Anti-beta M-2 monoclonal antibodies kill myeloma cells via cell- and complement-mediated cytotoxicity

作者：Zhang Mingjun; Qian Jianfei; Lan Yongsheng; Lu Yong; Li Haiyan; Hong Bangxing; Zheng Yuhuan; He Jin; Yang Jing; Yi Qing^*

来源：International Journal of Cancer, 2014, 135(5): 1132-1141.

DOI：10.1002/ijc.28745

• beta(2)-microglubulin
• monoclonal antibody
• antibody-dependent cell-mediated cytotoxicity
• complement-dependent cytotoxicity
• multiple myeloma

Our previous studies showed that anti-beta M-2 monoclonal antibodies (mAbs) at high doses have direct apoptotic effects on myeloma cells, suggesting that anti-beta M-2 mAbs might be developed as a novel therapeutic agent. In this study, we investigated the ability of the mAbs at much lower concentrations to indirectly kill myeloma cells by utilizing immune effector cells or molecules. Our results showed that anti-beta M-2 mAbs effectively lysed MM cells via antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which were correlated with and dependent on the surface expression of beta M-2 on MM cells. The presence of MM bone marrow stromal cells or addition of IL-6 did not attenuate anti-beta M-2 mAb-induced ADCC and CDC activities against MM cells. Furthermore, anti-beta M-2 mAbs only showed limited cytotoxicity toward normal B cells and nontumorous mesenchymal stem cells, indicating that the ADCC and CDC activities of the anti-beta M-2 mAbs were more prone to the tumor cells. Lenalidomide potentiated in vitro ADCC activity against MM cells and in vivo tumor inhibition capacity induced by the anti-beta M-2 mAbs by enhancing the activity of NK cells. These results support clinical development of anti-beta M-2 mAbs, both as a monotherapy and in combination with lenalidomide, to improve MM patient outcome.

• 出版日期2014-9-1