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Previously, we developed a rat anti\u2010human podoplanin mAb, NZ\u20101, and a rat\u2013human chimeric anti\u2010human podoplanin antibody, NZ\u20108, derived from NZ\u20101, which induced antibody\u2010dependent cellular cytotoxicity (ADCC) and complement\u2010dependent cytotoxicity against podoplanin\u2010positive MPM cell lines. In this study, we showed the antitumor effect of NZ\u20101, NZ\u20108, and NZ\u201012, a novel rat\u2013human chimeric anti\u2010human podoplanin antibody derived from NZ\u20101, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ\u20101 and rat NK (CD161a<jats:sup>+<\/jats:sup>) cells inhibited the growth of tumors and the production of pleural effusion in NCI\u2010H290\/PDPN or NCI\u2010H226 orthotopic xenograft mouse models. NZ\u20108 and human natural killer (NK) (CD56<jats:sup>+<\/jats:sup>) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ\u201012 induced potent ADCC mediated by human MNC, compared with either NZ\u20101 or NZ\u20108. Antitumor effects were observed following treatment with NZ\u201012 and human NK (CD56<jats:sup>+<\/jats:sup>) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ\u201012 mediated by human NK (CD56<jats:sup>+<\/jats:sup>) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin\u2010targeting immunotherapy using both NZ\u201012 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM.<\/jats:p>","DOI":"10.1111\/cas.12985","type":"journal-article","created":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T12:44:19Z","timestamp":1465821859000},"page":"1198-1205","source":"Crossref","is-referenced-by-count":49,"title":["Antitumor effect of novel anti\u2010podoplanin antibody NZ\u201012 against malignant pleural mesothelioma in an orthotopic xenograft model"],"prefix":"10.1111","volume":"107","author":[{"given":"Shinji","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Practice Pedagogy Institute of Biomedical Sciences Tokushima University Graduate School Tokushima Japan"},{"name":"Department of Respiratory Medicine and Rheumatology Institute of Biomedical Sciences Tokushima University Graduate School Tokushima 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