%0 Journal Article
%T Antitumor activity of chLpMab©\2, a human¨Cmouse chimeric cancer©\specific antihuman podoplanin antibody, via antibody©\dependent cellular cytotoxicity
%A Akiko Kunita
%A Masashi Fukayama
%A Mika K. Kaneko
%A Satoshi Ogasawara
%A Shinji Abe
%A Shinji Yamada
%A Takuro Nakamura
%A Yasuhiko Nishioka
%A Yuki Fujii
%A Yukinari Kato
%J Archive of "Cancer Medicine".
%D 2017
%R 10.1002/cam4.1049
%X Human podoplanin (hPDPN), a platelet aggregation©\inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C©\type lectin©\like receptor 2 (CLEC©\2). The overexpression of hPDPN is involved in invasion and metastasis. Anti©\hPDPN monoclonal antibodies (mAbs) such as NZ©\1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation©\stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti©\hPDPN mAb, LpMab©\2, using the cancer©\specific mAb (CasMab) technology. In this study we developed chLpMab©\2, a human¨Cmouse chimeric anti©\hPDPN antibody, derived from LpMab©\2. chLpMab©\2 was produced using fucosyltransferase 8©\knockout (KO) Chinese hamster ovary (CHO)©\S cell lines. By flow cytometry, chLpMab©\2 reacted with hPDPN©\expressing cancer cell lines including glioblastomas, mesotheliomas, and lung cancers. However, it showed low reaction with normal cell lines such as lymphatic endothelial and renal epithelial cells. Moreover, chLpMab©\2 exhibited high antibody©\dependent cellular cytotoxicity (ADCC) against PDPN©\expressing cells, despite its low complement©\dependent cytotoxicity. Furthermore, treatment with chLpMab©\2 abolished tumor growth in xenograft models of CHO/hPDPN, indicating that chLpMab©\2 suppressed tumor development via ADCC. In conclusion, chLpMab©\2 could be useful as a novel antibody©\based therapy against hPDPN©\expressing tumors
%K Antibody©\dependent cellular cytotoxicity
%K chimeric antibody
%K human podoplanin
%K monoclonal antibody
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387135/