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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/33eb1d45a3ba4b309dbca6e1d44f59bf
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spelling	oai:doaj.org-article:33eb1d45a3ba4b309dbca6e1d44f59bf2021-12-02T14:23:49ZPD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma10.1038/s41698-021-00147-62397-768Xhttps://doaj.org/article/33eb1d45a3ba4b309dbca6e1d44f59bf2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00147-6https://doaj.org/toc/2397-768XAbstract 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.Naoya MaekawaSatoru KonnaiMaki NishimuraYumiko KagawaSatoshi TakagiKenji HosoyaHiroshi OhtaSangho KimTomohiro OkagawaYusuke IzumiTatsuya DeguchiYukinari KatoSatoshi YamamotoKeiichi YamamotoMikihiro TodaChie NakajimaYasuhiko SuzukiShiro MurataKazuhiko OhashiNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	pd-l1 immunohistochemistry for canine cancers and clinical benefit of anti-pd-l1 antibody in dogs with pulmonary metastatic oral malignant melanoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/33eb1d45a3ba4b309dbca6e1d44f59bf
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PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma

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