title: Chimeric anti-podoplanin antibody suppresses tumor metastasis through neutralization and antibody-dependent cellular cytotoxicity.
abstract: Podoplanin is a platelet aggregation-inducing factor associated with tumor metastasis, malignant progression, and cancer stem cells. We produced a rat-human chimeric anti-podoplanin mAb, NZ-8, from rat anti-podoplanin mAb (NZ-1). Although both NZ-1 and NZ-8 possess high binding affinities and high neutralizing activities of platelet aggregation, the antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity of NZ-8 were much higher than NZ-1. Furthermore, both NZ-1 and NZ-8 inhibited the growth of podoplanin-expressing tumors in vivo. Both NZ-1 and NZ-8 also suppressed hematogenous metastasis of podoplanin-expressing tumors. These results suggest that anti-podoplanin mAbs suppressed hematogenous metastasis by both neutralization and antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity activities. Targeting therapy to podoplanin-expressing tumors should be useful as a novel immunotherapy.
authors: Molecular Tumor Marker Research Team, Global COE Program, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Mika Kato
authors: MK
authors: Kaneko
authors: Akiko
authors: A
authors: Kunita
authors: Shinji
authors: S
authors: Abe
authors: Yuta
authors: Y
authors: Tsujimoto
authors: Masashi
authors: M
authors: Fukayama
authors: Kaoru
authors: K
authors: Goto
authors: Yoshihiko
authors: Y
authors: Sawa
authors: Yasuhiko
authors: Y
authors: Nishioka
authors: Yukinari
authors: Y
authors: Kato
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D016466:CHO Cells; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology; D006224:Cricetinae; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000494:pharmacology; D000098853:Podoplanin
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D003165:Complement System Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C117468:PDPN protein, human; D000098853:Podoplanin