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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0291727 |
| _version_ | 1797665391998140416 |
|---|---|
| author | Naoya Maekawa Satoru Konnai Kenji Hosoya Sangho Kim Ryohei Kinoshita Tatsuya Deguchi Ryo Owaki Yurika Tachibana Madoka Yokokawa Hiroto Takeuchi Yumiko Kagawa Satoshi Takagi Hiroshi Ohta Yukinari Kato Satoshi Yamamoto Keiichi Yamamoto Yasuhiko Suzuki Tomohiro Okagawa Shiro Murata Kazuhiko Ohashi |
| author_facet | Naoya Maekawa Satoru Konnai Kenji Hosoya Sangho Kim Ryohei Kinoshita Tatsuya Deguchi Ryo Owaki Yurika Tachibana Madoka Yokokawa Hiroto Takeuchi Yumiko Kagawa Satoshi Takagi Hiroshi Ohta Yukinari Kato Satoshi Yamamoto Keiichi Yamamoto Yasuhiko Suzuki Tomohiro Okagawa Shiro Murata Kazuhiko Ohashi |
| author_sort | Naoya Maekawa |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T19:43:11Z |
| format | Article |
| id | doaj.art-295c408651194fcf866d2177d2d31e14 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T19:43:11Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-295c408651194fcf866d2177d2d31e142023-10-06T05:32:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011810e029172710.1371/journal.pone.0291727Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours.Naoya MaekawaSatoru KonnaiKenji HosoyaSangho KimRyohei KinoshitaTatsuya DeguchiRyo OwakiYurika TachibanaMadoka YokokawaHiroto TakeuchiYumiko KagawaSatoshi TakagiHiroshi OhtaYukinari KatoSatoshi YamamotoKeiichi YamamotoYasuhiko SuzukiTomohiro OkagawaShiro MurataKazuhiko OhashiImmune 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.https://doi.org/10.1371/journal.pone.0291727 |
| spellingShingle | Naoya Maekawa Satoru Konnai Kenji Hosoya Sangho Kim Ryohei Kinoshita Tatsuya Deguchi Ryo Owaki Yurika Tachibana Madoka Yokokawa Hiroto Takeuchi Yumiko Kagawa Satoshi Takagi Hiroshi Ohta Yukinari Kato Satoshi Yamamoto Keiichi Yamamoto Yasuhiko Suzuki Tomohiro Okagawa Shiro Murata Kazuhiko Ohashi Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0291727 |
| work_keys_str_mv | AT naoyamaekawa safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT satorukonnai safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT kenjihosoya safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT sanghokim safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT ryoheikinoshita safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT tatsuyadeguchi safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT ryoowaki safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT yurikatachibana safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT madokayokokawa safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT hirototakeuchi safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT yumikokagawa safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT satoshitakagi safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT hiroshiohta safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT yukinarikato safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT satoshiyamamoto safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT keiichiyamamoto safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT yasuhikosuzuki safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT tomohirookagawa safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT shiromurata safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours AT kazuhikoohashi safetyandclinicalefficacyofanantipdl1antibodyc4g12indogswithadvancedmalignanttumours |