我院魏海明教授和田志刚教授研究组发现白血病新型治疗靶标。近年来，肿瘤靶向抗体治疗成为生物药物研发的热点，而这其中寻找和开发新靶点尤为关键。髓系白血病是我国高发的白血病亚型，目前临床依然缺乏有效治疗手段。该研究组通过比较急性髓系白血病细胞和正常骨髓细胞基因表达谱，发现EpCAM在急性髓系白血病病人骨髓细胞中高表达，EpCAM阳性白血病细胞致癌性和化疗抵抗性明显增强，成为一种髓系白血病新型治疗靶点，该课题组自主研发的抗EpCAM抗体能够激活巨噬细胞和自然杀伤细胞，发挥抗白血病效应。该项研究成果以“EpCAM inhibition sensitizes chemoresistant leukemia to immune surveillance”为题在线发表于Cancer Research杂志（DOI: 10.1158/0008-5472. CAN-16-0842 Published 3 October 2016），郑小虎博士后为本文第一作者。
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.
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.