低亲和力神经生长因子受体
癌症研究
抗体
抗体依赖性细胞介导的细胞毒性
单克隆抗体
细胞培养
癌症
人源化抗体
医学
免疫学
生物
受体
内科学
神经营养素
遗传学
作者
Shinkichi Morita,Mai Mochizuki,Kouichi Wada,Rie Shibuya,Mao Nakamura,Kazunori Yamaguchi,Tomoko Yamazaki,Takayuki Imai,Yukinori Asada,Kazuto Matsuura,Kazuo Sugamura,Yukio Katori,Kennichi Satoh,Keiichi Tamai
标识
DOI:10.1016/j.canlet.2019.07.011
摘要
CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10−9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy.
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