A newly developed anti-Mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells

Nishii,Yukari; Yamaguchi,Miki; Kimura,Yasutoshi; Hasegawa,Tadashi; Aburatani,Hiroyuki; Uchida,Hiroaki; Hirata,Koichi; Sakuma,Yuji

doi:10.3892/ijo.2015.2880

A newly developed anti-Mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells

Authors:
- Yukari Nishii
- Miki Yamaguchi
- Yasutoshi Kimura
- Tadashi Hasegawa
- Hiroyuki Aburatani
- Hiroaki Uchida
- Koichi Hirata
- Yuji Sakuma
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Affiliations: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan, Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan, Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan, Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
Published online on: February 5, 2015 https://doi.org/10.3892/ijo.2015.2880
Pages: 1781-1787

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Abstract

Pancreatic cancer is one of the most severe forms of malignancy. Patients with unresectable or metastatic pancreatic cancer usually receive chemotherapy that causes various adverse effects. Antibody-drug conjugates (ADCs), drugs developed by conjugating an anticancer agent to a monoclonal antibody (mAb), can alleviate the side effects of chemotherapy because ADCs selectively bind to cancer cells expressing a particular antigen. We recently developed the recombinant protein DT3C comprising diphtheria toxin (DT) lacking the receptor-binding domain but containing the C1, C2, and C3 domains of Streptococcus protein G (3C). The mAb-DT3C conjugates can be used to select mAbs that are internalized by cells, because the conjugates decrease cell viability only when they are internalized by cells through Ab-antigen reactions. We developed a new mAb to be internalized by TCC-PAN2 cells, a pancreatic carcinoma cell line. The mAb, designated TCC56, recognized Mucin 13 (MUC13), while TCC56‑DT3C conjugates induced cell death in TCC-PAN2 cells expressing MUC13. We found that MUC13 was expressed, at least partially, in all 40 pancreatic ductal carcinoma tissues and adjacent non-cancerous tissues analyzed. The expression levels of MUC13 in pancreatic cancer tissues were greater than those in normal tissues. Our findings suggest that MUC13 can be a target molecule for pancreatic cancer treatment. ADCs, including mAb TCC56, could be promising anticancer agents to alleviate the adverse effects of chemotherapy.

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