Clinical efficacy of anti-programmed death ligand 1 antibody HFC-L1/c4G12 in dogs with malignant tumors: an exploratory study
Cancer in dogs remains a major challenge in modern veterinary medicine. Immunotherapy using immune checkpoint inhibitors (ICIs) is available for various human tumor types, and recent veterinary clinical studies have shown that ICIs are a promising approach for treating canine cancers. A canine chimeric anti-PD-L1 antibody, c4G12 (HFC-L1), has been investigated for canine cancer immunotherapy; however, its clinical benefits have not been well characterized in tumors other than pulmonary metastatic (stage IV) oral malignant melanoma (OMM). To explore the efficacy and safety of HFC-L1, we conducted a clinical study in dogs with stage I-III OMM or other tumor types (n=12). HFC-L1 treatment at a dose of 5 mg/kg every 2 weeks was well tolerated, and no grade 3 or higher treatment-related adverse events were reported. Among the dogs eligible for response evaluation (n=10), a partial response was observed in one dog with squamous cell carcinoma, resulting in an objective response rate of 10%. In addition, in a dog with ceruminous cell carcinoma, clinical evidence of a tumor response was observed in metastatic lung lesions. Together, these results suggest that the HFC-L1 therapy is applicable for the treatment of various tumor types, although its clinical benefits should be further evaluated in clinical studies involving a larger number of dogs with each tumor type.
Authors
- Keiichi Yamamoto (ORCID: https://orcid.org/0000-0003-3278-5001)
- Takuya Furuta (ORCID: https://orcid.org/0000-0002-6645-7818)
- Hayato Nakamura (ORCID: https://orcid.org/0000-0003-2115-9873)
- Satoru Konnai (ORCID: https://orcid.org/0000-0002-3230-7109)
- Hiroto Takeuchi
- Tomohiro Okagawa (ORCID: https://orcid.org/0000-0002-1391-9732)
- Naoya Maekawa
- Satoshi Takagi (ORCID: https://orcid.org/0000-0001-6653-5890)
- Ryo Owaki (ORCID: https://orcid.org/0000-0002-9177-9325)
- Akinori Yamauchi (ORCID: https://orcid.org/0000-0001-6900-8949)
- Tomoyuki Abe (ORCID: https://orcid.org/0000-0001-6859-7614)
- Yukinari Kato (ORCID: https://orcid.org/0000-0001-5385-8201)
- Kenji Hosoya (ORCID: https://orcid.org/0000-0001-9208-3736)
- Ayano Kudo
- Kazuhiko Ohashi (ORCID: https://orcid.org/0000-0002-7513-640X)
- Michihito Tagawa (ORCID: https://orcid.org/0000-0003-1645-4413)
- Shiro Murata
- Yasuhiko Suzuki (ORCID: https://orcid.org/0000-0002-1313-1494)
- Yurika Tachibana
- Sangho Kim (ORCID: https://orcid.org/0000-0001-8451-4479)
- Tatsuya Deguchi (ORCID: https://orcid.org/0000-0002-9859-2299)
- Yumiko Kagawa (ORCID: https://orcid.org/0009-0006-0078-1443)
- S Kanazawa
- Shintaro Kamo (ORCID: https://orcid.org/0009-0004-5814-0791)
- Ryohei Kinoshita
- Madoka Yokokawa
Institutions
- Hokkaido University of Science (JP)
- Health Sciences University of Hokkaido (JP)
- Tohoku University (JP)
- Hokkaido University (JP)
- Department of Disease Control (TH)
- Advanced Pharma (US)
- Institut de Recherche Vaccinale (FR)
- Hokkaido Research Organization (JP)
- Veterinary Medical Center (JP)
- Hokkaido University Hospital (JP)
- Office of International Affairs (US)
- Fuso Pharmaceutical Industries (Japan) (JP)
- Azabu University (JP)
- Obihiro University of Agriculture and Veterinary Medicine (JP)
- Rakuno Gakuen University (JP)
- Global University (LB)
Publication Details
- Journal
- Journal of Veterinary Medical Science
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1292/jvms.25-0303
- Citations
- 1
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Japan Agency for Medical Research and Development
- Obihiro University of Agriculture and Veterinary Medicine
- Hokkaido University
- Japan Society for the Promotion of Science