Multiple myeloma (MM) is a plasma cell neoplasm, characterized as malignant plasma cell infiltrating and growing in the bone marrow (BM) and development of a progressive osteolytic bone disease [1
]. This disease is one of the most common hematological malignancies among people older than 65 years in the United States and is more prevalent than lymphocytic leukemia, myelocytic leukemia or Hodgkin disease [2
]. Estimated by the American Cancer Society, approximately 20,580 new cases were diagnosed and about 10,580 patients died from this disease in 2009 [3
]. Although advances in the treatment of MM by new therapeutic agents, such as thalidomide, lenalidomide, and the proteasome inhibitor bortezomib, has been reported to prolong patient survival to 5-7 years over the past decades [4
], this disease still remains a largely incurable and fetal, and patients are prone to quickly relapse after high-dose chemotherapy, stem cell transplantation and other novel therapies [4
]. Therefore, development of a novel therapeutic approach to eradicate tumor cells is necessary, and will be helpful to improve overcomes of patients with MM.
Application of monoclonal antibodies (mAbs) is one of the successful approaches and has been utilized in current cancer therapy. Although the mechanism of mAb action to initiate and induce tumor cell death is not entirely known so far, it has been proposed that mAbs are able to bind to and cross-link target molecules and subsequently, elicit antibody-dependent cell-mediated cytotoxicity (ADCC) and activate complement-dependent cytotoxicity (CDC), and/or directly induce tumor cell apoptosis [5
]. For induction of mAb-mediated ADCC, binding of the Fc portion of mAbs to Fcγ receptors on immune cells is necessary. The immune cells including monocytes, natural killer cells, and granulocytes can destruct mAb-bound tumor cells either by phagocytosis or by release of cytotoxic granules contained in immune effector cells. To induce antibody-mediated CDC, cross-linking of mAbs activates complement cascades, which trigger assembly of membrane attack complex and subsequently, osmotic cell lysis. Moreover, a few of mAbs can directly induce tumor cell apoptosis through transduction of an apoptotic signal to cells, which triggers intracellular apoptotic signaling pathways and cleaves caspase and poly (ADP-ri-bose) polymerase (PARP), leading to tumor cell apoptosis [5
Thus far, several mAbs have been successfully used in solid tumors, such as trastuzumab for breast cancer [6
]; bevacizumab for renal cell carcinoma and colorectal cancer [7
] and cetuximab for squamous-cell carcinoma of the head and neck [9
]. Because therapeutic efficacy of mAbs can be achieved at low doses and response can be achieved rapidly, mAbs also have been extensively used in hematological malignances. One successful example is rituximab, a chimeric human-mouse mAb specific for CD20, a cell surface glycoprotein expressed on the majority of B cells. This mAb so far has been used as a frontline therapy for diffuse large B-cell lymphoma and other B-cell tumors [11
], even though its therapeutic efficacy may vary in individual patients. Derived from rituximab, several novel anti-CD20 mAbs have been developed, such as ofatumumab, ocrelizumab, veltuzumab, GA101, AME-133v and PRO131921 [5
]. The potential of their therapeutic efficacy is currently under investigation in preclinical and early clinical studies. Unfortunately, the majority of myeloma patients are not sensitive to anti-CD20 mAb treatment, because only 20% of malignant plasma cells from patients with MM express CD20 [15
]. To develop specific and potential therapeutic mAbs for MM, several novel mAbs have been generated recently. In this review, we will focus on mAbs that have been developed in the past years and may become potential therapeutic agents in MM in the near future.