1000R on will enhance phagocytosis and killing of MM, which represents a novel strategy for MM cancer inducing phagocytosis and killing of MM cells
Summary
Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematologic malignancy in the world [1]. Therapeutic breakthroughs such as proteasome inhibitor (PIs), immunomodulatory drugs (IMiDs), and antibody-based therapeutics have substantially expanded the number of treatment regimens available for patients in all stages of MM [2]. Cancers 2020, 12, 305 patients eventually relapse or become refractory to treatment, which lowers the median survival to only. New approaches are needed to effectively target and eliminate MM. Cancer immunotherapy has gained heightened attention as a promising approach for treatment of MM and relapse/refractory MM, since many tumor-associated antigens have been identified in MM cells [4]. Immunotherapies focus on the repair, stimulation, and/or enhancement of the body’s natural immune responses to fight cancer. The recovery of immune surveillance can block tumor development with fewer adverse effects, which can serve as a powerful tool for long-term control of MM
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