MOC31PE immunotoxin – targeting peritoneal metastasis from epithelial ovarian cancer
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Yvonne Andersson1, Synne Ihler Haavardtun1,5, Ben Davidson2,5, Anne Dørum3, Karianne G. Fleten1,5, Øystein Fodstad1,5 and Kjersti Flatmark1,4,5
1Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, Norway
2Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, Norway
3Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, Norway
4Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, Norway
5Institute of Clinical Medicine, University of Oslo, 0310 Oslo, Norway
Yvonne Andersson, email: [email protected]
Keywords: MOC31PE immunotoxin, EpCAM, peritoneal metastasis of epithelial ovarian cancer, chemotherapy, animal models
Received: December 06, 2016 Accepted: May 15, 2017 Published: June 27, 2017
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.
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