An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1
Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1–targeting antibody–drug conjugate (ADC) was generated, in which a humanized anti-CADM1 e...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Molecular & Cellular Oncology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/23723556.2024.2399379 |
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| author | Man Hagiyama Azusa Yoneshige Tomoyuki Otani Akihiro Wada Fuka Takeuchi Yuji Shoya Takao Inoue Akihiko Ito |
| author_facet | Man Hagiyama Azusa Yoneshige Tomoyuki Otani Akihiro Wada Fuka Takeuchi Yuji Shoya Takao Inoue Akihiko Ito |
| author_sort | Man Hagiyama |
| collection | DOAJ |
| description | Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1–targeting antibody–drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1–MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1–MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1–MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium. |
| format | Article |
| id | doaj-art-97c6f10550dc4a26964a6818ee0e8df5 |
| institution | OA Journals |
| issn | 2372-3556 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Molecular & Cellular Oncology |
| spelling | doaj-art-97c6f10550dc4a26964a6818ee0e8df52025-08-20T02:38:14ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562024-12-0111110.1080/23723556.2024.2399379An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1Man Hagiyama0Azusa Yoneshige1Tomoyuki Otani2Akihiro Wada3Fuka Takeuchi4Yuji Shoya5Takao Inoue6Akihiko Ito7Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, JapanDepartment of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, JapanDepartment of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, JapanDepartment of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, JapanDivision of Molecular Pathology, Graduate School of Medicine, Kindai University, Osaka-sayama, Osaka, JapanDivision of Molecular Pathology, Graduate School of Medicine, Kindai University, Osaka-sayama, Osaka, JapanDepartment of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, JapanDepartment of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, JapanCell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1–targeting antibody–drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1–MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1–MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1–MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.https://www.tandfonline.com/doi/10.1080/23723556.2024.2399379CADM1early-stage cancerendometrial hyperplasiafertility preservationgynecologic oncology |
| spellingShingle | Man Hagiyama Azusa Yoneshige Tomoyuki Otani Akihiro Wada Fuka Takeuchi Yuji Shoya Takao Inoue Akihiko Ito An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 Molecular & Cellular Oncology CADM1 early-stage cancer endometrial hyperplasia fertility preservation gynecologic oncology |
| title | An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 |
| title_full | An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 |
| title_fullStr | An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 |
| title_full_unstemmed | An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 |
| title_short | An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 |
| title_sort | antibody drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1 |
| topic | CADM1 early-stage cancer endometrial hyperplasia fertility preservation gynecologic oncology |
| url | https://www.tandfonline.com/doi/10.1080/23723556.2024.2399379 |
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