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To develop a novel treatment for PM, podoplanin (PDPN), a transmembrane glycoprotein, has attracted significant attention because it is highly expressed in PM and is used for its diagnosis. We previously reported that NZ\u201012, a human chimeric antihuman PDPN antibody, exhibits antitumor effects against human PM cells through antibody\u2010dependent cellular cytotoxicity (ADCC) and complement\u2010dependent cytotoxicity (CDC). Additionally, we developed a cancer\u2010specific monoclonal antibody (CasMab) production technology and produced a mouse\u2010human chimeric cancer\u2010specific antihuman PDPN antibody, chLpMab\u20102, along with an afucosylated version, chLpMab\u20102f, to enhance ADCC activity. This study aimed to evaluate whether chLpMab\u20102f exhibits specific antitumor effects against PM in a preclinical model. We demonstrated that chLpMab\u20102f recognized the surface PDPN of human PM cell lines and human PM patient tissue but did not react with human normal tissues such as lung and kidney tissues. Furthermore, these antibodies exhibited ADCC and CDC activity against PDPN\u2010positive PM cells while showing reduced toxicity toward non\u2010malignant kidney\u2010derived PDPN\u2010positive cells, such as HEK\u2010293FT. Additionally, chLpMab\u20102f demonstrated stronger ADCC activity through more efficient NK cell activation in comparison to chLpMab\u20102. Moreover, chLpMab\u20102f suppressed tumor progression in subcutaneously and intrathoracically transplanted human PM cells in mice. These findings suggest that PDPN\u2010targeting immunotherapy with chLpMab\u20102f generated by CasMab technology could provide an effective treatment for PM with decreased toxicity toward normal tissues.<\/jats:p>","DOI":"10.1111\/cas.70325","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T02:10:12Z","timestamp":1768961412000},"page":"917-928","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer\u2010Specific Antihuman Podoplanin Antibody\n                    <scp>chLpMab<\/scp>\n                    \u20102f Exerts Antitumor Effects Against Pleural Mesothelioma"],"prefix":"10.1111","volume":"117","author":[{"given":"Aito","family":"Yoshida","sequence":"first","affiliation":[{"name":"Departments of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences Tokushima University  Tokushima 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