Itai Shunsuke, Yamada Shinji, Kaneko Mika K, Harada Hiroyuki, Kagawa Yumiko, Konnai Satoru, Kato Yukinari
1 Department of Antibody Drug Development, Tohoku University Graduate School of Medicine , Sendai, Miyagi, Japan .
2 Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
Monoclon Antib Immunodiagn Immunother. 2017 Dec;36(6):243-250. doi: 10.1089/mab.2017.0046. Epub 2017 Nov 1.
Oral squamous cell carcinoma is an aggressive tumor in cats; however, molecular-targeted therapies against this tumor, including antibody therapy, have not been developed. Sensitive and specific monoclonal antibodies (mAbs) against highly expressed membrane proteins are needed to develop antibody therapies. Podoplanin, a type I transmembrane glycoprotein, is expressed in many human malignant tumors, including brain tumor, esophageal cancer, lung cancer, mesothelioma, and oral cancer. Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) and activates platelet aggregation, which is involved in cancer metastasis. Until now, we have established several mAbs against podoplanin in humans, mice, rats, rabbits, dogs, cattle, and cats. We have reported podoplanin expression in canine melanoma and squamous cell carcinomas using an anti-dog podoplanin mAb PMab-38. In this study, we investigated podoplanin expression in 40 feline squamous cell carcinomas (14 cases of mouth floor, 13 of skin, 9 of ear, and 4 of tongue) by immunohistochemical analysis using an anti-cat podoplanin mAb PMab-52, which we recently developed by cell-based immunization and screening (CBIS) method. Of the total 40 cases, 38 (95%) showed positive staining for PMab-52. In particular, 12 cases (30%) showed a strong membrane-staining pattern of squamous cell carcinoma cells. PMab-52 can be useful for antibody therapy against feline podoplanin-expressing squamous cell carcinomas.
口腔鳞状细胞癌是猫的一种侵袭性肿瘤；然而，针对这种肿瘤的分子靶向疗法，包括抗体疗法，尚未得到开发。开发抗体疗法需要针对高表达膜蛋白的敏感且特异的单克隆抗体（mAb）。血小板反应蛋白-1，一种I型跨膜糖蛋白，在许多人类恶性肿瘤中表达，包括脑肿瘤、食管癌、肺癌、间皮瘤和口腔癌。血小板反应蛋白-1与C型凝集素样受体-2（CLEC-2）结合并激活血小板聚集，这与癌症转移有关。到目前为止，我们已经在人、小鼠、大鼠、兔子、狗、牛和猫身上建立了几种针对血小板反应蛋白-1的单克隆抗体。我们已经使用抗犬血小板反应蛋白-1单克隆抗体PMab-38报道了血小板反应蛋白-1在犬黑色素瘤和鳞状细胞癌中的表达。在本研究中，我们使用抗猫血小板反应蛋白-1单克隆抗体PMab-52通过免疫组织化学分析研究了40例猫鳞状细胞癌（14例口底、13例皮肤、9例耳部和4例舌部）中血小板反应蛋白-1的表达，该抗体是我们最近通过基于细胞的免疫和筛选（CBIS）方法开发的。在总共40例病例中，38例（95%）对PMab-52呈阳性染色。特别是，12例（30%）显示鳞状细胞癌细胞有强烈的膜染色模式。PMab-52可用于针对表达猫血小板反应蛋白-1的鳞状细胞癌的抗体治疗。
