Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1, Medeshima-Shiode, Natori, Miyagi, Japan; Department of Head and Neck Surgery, Miyagi Cancer Center, 47-1, Medeshima-Shiode, Natori, Miyagi, Japan.
Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1, Medeshima-Shiode, Natori, Miyagi, Japan.
Cancer Lett. 2019 Oct 1;461:144-152. doi: 10.1016/j.canlet.2019.07.011. Epub 2019 Jul 17.
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 (K = 1.697 × 10 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.
CD271，又称为神经营养因子受体，在多种癌症中表达，如下咽癌（HPC）和黑色素瘤。我们最近报道称，CD271 是 HPC 的癌症干细胞标志物，其表达对于癌细胞增殖是必需的，并且与该疾病的不良预后相关。在这里，为了开发针对 CD271 的治疗性抗体，我们建立了一种人源化抗 CD271 单克隆抗体（hCD271 mAb）。hCD271 mAb 与人 CD271 的富含半胱氨酸结构域 1（CRD1）具有高亲和力（K=1.697×10-7 M）。在体外，hCD271 mAb 对 SP2/0-CD271（人 CD271 转导的小鼠细胞系）发挥抗体依赖的细胞介导的细胞毒性（ADCC）活性。hCD271 mAb 的治疗还在三种细胞系（HPCM2（下咽癌患者来源的异种移植细胞系）、MeWo-Luc（黑色素瘤细胞系）和 SP2/0-CD271）的移植模型中发挥了抗肿瘤活性，与对照组相比，肿瘤更小，CD271 阳性细胞数量减少。总之，这些数据表明靶向 CD271 的抗体是一种很有前途的治疗策略。
