Related Experiment Video
Updated: Jul 4, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral
Masaya Igase1, Sakuya Inanaga1, Shoma Nishibori1
1Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan.
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One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6.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.
Insights
The caninized anti-programmed death 1 (PD-1) antibody, ca-4F12-E6, shows a good safety profile in dogs with non-oral malignant melanoma solid tumors. While objective responses were limited, the treatment warrants further investigation in larger clinical trials.
Area of Science:
- Veterinary Oncology
- Immunotherapy
- Canine Cancer Research
Background:
- Anti-programmed death 1 (PD-1) antibodies offer durable responses in human cancers.
- Previous studies evaluated caninized anti-canine PD-1 antibody (ca-4F12-E6) in canine oral malignant melanoma (OMM).
- Therapeutic effects of ca-4F12-E6 on other canine tumors remained undetermined.
Purpose of the Study:
- To assess the safety and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors, excluding OMM.
- To evaluate treatment-related adverse events and tumor response rates.
Main Methods:
- Prospective enrollment of 38 dogs with non-OMM solid tumors.
- Treatment with ca-4F12-E6 at 3 mg/kg every two weeks for a 10-week cycle.
- Adverse events and efficacy graded per Veterinary Cooperative Oncology Group criteria.
Main Results:
- 37 dogs were evaluated for safety and efficacy; 13 (35.1%) experienced treatment-related adverse events.
- Two cases of sterile nodular panniculitis and one of myasthenia gravis/hypothyroidism were suspected immune-related adverse events.
- Overall response rate was 6.9% and clinical benefit rate was 27.6% in dogs with target lesions; median progression-free survival was 70 days and overall survival was 215 days.
Conclusions:
- Ca-4F12-E6 was well-tolerated in dogs with non-OMM solid tumors.
- A small number of dogs showed objective responses to ca-4F12-E6.
- Results support further large-scale clinical trials for anti-PD-1 antibody therapy in canine cancers.
