Andersson Yvonne, Haavardtun Synne Ihler, Davidson Ben, Dørum Anne, Fleten Karianne G, Fodstad Øystein, Flatmark Kjersti
Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, 0310 Oslo, Norway.
Oncotarget. 2017 Jun 27;8(37):61800-61809. doi: 10.18632/oncotarget.18694. eCollection 2017 Sep 22.
Peritoneal metastasis (PM) is an important feature of epithelial ovarian cancer (EOC) and is a frequent site of drug resistant disease recurrence, identifying PM-EOC an important clinical challenge. The MOC31PE immunotoxin targets and kills tumor cells expressing the epithelial cell adhesion molecule (EpCAM), which is highly expressed in EOC, and MOC31PE is being investigated for use in treatment of PM-EOC. The efficacy of MOC31PE treatment alone and in combination with cytotoxic drugs was investigated in two human EpCAM expressing EOC cell lines, B76 and MDHA-2774, and in corresponding mouse models mimicking PM-EOC. MOC31PE efficaciously killed tumor cells alone and showed equal or superior activity (paclitaxel, cisplatin, carboplatin) and (paclitaxel, mitomycin C) compared to the investigated cytotoxic drugs. Additive, or importantly, no antagonistic effects were observed in combination experiments. In ex vivo cell culture, the cytotoxic effect of MOC31PE was studied on freshly isolated surgical EOC samples. All investigated fresh EOC samples expressed EpCAM and MOC31PE effectively reduced cell viability in ex vivo cultures. In conclusion, these results, together with our previous preclinical and clinical experience, support development of MOC31PE for treatment of PM-EOC in combination with currently used cytotoxic drugs.
腹膜转移（PM）是上皮性卵巢癌（EOC）的一个重要特征，是耐药疾病复发的常见部位，这使得PM-EOC成为一个重要的临床挑战。MOC31PE免疫毒素靶向并杀死表达上皮细胞粘附分子（EpCAM）的肿瘤细胞，EpCAM在EOC中高度表达，目前正在研究MOC31PE用于治疗PM-EOC。在两种表达人EpCAM的EOC细胞系B76和MDHA-2774以及模拟PM-EOC的相应小鼠模型中，研究了单独使用MOC31PE治疗以及与细胞毒性药物联合使用的疗效。MOC31PE单独使用时能有效杀死肿瘤细胞，与所研究的细胞毒性药物相比，其活性与（紫杉醇、顺铂、卡铂）相当或更优，与（紫杉醇、丝裂霉素C）相当或更优。在联合实验中观察到相加作用，重要的是，未观察到拮抗作用。在体外细胞培养中，研究了MOC31PE对新鲜分离的手术切除的EOC样本的细胞毒性作用。所有研究的新鲜EOC样本均表达EpCAM，MOC31PE在体外培养中有效降低了细胞活力。总之，这些结果与我们之前的临床前和临床经验一起，支持开发MOC31PE与目前使用的细胞毒性药物联合用于治疗PM-EOC。
