The anti-mesothelin monoclonal antibody amatuximab enhances the anti-tumor effect of gemcitabine against mesothelin-high expressing pancreatic cancer cells in a peritoneal metastasis mouse model
| Autor: | Tatsuzo Mizukami, Nozomi Kobayashi, Yuki Fujii, Fumihiko Matsuzawa, Futoshi Kawamata, Hirofumi Kamachi, Takahiro Einama, Akinobu Taketomi, Yutaka Hatanaka |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system diseases Combination therapy medicine.drug_class pancreatic cancer Amatuximab Monoclonal antibody 03 medical and health sciences 0302 clinical medicine Pancreatic cancer medicine Adjuvant therapy Mesothelin amatuximab biology business.industry Cancer mesothelin medicine.disease Gemcitabine adjuvant chemotherapy 030104 developmental biology Oncology peritoneal metastasis 030220 oncology & carcinogenesis Cancer research biology.protein business Research Paper medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.26117 |
| Popis: | Pancreatic cancer often has a very poor prognosis, even after complete resection. The recurrence of hepatic and peritoneal metastases is an important prognostic factor; therefore, the development of improved adjuvant therapy is urgently required. Mesothelin is a cell surface glycoprotein whose expression is restricted to a variety of cancer types, including pancreatic cancer. This expression pattern makes mesothelin an attractive target for cancer therapy, and several agents targeting mesothelin are currently in clinical trials. Here, we used the chimerized high-affinity anti-mesothelin monoclonal antibody amatuximab to investigate its effect on peritoneal metastasis. We used the AsPC-1 pancreatic cancer cell line engineered to express Gaussia luciferase (Gluc), (AsPC-1-Gluc) for in vivo experiments. Results showed that while amatuximab was not directly cytotoxic on an AsPC-1-Gluc tumor cells in a peritoneal metastasis model, it prevented the formation of tumor growth. In combination therapy with gemcitabine, amatuximab exhibited synergistic killing. Our results suggest that blockade of mesothelin by amatuximab may be a useful strategy for preventing the peritoneal dissemination of pancreatic cancer under an adjuvant setting. |
| Databáze: | OpenAIRE |
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