title: Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.
abstract: 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 IgG2asubclass, 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.
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.affiliation: 2 Department of Pathology, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan .
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.affiliation: 2 Department of Pathology, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan .
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: 3 Department of Clinical Pharmacy Practice Pedagogy, Graduate School of Biomedical Sciences, Tokushima University , Tokushima, Japan .|4 Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University , Tokushima, Japan .
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.affiliation: 4 Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University , Tokushima, Japan .
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.affiliation: 5 Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan .
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Uchida
authors.affiliation: 5 Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan .
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tahara
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamada
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yanaka
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Takuro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Noriko
authors.initials: N
authors.lastname: Saidoh
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Kanae
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .|6 Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine , Yamagata, Japan .
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Honma
authors.affiliation: 6 Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine , Yamagata, Japan .
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .|7 Department of Chemistry, Graduate School of Science, Chiba University , Chiba, Japan .|8 Molecular Chirality Research Center, Chiba University , Chiba, Japan .
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.affiliation: 7 Department of Chemistry, Graduate School of Science, Chiba University , Chiba, Japan .|8 Molecular Chirality Research Center, Chiba University , Chiba, Japan .
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.affiliation: 1 Tohoku University Graduate School of Medicine , Sendai, Japan .
authors.forename: Mika K
authors.initials: MK
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D016466:CHO Cells; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology*; D003412:Cricetulus; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006020:Glycopeptides / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000098853:Podoplanin
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003165:Complement System Proteins; D006020:Glycopeptides; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D019158:N-Acetylneuraminic Acid; C104778:CLEC2B protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: ADCC; CDC; antitumor activity; monoclonal antibody; podoplanin