モノクローナル抗体による多発性骨髄腫の免疫療法

Multiple myeloma is so far an incurable malignancy because of marked resistance of tumor cell to conventional chemotherapeutic agents even if myeloablative treatment has been applied with hematopoietic stem cell transplantation. The challenge remains to develop less toxic, but more effective, targeted therapies. We have generated a monoclonal antibody (mAb), which detects a human plasma cell specific antigen, HM 1.24, to develop a new immunotherapy for multiple myeloma. This mAb has been shown to inhibit the proliferation of human myeloma cells implanted into severe combined immunodeficiency mice by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC). Subsequently, for the clinical application to treatment of myeloma patients, the murine mAb was humanized through genetic engineering methods to ameliorate the host humoral response and to mediate ADCC against myeloma cells in the presence of human effector cells, CD 16+ NK cells. Using the humanized anti-HM 1.24 mAb, but not the murine mAb, the peripheral blood mononuclear cells (PBMCs) from myeloma patients exhibited ADCC activity as efficiently as those of healthy donors. These results promise that humanized anti-HM 1.24 has potential as a new therapeutic strategy in refractory multiple myeloma.