Safety and clinical efficacy of an anti-PD-L1 antibody

• Published in: PloS one Vol. 18; no. 10; p. e0291727
• Main Authors: Maekawa, Naoya, Konnai, Satoru, Hosoya, Kenji, Kim, Sangho, Kinoshita, Ryohei, Deguchi, Tatsuya, Owaki, Ryo, Tachibana, Yurika, Yokokawa, Madoka, Takeuchi, Hiroto, Kagawa, Yumiko, Takagi, Satoshi, Ohta, Hiroshi, Kato, Yukinari, Yamamoto, Satoshi, Yamamoto, Keiichi, Suzuki, Yasuhiko, Okagawa, Tomohiro, Murata, Shiro, Ohashi, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Public Library of Science 04.10.2023
• Subjects: Antibodies; Care and treatment; Development and progression; Dogs; Health aspects; Lymphomas; Medical research; Medicine, Experimental; Melanoma; Patient outcomes; Sarcoma; Tumors; Viral antibodies; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0291727

Immune checkpoint inhibitors (ICIs) have been developed for canine tumour treatment, and pilot clinical studies have demonstrated their antitumour efficacy in dogs with oral malignant melanoma (OMM). Although ICIs have been approved for various human malignancies, their clinical benefits in other tumour types remain to be elucidated in dogs. Here, we conducted a clinical study of c4G12, a canine chimeric anti-PD-L1 antibody, to assess its safety and efficacy in dogs with various advanced malignant tumours (n = 12) at the Veterinary Teaching Hospital of Hokkaido University from 2018 to 2023. Dogs with digit or foot pad malignant melanoma (n = 4), osteosarcoma (n = 2), hemangiosarcoma (n = 1), transitional cell carcinoma (n = 1), nasal adenocarcinoma (n = 1), B-cell lymphoma (n = 1), or undifferentiated sarcoma (n = 2) were treated with 2 or 5 mg/kg c4G12 every 2 weeks. Treatment-related adverse events of any grade were observed in eight dogs (66.7%), including elevated aspartate aminotransferase (grade 3) in one dog (8.3%) and thrombocytopenia (grade 4) in another dog (8.3%). Among dogs with target disease at baseline (n = 8), as defined by the response evaluation criteria for solid tumours in dogs (cRECIST), one dog with nasal adenocarcinoma and another with osteosarcoma experienced a partial response (PR), with an objective response rate of 25.0% (2 PR out of 8 dogs; 95% confidence interval: 3.2-65.1%). These results suggest that c4G12 is safe and tolerable and shows antitumor effects in dogs with malignant tumours other than OMM. Further clinical studies are warranted to identify the tumour types that are most likely to benefit from c4G12 treatment.