Kato Yukinari, Kunita Akiko, Fukayama Masashi, Abe Shinji, Nishioka Yasuhiko, Uchida Hiroaki, Tahara Hideaki, Yamada Shinji, Yanaka Miyuki, Nakamura Takuro, Saidoh Noriko, Yoshida Kanae, Fujii Yuki, Honma Ryusuke, Takagi Michiaki, Ogasawara Satoshi, Murata Takeshi, Kaneko Mika K
1 Tohoku University Graduate School of Medicine , Sendai, Japan .
2 Department of Pathology, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan .
Monoclon Antib Immunodiagn Immunother. 2017 Feb;36(1):20-24. doi: 10.1089/mab.2016.0045.
The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.
血小板源性生长因子（PDPN）与C型凝集素样受体2（CLEC-2）之间的相互作用与肿瘤恶性程度有关。我们利用癌症特异性单克隆抗体（CasMab）技术制备了许多抗人血小板源性生长因子的单克隆抗体（mAb）。LpMab-21是一种小鼠抗血小板源性生长因子单克隆抗体，属于IgG亚类，其最小表位被确定为人血小板源性生长因子的Thr76-Arg79。重要的是，唾液酸与Thr76相连；因此，LpMab-21是一种抗糖肽单克隆抗体（GpMab）。在本研究中，我们研究了LpMab-21在体外是否对表达人血小板源性生长因子的癌细胞系表现出抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC），并使用异种移植模型研究了其抗肿瘤活性。LpMab-21不仅对表达血小板源性生长因子的中国仓鼠卵巢细胞，而且对内源性表达血小板源性生长因子的LN319胶质母细胞瘤细胞和PC-10肺癌细胞均表现出高ADCC和CDC活性。此外，LpMab-21在体内可抑制肿瘤生长，这表明LpMab-21可用于针对表达人血小板源性生长因子的癌症的抗体治疗。
