Journal Article

Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours

Takeuchi, Hiroto, Kato, Yukinari, Ohashi, Kazuhiko, Kinoshita, Ryohei, Ohta, Hiroshi, Yamamoto, Satoshi, Hosoya, Kenji, Okagawa, Tomohiro, Murata, Shiro, Deguchi, Tatsuya, Owaki, Ryo, Kagawa, Yumiko, Kim, Sangho, Takagi, Satoshi, Suzuki, Yasuhiko, Maekawa, Naoya, Yamamoto, Keiichi, Konnai, Satoru, Tachibana, Yurika, Yokokawa, Madoka

2023

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenocarcinoma / Animals / Antibodies / Anticancer properties / Antitumor activity / Aspartate aminotransferase / B-cell lymphoma / Biology and Life Sciences / Bone cancer / Cancer therapies / Chemotherapy / Development and progression / Dogs / Drug dosages / Effectiveness / Health services / Hospitals, Animal / Hospitals, Teaching / Humans / Immune checkpoint inhibitors / Kidney cancer / Lymphocytes B / Lymphoma / Lymphomas / Malignancy / Medical research / Medicine and Health Sciences / Medicine, Experimental / Melanoma / Melanoma - drug therapy / Melanoma - pathology / Melanoma - veterinary / Melanoma, Cutaneous Malignant / Metastasis / Mouth Neoplasms - veterinary / Oncology / Oral cancer / Osteosarcoma / Osteosarcoma - drug therapy / Osteosarcoma - veterinary / PD-L1 protein / Radiation / Radiation therapy / Safety / Sarcoma / Skin cancer / Solid tumors / Surgery / Teaching hospitals / Thrombocytopenia / Transitional cell carcinoma / Treatment Outcome / Tumors / Ultrasonic imaging / Veterinary medicine / Viral antibodies