A newly developed anti-Mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells
A newly developed anti-Mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells
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DOI：
10.3892/ijo.2015.2880
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发表时间：
2015-04-01
影响因子：
5.2
通讯作者：
Sakuma, Yuji
中科院分区：
文献类型：
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作者：
Nishii, Yukari;Yamaguchi, Miki;Sakuma, Yuji
胰腺癌是最严重的恶性肿瘤之一。不可切除或转移性胰腺癌患者通常接受化疗，化疗会引起各种不良反应。抗体-药物偶联物（adc）是通过将抗癌剂与单克隆抗体（mAb）偶联而开发的药物，由于adc选择性地与表达特定抗原的癌细胞结合，可以减轻化疗的副作用。我们最近开发了重组蛋白DT3C，其中白喉毒素（DT）缺乏受体结合结构域，但含有链球菌蛋白G （3C）的Cl， C2和C3结构域。单克隆抗体- dt3c偶联物可用于选择被细胞内化的单克隆抗体，因为这些偶联物只有在通过抗体抗原反应被细胞内化时才会降低细胞活力。我们开发了一种新的单抗，可以被胰腺癌细胞系TCC-PAN2细胞内化。命名为TCC56的单抗识别Mucin 13 (MUC13)，而TCC56- dt3c偶联物在表达MUC13的TCC-PAN2细胞中诱导细胞死亡。我们发现MUC13在所有40例胰导管癌组织和邻近非癌组织中至少部分表达。MUC13在胰腺癌组织中的表达水平高于正常组织。我们的研究结果表明MUC13可以成为胰腺癌治疗的靶分子。adc，包括单抗TCC56，可能是有希望的抗癌药物，以减轻化疗的不良反应。
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.