title: A newly developed anti-Mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells.
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.
authors: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yukari
authors: Y
authors: Nishii
authors: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Miki
authors: M
authors: Yamaguchi
authors: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yasutoshi
authors: Y
authors: Kimura
authors: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Tadashi
authors: T
authors: Hasegawa
authors: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Aburatani
authors: Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors: Hiroaki
authors: H
authors: Uchida
authors: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Koichi
authors: K
authors: Hirata
authors: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yuji
authors: Y
authors: Sakuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008875:Middle Aged; D009077:Mucins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; C429552:MUC13 protein, human; D009077:Mucins