我院魏海明教授和田志剛教授研究組發(fā)現(xiàn)白血病新型治療靶標(biāo)。近年來，腫瘤靶向抗體治療成為生物藥物研發(fā)的熱點(diǎn)，而這其中尋找和開發(fā)新靶點(diǎn)尤為關(guān)鍵。髓系白血病是我國高發(fā)的白血病亞型，目前臨床依然缺乏有效治療手段。該研究組通過比較急性髓系白血病細(xì)胞和正常骨髓細(xì)胞基因表達(dá)譜，發(fā)現(xiàn)EpCAM在急性髓系白血病病人骨髓細(xì)胞中高表達(dá)，EpCAM陽性白血病細(xì)胞致癌性和化療抵抗性明顯增強(qiáng)，成為一種髓系白血病新型治療靶點(diǎn)，該課題組自主研發(fā)的抗EpCAM抗體能夠激活巨噬細(xì)胞和自然殺傷細(xì)胞，發(fā)揮抗白血病效應(yīng)。該項(xiàng)研究成果以“EpCAM inhibition sensitizes chemoresistant leukemia to immune surveillance”為題在線發(fā)表于Cancer Research雜志（DOI: 10.1158/0008-5472. CAN-16-0842 Published 3 October 2016），鄭小虎博士后為本文第一作者。
作者：Xiaohu Zheng, Xiaolei Fan, Binqing Fu, Meijuan Zheng, Aimei Zhang, Kai Zhong, Jialai Yan, Rui Sun, Zhigang Tian*, Haiming Wei*
摘要：The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling. Furthermore, we generated EpCAM antibodies that enabled phagocytosis or cytotoxicity of AML cells by macrophage or natural killer (NK) cells, respectively. Finally, EpCAM antibody treatment depleted AML in subcutaneous, disseminated, and intramedullary engrafted mice. In summary, EpCAM exhibits promise as a novel target for the treatment of leukemia.
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