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

作者：Nishii Yukari; Yamaguchi Miki; Kimura Yasutoshi; Hasegawa Tadashi; Aburatani Hiroyuki; Uchida Hiroaki; Hirata Koichi; Sakuma Yuji^*

来源：International Journal of Oncology, 2015, 46(4): 1781-1787.

DOI：10.3892/ijo.2015.2880

• pancreatic ductal carcinoma
• mucin 13
• monoclonal antibody
• antibody-drug conjugate
• internalization
• immunohistochemistry

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 Cl, 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.

• 出版日期2015-4