文章：

CD26是人源化单克隆抗体治疗多发性骨髓瘤的潜在治疗靶点

CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma

原文发布日期：2018-10-22

DOI: 10.1038/s41408-018-0127-y

类型: Article

开放获取: 是

英文摘要：

CD26, a 110-kDa transmembrane glycoprotein that is expressed on several tumor cells including malignant lymphoma, has been implicated in tumorigenesis: however, little is known regarding its role in multiple myeloma (MM). Recently, we identified CD26 expression on human osteoclasts (OCs) and demonstrated that humanized IgG1 monoclonal antibody targeting CD26, huCD26mAb, inhibits human OC differentiation. Herein, we show that CD26 expression was present on plasma cells in the bone marrow tissues of MM patients. In vitro immunostaining studies revealed that although CD26 expression was low or absent on MM cell lines cultured alone, it was intensely and uniformly expressed on MM cell lines co-cultured with OCs. The augmented CD26 expression in MM cells was exploited to enhance anti-MM efficacy of huCD26mAb via a substantial increase in antibody-dependent cytotoxicity (ADCC) but not complement-dependent cytotoxicity (CDC). Moreover, huCD26mAb in combination with novel agents synergistically enhanced huCD26mAb induced ADCC activity against CD26+ MM cells compared with each agent alone. huCD26mAb additionally reduced the ratio of the side population (SP) fraction in CD26+ MM cells by ADCC. Finally, huCD26mAb significantly reduced the MM tumor burden and OC formation in vivo. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent.

摘要翻译： 

CD26是一种表达于多种肿瘤细胞（包括恶性淋巴瘤）的110kDa跨膜糖蛋白，与肿瘤发生密切相关，但对其在多发性骨髓瘤（MM）中的作用知之甚少。近期我们在人类破骨细胞（OCs）中发现CD26表达，并证实靶向CD26的人源化IgG1单克隆抗体huCD26mAb可抑制人类破骨细胞分化。本文中，我们发现在多发性骨髓瘤患者骨髓组织的浆细胞中存在CD26表达。体外免疫染色研究显示，虽然单独培养的多发性骨髓瘤细胞系中CD26表达量较低或缺失，但在与破骨细胞共培养的多发性骨髓瘤细胞系中CD26呈现强烈而均匀的表达。通过显著增强抗体依赖性细胞毒性（ADCC）而非补体依赖性细胞毒性（CDC），我们利用多发性骨髓瘤细胞中增强的CD26表达来提高huCD26mAb的抗骨髓瘤疗效。此外，与单一用药相比，huCD26mAb联合新型药物能协同增强其对CD26阳性多发性骨髓瘤细胞诱导的ADCC活性。huCD26mAb还通过ADCC作用降低了CD26阳性多发性骨髓瘤细胞中侧群细胞（SP）的比例。最终，huCD26mAb在体内显著降低了多发性骨髓瘤肿瘤负荷和破骨细胞形成。这些结果表明CD26是多发性骨髓瘤的潜在靶点分子，而huCD26mAb可能成为一种治疗药物。

原文链接：

CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma