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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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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. |
format | Online Article Text |
id | pubmed-10550157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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