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Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors

  • Masaya Igase (Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University) ;
  • Sakuya Inanaga (Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University) ;
  • Shoma Nishibori (Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University) ;
  • Kazuhito Itamoto (Laboratory of Veterinary Small Animal Clinical Science, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Hiroshi Sunahara (Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Yuki Nemoto (Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Kenji Tani (Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Hiro Horikirizono (Laboratory of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Munekazu Nakaichi (Laboratory of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Kenji Baba (Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Satoshi Kambayashi (Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Masaru Okuda (Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Yusuke Sakai (Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Masashi Sakurai (Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University) ;
  • Masahiro Kato (Nippon Zenyaku Kogyo Co., Ltd.) ;
  • Toshihiro Tsukui (Nippon Zenyaku Kogyo Co., Ltd.) ;
  • Takuya Mizuno (Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University)
  • Received : 2023.06.05
  • Accepted : 2023.12.17
  • Published : 2024.01.31

Abstract

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Keywords

Acknowledgement

The authors would like to acknowledge the all YUAMEC clinical staff and the laboratory members for helping us succeed in the present study. Finally, we thank the dogs and their owners for making this study possible.

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