A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma

Abstract Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector fun...

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Autores principales: Naoya Maekawa, Satoru Konnai, Satoshi Takagi, Yumiko Kagawa, Tomohiro Okagawa, Asami Nishimori, Ryoyo Ikebuchi, Yusuke Izumi, Tatsuya Deguchi, Chie Nakajima, Yukinari Kato, Keiichi Yamamoto, Hidetoshi Uemura, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:0b6a85047df74aa79f76ad9d2aea96992021-12-02T15:06:12ZA canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma10.1038/s41598-017-09444-22045-2322https://doaj.org/article/0b6a85047df74aa79f76ad9d2aea96992017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09444-2https://doaj.org/toc/2045-2322Abstract Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.Naoya MaekawaSatoru KonnaiSatoshi TakagiYumiko KagawaTomohiro OkagawaAsami NishimoriRyoyo IkebuchiYusuke IzumiTatsuya DeguchiChie NakajimaYukinari KatoKeiichi YamamotoHidetoshi UemuraYasuhiko SuzukiShiro MurataKazuhiko OhashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Naoya Maekawa
Satoru Konnai
Satoshi Takagi
Yumiko Kagawa
Tomohiro Okagawa
Asami Nishimori
Ryoyo Ikebuchi
Yusuke Izumi
Tatsuya Deguchi
Chie Nakajima
Yukinari Kato
Keiichi Yamamoto
Hidetoshi Uemura
Yasuhiko Suzuki
Shiro Murata
Kazuhiko Ohashi
A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
description Abstract Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.
format article
author Naoya Maekawa
Satoru Konnai
Satoshi Takagi
Yumiko Kagawa
Tomohiro Okagawa
Asami Nishimori
Ryoyo Ikebuchi
Yusuke Izumi
Tatsuya Deguchi
Chie Nakajima
Yukinari Kato
Keiichi Yamamoto
Hidetoshi Uemura
Yasuhiko Suzuki
Shiro Murata
Kazuhiko Ohashi
author_facet Naoya Maekawa
Satoru Konnai
Satoshi Takagi
Yumiko Kagawa
Tomohiro Okagawa
Asami Nishimori
Ryoyo Ikebuchi
Yusuke Izumi
Tatsuya Deguchi
Chie Nakajima
Yukinari Kato
Keiichi Yamamoto
Hidetoshi Uemura
Yasuhiko Suzuki
Shiro Murata
Kazuhiko Ohashi
author_sort Naoya Maekawa
title A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
title_short A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
title_full A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
title_fullStr A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
title_full_unstemmed A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
title_sort canine chimeric monoclonal antibody targeting pd-l1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/0b6a85047df74aa79f76ad9d2aea9699
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