Hayashi Toshiaki, Treon Steven P, Hideshima Teru, Tai Yu-Tzu, Akiyama Masaharu, Richardson Paul, Chauhan Dharminder, Grewal Iqbal S, Anderson Kenneth C
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Br J Haematol. 2003 May;121(4):592-6. doi: 10.1046/j.1365-2141.2003.04322.x.
Multiple myeloma (MM) is currently incurable, and novel therapies are needed. In this study, we examined a novel recombinant humanized monoclonal antibody against CD40 (rhuCD40 mAb) and demonstrate for the first time that rhuCD40 mAb induces antibody-dependent cell-mediated cytotoxicity (ADCC) against CD40-positive MM cells. Importantly, we show that rhuCD40 mAb induces autologous ADCC against primary patient MM cells, without triggering ADCC against normal B cells. This study, therefore, both demonstrates that rhuCD40 mAb triggers autologous ADCC against patient MM cells and provides the framework for the clinical evaluation of rhuCD40 mAb immunotherapy to improve patient outcome in MM.
多发性骨髓瘤(MM)目前无法治愈,因此需要新的治疗方法。在本研究中,我们检测了一种新型抗CD40重组人源化单克隆抗体(rhuCD40 mAb),并首次证明rhuCD40 mAb可诱导针对CD40阳性MM细胞的抗体依赖性细胞介导的细胞毒性(ADCC)。重要的是,我们发现rhuCD40 mAb可诱导针对原发性患者MM细胞的自体ADCC,而不会触发针对正常B细胞的ADCC。因此,本研究既证明了rhuCD40 mAb可触发针对患者MM细胞的自体ADCC,也为rhuCD40 mAb免疫疗法的临床评估提供了框架,以改善MM患者的预后。