Therapeutic monoclonal antibodies for multiple myeloma: an update and future perspectives

Multiple myeloma (MM) still remains incurable in most of the patients. Despite of treatments with high-dose chemotherapy, stem cell transplantation and other novel therapies, most patients will become refractory to the therapies and relapse. Thus, it is urgent to develop new approaches for MM treatment. Currently, antibody-targeted therapy has been extensively utilized in hematological malignancies, including MM. Several novel monoclonal antibodies (mAbs) against MM have been generated and developed over the past several years. These mAbs aim to target not only tumor cells alone but also tumor microenvironment, including interaction of tumor-bone marrow stromal cells and the components of bone marrow milieu, such as cytokines or chemokines that support myeloma cell growth and survival. These include mAbs specific for CD38, CS1, CD40, CD74, CD70, HM1.24, interleukin-6 and β(2)-microglobulin (β(2)M). We have shown that anti-β(2)M mAbs may be a potential antitumor agent for MM therapy due to their remarkable efficacy to induce myeloma cell apoptosis in tumor cell lines and primary myeloma cells from patients in vitro and in established myeloma mouse models. In this article, we will review advances in the development and mechanisms of MM-targeted mAbs and especially, anti-β(2)M mAbs. We will also discuss the potential application of the mAbs as therapeutic agents to treat MM.