Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma
Although immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for the treatment of canine malignant melanoma, desirable clinical efficacies have not been achieved. Recent studies in humans have suggested that radiation therapy (RT) com...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/11/3013 |
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| author | Tatsuya Deguchi Naoya Maekawa Satoru Konnai Ryo Owaki Kenji Hosoya Keitaro Morishita Motoji Nakamura Tomohiro Okagawa Hiroto Takeuchi Sangho Kim Ryohei Kinoshita Yurika Tachibana Madoka Yokokawa Satoshi Takagi Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi |
| author_facet | Tatsuya Deguchi Naoya Maekawa Satoru Konnai Ryo Owaki Kenji Hosoya Keitaro Morishita Motoji Nakamura Tomohiro Okagawa Hiroto Takeuchi Sangho Kim Ryohei Kinoshita Yurika Tachibana Madoka Yokokawa Satoshi Takagi Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi |
| author_sort | Tatsuya Deguchi |
| collection | DOAJ |
| description | Although immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for the treatment of canine malignant melanoma, desirable clinical efficacies have not been achieved. Recent studies in humans have suggested that radiation therapy (RT) combined with ICIs induces robust systemic antitumour immunity in patients with cancer. This study retrospectively examined the therapeutic efficacy of combination therapy (hypofractionated RT and anti-PD-L1 antibody [c4G12]) in dogs with pulmonary metastatic oral malignant melanoma. The intrathoracic clinical benefit rate (CBR)/median overall survival (OS) in the no RT (<i>n</i> = 20, free from the effect of RT), previous RT (<i>n</i> = 9, received RT ≤8 weeks prior to the first c4G12 dose), and concurrent RT (<i>n</i> = 10, c4G12 therapy within ±1 week of the first RT fraction) groups were 10%/185 days, 55.6%/283.5 days (<i>p</i> < 0.05 vs. no RT group), and 20%/129 days (<i>p</i> > 0.05 vs. no RT group), respectively. The adverse events were considered to be tolerable in the combination therapy. Thus, hypofractionated RT before the initiation of c4G12 therapy can be an effective approach for enhancing the therapeutic efficacy of immunotherapy, with acceptable safety profiles. Further prospective clinical studies are required to confirm the findings of this study. |
| first_indexed | 2024-03-11T03:10:29Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:10:29Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-553eb6b242424cc2918749f9ddb192002023-11-18T07:39:38ZengMDPI AGCancers2072-66942023-06-011511301310.3390/cancers15113013Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant MelanomaTatsuya Deguchi0Naoya Maekawa1Satoru Konnai2Ryo Owaki3Kenji Hosoya4Keitaro Morishita5Motoji Nakamura6Tomohiro Okagawa7Hiroto Takeuchi8Sangho Kim9Ryohei Kinoshita10Yurika Tachibana11Madoka Yokokawa12Satoshi Takagi13Yukinari Kato14Yasuhiko Suzuki15Shiro Murata16Kazuhiko Ohashi17Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanDepartment of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanVeterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0819, JapanDepartment of Veterinary Surgery 1, School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, JapanDepartment of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanInternational Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, JapanDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanDepartment of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanAlthough immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for the treatment of canine malignant melanoma, desirable clinical efficacies have not been achieved. Recent studies in humans have suggested that radiation therapy (RT) combined with ICIs induces robust systemic antitumour immunity in patients with cancer. This study retrospectively examined the therapeutic efficacy of combination therapy (hypofractionated RT and anti-PD-L1 antibody [c4G12]) in dogs with pulmonary metastatic oral malignant melanoma. The intrathoracic clinical benefit rate (CBR)/median overall survival (OS) in the no RT (<i>n</i> = 20, free from the effect of RT), previous RT (<i>n</i> = 9, received RT ≤8 weeks prior to the first c4G12 dose), and concurrent RT (<i>n</i> = 10, c4G12 therapy within ±1 week of the first RT fraction) groups were 10%/185 days, 55.6%/283.5 days (<i>p</i> < 0.05 vs. no RT group), and 20%/129 days (<i>p</i> > 0.05 vs. no RT group), respectively. The adverse events were considered to be tolerable in the combination therapy. Thus, hypofractionated RT before the initiation of c4G12 therapy can be an effective approach for enhancing the therapeutic efficacy of immunotherapy, with acceptable safety profiles. Further prospective clinical studies are required to confirm the findings of this study.https://www.mdpi.com/2072-6694/15/11/3013hypofractionated radiation therapyanti-PD-L1 antibodyimmune checkpoint blockadecanine malignant melanomaimmunotherapy |
| spellingShingle | Tatsuya Deguchi Naoya Maekawa Satoru Konnai Ryo Owaki Kenji Hosoya Keitaro Morishita Motoji Nakamura Tomohiro Okagawa Hiroto Takeuchi Sangho Kim Ryohei Kinoshita Yurika Tachibana Madoka Yokokawa Satoshi Takagi Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma Cancers hypofractionated radiation therapy anti-PD-L1 antibody immune checkpoint blockade canine malignant melanoma immunotherapy |
| title | Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma |
| title_full | Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma |
| title_fullStr | Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma |
| title_full_unstemmed | Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma |
| title_short | Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma |
| title_sort | enhanced systemic antitumour immunity by hypofractionated radiotherapy and anti pd l1 therapy in dogs with pulmonary metastatic oral malignant melanoma |
| topic | hypofractionated radiation therapy anti-PD-L1 antibody immune checkpoint blockade canine malignant melanoma immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/11/3013 |
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