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

// Tatsuzo Mizukami 1 , Hirofumi Kamachi 1 , Yuki Fujii 1 , Fumihiko Matsuzawa 1 , Takahiro Einama 1 , Futoshi Kawamata 1 , Nozomi Kobayashi 1 , Yutaka Hatanaka 2 and Akinobu Taketomi 1 1 Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan 2 Research division of Companion Diagnostics, Hokkaido University Hospital, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan Correspondence to: Hirofumi Kamachi, email: hkamachi@db3.so-net.ne.jp Keywords: amatuximab; mesothelin; pancreatic cancer; peritoneal metastasis; adjuvant chemotherapy Received: February 26, 2018 Accepted: September 01, 2018 Published: September 18, 2018 ABSTRACT 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.