Open AccessAntitumor activity of chLpMab‐2, a human–mouse chimeric cancer‐specific antihuman podoplanin antibody, via antibody‐dependent cellular cytotoxicity
Author(s) -
Kaneko Mika K.,
Yamada Shinji,
Nakamura Takuro,
Abe Shinji,
Nishioka Yasuhiko,
Kunita Akiko,
Fukayama Masashi,
Fujii Yuki,
Ogasawara Satoshi,
Kato Yukinari
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1049
Subject(s) - podoplanin , antibody dependent cell mediated cytotoxicity , monoclonal antibody , chinese hamster ovary cell , cytotoxicity , cancer research , antibody , chemistry , flow cytometry , microbiology and biotechnology , biology , immunology , receptor , in vitro , lymphatic system , biochemistry
Human podoplanin (h PDPN ), 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 h PDPN is involved in invasion and metastasis. Anti‐h PDPN monoclonal antibodies (mAbs) such as NZ ‐1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation‐stimulating ( PLAG ) domain of h PDPN . Recently, we developed a novel mouse anti‐h PDPN mAb, LpMab‐2, using the cancer‐specific mAb (CasMab) technology. In this study we developed chLpMab‐2, a human–mouse chimeric anti‐h PDPN 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 h PDPN ‐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 /h PDPN , indicating that chLpMab‐2 suppressed tumor development via ADCC . In conclusion, chLpMab‐2 could be useful as a novel antibody‐based therapy against h PDPN ‐expressing tumors.