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Sci Rep. 2017 Aug 21;7(1):8951. doi: 10.1038/s41598-017-09444-2.

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

Author information

1
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.
2
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. konnai@vetmed.hokudai.ac.jp.
3
Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0819, Japan.
4
North Lab, Sapporo, 003-0027, Japan.
5
Department of Diagnostic Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.
6
Research Center for Zoonosis Control, Hokkaido University, Sapporo, 001-0020, Japan.
7
Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, 001-0020, Japan.
8
Department of Antibody Drug Development, Graduate School of Medicine, Tohoku University, Sendai, 980-8575, Japan.
9
Project of Antibody Drug Development, New Industry Creation Hatchery Center, Sendai, 980-8575, Japan.
10
Research and Development Center, Fuso Pharmaceutical Industries, Ltd, Osaka, 536-0025, Japan.

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.

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