PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma
Abstract Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-021-00147-6 |
| _version_ | 1797421379819143168 |
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| author | Naoya Maekawa Satoru Konnai Maki Nishimura Yumiko Kagawa Satoshi Takagi Kenji Hosoya Hiroshi Ohta Sangho Kim Tomohiro Okagawa Yusuke Izumi Tatsuya Deguchi Yukinari Kato Satoshi Yamamoto Keiichi Yamamoto Mikihiro Toda Chie Nakajima Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi |
| author_facet | Naoya Maekawa Satoru Konnai Maki Nishimura Yumiko Kagawa Satoshi Takagi Kenji Hosoya Hiroshi Ohta Sangho Kim Tomohiro Okagawa Yusuke Izumi Tatsuya Deguchi Yukinari Kato Satoshi Yamamoto Keiichi Yamamoto Mikihiro Toda Chie Nakajima Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi |
| author_sort | Naoya Maekawa |
| collection | DOAJ |
| description | Abstract Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research. |
| first_indexed | 2024-03-09T07:15:03Z |
| format | Article |
| id | doaj.art-33eb1d45a3ba4b309dbca6e1d44f59bf |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T07:15:03Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-33eb1d45a3ba4b309dbca6e1d44f59bf2023-12-03T08:32:45ZengNature Portfolionpj Precision Oncology2397-768X2021-02-01511910.1038/s41698-021-00147-6PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanomaNaoya Maekawa0Satoru Konnai1Maki Nishimura2Yumiko Kagawa3Satoshi Takagi4Kenji Hosoya5Hiroshi Ohta6Sangho Kim7Tomohiro Okagawa8Yusuke Izumi9Tatsuya Deguchi10Yukinari Kato11Satoshi Yamamoto12Keiichi Yamamoto13Mikihiro Toda14Chie Nakajima15Yasuhiko Suzuki16Shiro Murata17Kazuhiko Ohashi18Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityNorth LabNorth LabVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Antibody Drug Development, Tohoku University Graduate School of MedicineDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido UniversityAbstract Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.https://doi.org/10.1038/s41698-021-00147-6 |
| spellingShingle | Naoya Maekawa Satoru Konnai Maki Nishimura Yumiko Kagawa Satoshi Takagi Kenji Hosoya Hiroshi Ohta Sangho Kim Tomohiro Okagawa Yusuke Izumi Tatsuya Deguchi Yukinari Kato Satoshi Yamamoto Keiichi Yamamoto Mikihiro Toda Chie Nakajima Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma npj Precision Oncology |
| title | PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma |
| title_full | PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma |
| title_fullStr | PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma |
| title_full_unstemmed | PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma |
| title_short | PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma |
| title_sort | pd l1 immunohistochemistry for canine cancers and clinical benefit of anti pd l1 antibody in dogs with pulmonary metastatic oral malignant melanoma |
| url | https://doi.org/10.1038/s41698-021-00147-6 |
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