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

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 tu...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550157/
https://www.ncbi.nlm.nih.gov/pubmed/37792729
http://dx.doi.org/10.1371/journal.pone.0291727
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author 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
author_facet 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
author_sort Maekawa, Naoya
collection PubMed
description 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.
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spelling pubmed-105501572023-10-05 Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours 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 PLoS One Research Article 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. Public Library of Science 2023-10-04 /pmc/articles/PMC10550157/ /pubmed/37792729 http://dx.doi.org/10.1371/journal.pone.0291727 Text en © 2023 Maekawa et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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
Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
title Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
title_full Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
title_fullStr Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
title_full_unstemmed Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
title_short Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
title_sort safety and clinical efficacy of an anti-pd-l1 antibody (c4g12) in dogs with advanced malignant tumours
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550157/
https://www.ncbi.nlm.nih.gov/pubmed/37792729
http://dx.doi.org/10.1371/journal.pone.0291727
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