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Therefore, a monoclonal antibody (mAb) against PDPN has been evaluated in preclinical models as a promising tumor therapy strategy. However, PDPN plays an essential role in normal development, such as in the development of the lungs. On\u2010target toxicity by anti\u2010PDPN mAbs to normal cells should be avoided to minimize adverse effects. A cancer\u2010specific mAb against PDPN, PMab\u2010117 (rat IgM, kappa), was previously established. This study engineered the humanized IgG\n                    <jats:sub>1<\/jats:sub>\n                    version (humPMab\u2010117) to investigate antitumor activity. Flow cytometry analysis confirmed that humPMab\u2010117 recognized PDPN\u2010overexpressed glioma LN229 (LN229\/PDPN) cells as well as PDPN\u2010positive PC\u201010 (human lung squamous cell carcinoma) and LN319 (human glioblastoma) cells. In contrast, humPMab\u2010117 did not react with normal epithelial cells from the lung bronchus, gingiva, mammary gland, corneal, and normal kidney podocytes, suggesting that humPMab\u2010117 retains cancer\u2010specific reactivity. Furthermore, humPMab\u2010117 effectively induced antibody\u2010dependent cellular cytotoxicity and complement\u2010dependent cytotoxicity against LN229\/PDPN, PC\u201010, and LN319 cells. In the xenograft tumor models, humPMab\u2010117 demonstrated strong antitumor efficacy. These results suggest the potential of humPMab\u2010117 as a therapeutic antibody for treating PDPN\u2010positive malignant tumors.\n                  <\/jats:p>","DOI":"10.1111\/cas.70103","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T18:40:01Z","timestamp":1747766401000},"page":"2232-2242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antitumor Activities by a Humanized Cancer\u2010Specific Anti\u2010Podoplanin Monoclonal Antibody\n                    <scp>humPMab<\/scp>\n                    \u2010117 Against Human Tumors"],"prefix":"10.1111","volume":"116","author":[{"given":"Tomohiro","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Antibody Drug Development Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2646-5132","authenticated-orcid":false,"given":"Hiroyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Antibody Drug Development Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9039-4474","authenticated-orcid":false,"given":"Tomokazu","family":"Ohishi","sequence":"additional","affiliation":[{"name":"Laboratory of Oncology, Institute of Microbial Chemistry (BIKAKEN) Microbial Chemistry Research Foundation  Shinagawa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9348-4240","authenticated-orcid":false,"given":"Manabu","family":"Kawada","sequence":"additional","affiliation":[{"name":"Laboratory of Oncology, Institute of Microbial Chemistry (BIKAKEN) Microbial Chemistry Research Foundation  Shinagawa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-9208","authenticated-orcid":false,"given":"Mika K.","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Antibody Drug Development Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5385-8201","authenticated-orcid":false,"given":"Yukinari","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Antibody Drug Development Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00690-x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/mab.2023.0033"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26031079"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158386"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031941"},{"key":"e_1_2_10_7_1","article-title":"268\u2009Development of FT825\/ONO\u20108250: An Off\u2010The\u2010Shelf CAR\u2010T Cell With Preferential HER2 Targeting and Engineered to Enable Multi\u2010Antigen Targeting, Improve Trafficking, and Overcome Immunosuppression","volume":"11","author":"Hosking M.","year":"2023","journal-title":"Journal for ImmunoTherapy of Cancer"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11030575"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030707"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309935200"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.12.044"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6598"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00332-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00283"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.03.010"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102976"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03218"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174362"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20211071"},{"key":"e_1_2_10_21_1","first-page":"514","article-title":"Podoplanin Promotes the Invasion of Oral Squamous Cell Carcinoma in Coordination With MT1\u2010MMP and Rho GTPases","volume":"5","author":"Li Y. 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