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

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Title: A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
Authors: Maekawa, Naoya Browse this author
Konnai, Satoru Browse this author →KAKEN DB
Takagi, Satoshi Browse this author →KAKEN DB
Kagawa, Yumiko Browse this author
Okagawa, Tomohiro Browse this author
Nishimori, Asami Browse this author
Ikebuchi, Ryoyo Browse this author
Izumi, Yusuke Browse this author
Deguchi, Tatsuya Browse this author
Nakajima, Chie Browse this author →KAKEN DB
Kato, Yukinari Browse this author
Yamamoto, Keiichi Browse this author
Uemura, Hidetoshi Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Murata, Shiro Browse this author →KAKEN DB
Ohashi, Kazuhiko Browse this author →KAKEN DB
Issue Date: 21-Aug-2017
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 7
Start Page: 8951
Publisher DOI: 10.1038/s41598-017-09444-2
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.
Type: article
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鈴木 定彦

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