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, in vitro and in corresponding mouse models mimicking PM-EOC. MOC31PE efficaciously killed
tumor cells alone and showed equal or superior activity in vitro (
paclitaxel, cisplatin,
carboplatin) and in vivo (
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.