Ren Nanamiya, Tomokazu Ohishi, Hiroyuki Suzuki, Takuya Mizuno, Takeo Yoshikawa, Teizo Asano, Tomohiro Tanaka, Mika K Kaneko, Yukinari Kato
{"title":"去聚焦小鼠-犬嵌合抗人表皮生长因子受体2单克隆抗体(H77Bf)在犬骨肉瘤小鼠异种移植模型中发挥抗肿瘤活性","authors":"Ren Nanamiya, Tomokazu Ohishi, Hiroyuki Suzuki, Takuya Mizuno, Takeo Yoshikawa, Teizo Asano, Tomohiro Tanaka, Mika K Kaneko, Yukinari Kato","doi":"10.1089/mab.2022.0022","DOIUrl":null,"url":null,"abstract":"<p><p>Human epidermal growth factor receptor 2 (HER2) has been studied in many human cancer types, and its overexpression and/or gene mutation contribute to the poor prognosis. Therefore, HER2 is an important therapeutic target in various cancer types, including breast and gastric cancers. We previously developed an anti-HER2 monoclonal antibody (mAb), H<sub>2</sub>Mab-77 (mouse IgG<sub>1</sub>, kappa), which detects HER2 and dog HER2 (dHER2) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-HER2 mAb (H77Bf), and investigated the reactivity against canine osteosarcoma D-17 cells by flow cytometry. Furthermore, we showed that H77Bf exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells <i>in vitro</i> and exhibited the potent antitumor activity <i>in vivo</i>. These results suggest that H77Bf exerts antitumor effects against dHER2-expressing canine tumors and could be valuable as part of an antibody treatment regimen for them.</p>","PeriodicalId":53514,"journal":{"name":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","volume":"42 1","pages":"27-33"},"PeriodicalIF":0.0000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Defucosylated Mouse-Dog Chimeric Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody (H77Bf) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma.\",\"authors\":\"Ren Nanamiya, Tomokazu Ohishi, Hiroyuki Suzuki, Takuya Mizuno, Takeo Yoshikawa, Teizo Asano, Tomohiro Tanaka, Mika K Kaneko, Yukinari Kato\",\"doi\":\"10.1089/mab.2022.0022\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Human epidermal growth factor receptor 2 (HER2) has been studied in many human cancer types, and its overexpression and/or gene mutation contribute to the poor prognosis. Therefore, HER2 is an important therapeutic target in various cancer types, including breast and gastric cancers. We previously developed an anti-HER2 monoclonal antibody (mAb), H<sub>2</sub>Mab-77 (mouse IgG<sub>1</sub>, kappa), which detects HER2 and dog HER2 (dHER2) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-HER2 mAb (H77Bf), and investigated the reactivity against canine osteosarcoma D-17 cells by flow cytometry. Furthermore, we showed that H77Bf exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells <i>in vitro</i> and exhibited the potent antitumor activity <i>in vivo</i>. These results suggest that H77Bf exerts antitumor effects against dHER2-expressing canine tumors and could be valuable as part of an antibody treatment regimen for them.</p>\",\"PeriodicalId\":53514,\"journal\":{\"name\":\"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy\",\"volume\":\"42 1\",\"pages\":\"27-33\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1089/mab.2022.0022\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Monoclonal Antibodies in Immunodiagnosis and Immunotherapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/mab.2022.0022","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
Human epidermal growth factor receptor 2 (HER2) has been studied in many human cancer types, and its overexpression and/or gene mutation contribute to the poor prognosis. Therefore, HER2 is an important therapeutic target in various cancer types, including breast and gastric cancers. We previously developed an anti-HER2 monoclonal antibody (mAb), H2Mab-77 (mouse IgG1, kappa), which detects HER2 and dog HER2 (dHER2) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-HER2 mAb (H77Bf), and investigated the reactivity against canine osteosarcoma D-17 cells by flow cytometry. Furthermore, we showed that H77Bf exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells in vitro and exhibited the potent antitumor activity in vivo. These results suggest that H77Bf exerts antitumor effects against dHER2-expressing canine tumors and could be valuable as part of an antibody treatment regimen for them.
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