Anti‐β2M monoclonal antibodies kill myeloma cells via cell‐ and complement‐mediated cytotoxicity. Issue 5 (7th February 2014)

• Record Type: Journal Article
• Authors: Zhang, Mingjun; Qian, Jianfei; Lan, Yongsheng; Lu, Yong; Li, Haiyan; Hong, Bangxing; Zheng, Yuhuan; He, Jin; Yang, Jing; Yi, Qing
• Is Part Of: International journal of cancer. Volume 135:Issue 5(2014:Sep. 01)
• Page Start: 1132
• Page End: 1141
• Publication Date: 2014-02-07
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28745
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Our previous studies showed that anti‐β<sub>2</sub>M monoclonal antibodies (mAbs) at high doses have direct apoptotic effects on myeloma cells, suggesting that anti‐β<sub>2</sub>M 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‐β<sub>2</sub>M mAbs effectively lysed MM cells <italic>via</italic> antibody‐dependent cell‐mediated cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC), which were correlated with and dependent on the surface expression of β<sub>2</sub>M on MM cells. The presence of MM bone marrow stromal cells or addition of IL‐6 did not attenuate anti‐β<sub>2</sub>M mAb‐induced ADCC and CDC activities against MM cells. Furthermore, anti‐β<sub>2</sub>M mAbs only showed limited cytotoxicity toward normal B cells and nontumorous mesenchymal stem cells, indicating that the ADCC and CDC activities of the anti‐β<sub>2</sub>M mAbs were more prone to the tumor cells. Lenalidomide potentiated <italic>in vitro</italic> ADCC activity against MM cells and <italic>in vivo</italic> tumor inhibition capacity induced by the anti‐β<sub>2</sub>M mAbs by enhancing the activity of NK cells. These results support clinical development of anti‐β<sub>2</sub>M mAbs, both as a monotherapy and in combination with lenalidomide, to improve MM patient outcome.</p> </abstract>