{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T01:37:50Z","timestamp":1769132270153,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Podoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). We previously reported the generation of a rat anti-human podoplanin Ab, NZ-1, which inhibited podoplanin-induced platelet aggregation and hematogenous metastasis. In this study, we examined the antitumor effector functions of NZ-1 and NZ-8, a novel rat-human chimeric Ab generated from NZ-1 including Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against MPM in vitro and in vivo. Immunostaining with NZ-1 showed the expression of podoplanin in 73% (11 out of 15) of MPM cell lines and 92% (33 out of 36) of malignant mesothelioma tissues. NZ-1 could induce potent ADCC against podoplanin-positive MPM cells mediated by rat NK (CD161a+) cells, but not murine splenocytes or human mononuclear cells. Treatment with NZ-1 significantly reduced the growth of s.c. established tumors of MPM cells (ACC-MESO-4 or podoplanin-transfected MSTO-211H) in SCID mice, only when NZ-1 was administered with rat NK cells. In in vivo imaging, NZ-1 efficiently accumulated to xenograft of MPM, and its accumulation continued for 3 wk after systemic administration. Furthermore, NZ-8 preferentially recognized podoplanin expressing in MPM, but not in normal tissues. NZ-8 could induce higher ADCC mediated by human NK cells and complement-dependent cytotoxicity as compared with NZ-1. Treatment with NZ-8 and human NK cells significantly inhibited the growth of MPM cells in vivo. These results strongly suggest that targeting therapy to podoplanin with therapeutic Abs (i.e., NZ-8) derived from NZ-1 might be useful as a novel immunotherapy against MPM.<\/jats:p>","DOI":"10.4049\/jimmunol.1300448","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T02:55:11Z","timestamp":1369104911000},"page":"6239-6249","source":"Crossref","is-referenced-by-count":83,"title":["A Novel Targeting Therapy of Malignant Mesothelioma Using Anti-Podoplanin Antibody"],"prefix":"10.1093","volume":"190","author":[{"given":"Shinji","family":"Abe","sequence":"first","affiliation":[{"name":"Central Office for Clinical Pharmacy Training, Institute of Health Biosciences, University of Tokushima Graduate School , Tokushima 770-8503,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tokushima University Hospital , Tokushima 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