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 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.

• Authors: 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
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 8951 (08 21 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28827658 (Publication Type: Clinical Trial, Veterinary, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• B7-H1 Antigen

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacology)
• B7-H1 Antigen (antagonists & inhibitors)
• Cell Proliferation
• Cells, Cultured
• Dog Diseases (drug therapy, immunology)
• Dogs
• Dose-Response Relationship, Drug
• Female
• Immunotherapy
• Leukocytes, Mononuclear (cytology, drug effects, immunology)
• Male
• Melanoma (drug therapy, immunology, veterinary)
• Mouth Neoplasms (drug therapy, immunology, veterinary)
• Pilot Projects
• Sarcoma (drug therapy, immunology, veterinary)
• Treatment Outcome