Anti-podoplanin antibody against MPM
Abe, Shinji Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kato Kaneko, Mika Tohoku University
Tsuchihashi, Yuki Tokushima University
Izumi, Toshihiro Tokushima University
Ogasawara, Satsohi Tohoku University
Sato, Chiemi Tokushima University Tokushima University Educator and Researcher Directory
Otsuka, Kenji Tokushima University
Tsuchiya, Koichiro Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kato, Yukinari Tohoku University
antibody-dependent cellular cytotoxicity
orthotopic xenograft model
Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat–human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ- 8, and NZ-12, a novel rat–human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a+) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56+) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56+) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56+) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM.
Japanese Cancer Association
© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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