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GPC1 plays essential roles in regulating various signaling pathways involved in tumor cell proliferation, invasiveness, and tumorigenesis. Overexpression of GPC1 in tumors mediates oncogenic transformation, epithelial-to-mesenchymal transition, metastatic dissemination, and therapeutic resistance. Accordingly, GPC1-targeted therapeutic strategies have been investigated in clinical and preclinical studies. However, clinical efficacy has been limited. We previously developed an anti-GPC1 monoclonal antibody (mAb), G1Mab-28 (mouse IgG1, \u03ba), which exhibits high affinity and specificity for GPC1. In the present study, we generated recombinant isotype-converted G1Mab-28, including G1Mab-28-mG2a (mouse IgG2a) and G1Mab-28-hG1 (human IgG1). Both mAbs recognized GPC1-expressing human tumor cell lines, including lung squamous cell carcinoma PC-10 and pancreatic ductal adenocarcinoma PK-45H, by flow cytometry. Moreover, both mAbs exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against those cell lines. In mouse xenograft models, treatment with the mAbs resulted in potent antitumor efficacy against PC-10 and PK-45H tumors. Collectively, these findings support the therapeutic potential of G1Mab-28 for the treatment of GPC1-positive tumors.<\/jats:p>","DOI":"10.3390\/ijms27104181","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:10:52Z","timestamp":1778267452000},"page":"4181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chimeric Anti-Glypican 1 Antibodies Exert Antitumor Activities in Xenograft Models of Lung and Pancreatic Cancers"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7579-0453","authenticated-orcid":false,"given":"Haruto","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, 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, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, 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":"Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-7322","authenticated-orcid":false,"given":"Hiroyuki","family":"Satofuka","sequence":"additional","affiliation":[{"name":"Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, 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, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, 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, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70029","DOI":"10.1002\/pgr2.70029","article-title":"Structural Features of Glypicans and their Impact on Wnt Signaling in Cancer","volume":"3","author":"Tsao","year":"2025","journal-title":"Proteoglycan Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C694","DOI":"10.1152\/ajpcell.00045.2022","article-title":"The function of glypicans in the mammalian embryo","volume":"322","author":"Filmus","year":"2022","journal-title":"Am. 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