Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model
Abstract Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to dev...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-90770-1 |
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| author | Min-young Song Jaewon Cho Hyosung Park Yujeong Song Keon Kim Jae-Hee Ahn Chang-Min Lee Dae Hee Kim Hyun-Jeong Ko |
| author_facet | Min-young Song Jaewon Cho Hyosung Park Yujeong Song Keon Kim Jae-Hee Ahn Chang-Min Lee Dae Hee Kim Hyun-Jeong Ko |
| author_sort | Min-young Song |
| collection | DOAJ |
| description | Abstract Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to develop PD-L1-specific antibodies using phage display technology for treating canine cancer. A synthetic antibody library was screened, and 18 high-affinity single-chain variable fragment clones were subsequently converted to the IgG format for enhancing binding affinity and functional stability. The clone #15 exhibited the highest binding affinity and most pronounced antitumor effects. The PD-1/PD-L1 interaction was inhibited by antibody #15. The binding and thermal stabilities of the antibodies were validated by flow cytometry and thermal stability assays, respectively. In NOG mice xenografted with canine osteosarcoma cells and treated with canine peripheral blood mononuclear cells and antibody #15, the tumor size and weight were reduced. Antibody #15 significantly increased apoptosis of tumor cells and lymphocyte populations. Therefore, anti-PD-L1 antibodies, particularly antibody #15, have substantial potential as novel immunotherapeutic agents against canine osteosarcoma. This study represents a significant advancement in veterinary oncology, with the potential of improving treatment outcomes for canine cancers and providing insights into similar strategies in human cancer therapy. |
| format | Article |
| id | doaj-art-0899d131657c4d3ba6aba281f34f7802 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0899d131657c4d3ba6aba281f34f78022025-08-20T02:59:24ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-90770-1Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft modelMin-young Song0Jaewon Cho1Hyosung Park2Yujeong Song3Keon Kim4Jae-Hee Ahn5Chang-Min Lee6Dae Hee Kim7Hyun-Jeong Ko8Department of Pharmacy, Kangwon National UniversityDepartment of Pharmacy, Kangwon National UniversityDepartment of Pharmacy, Kangwon National UniversityDepartment of Pharmacy, Kangwon National UniversityDepartment of Veterinary Internal Medicine, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National UniversityDepartment of Pharmacy, Kangwon National UniversityDepartment of Veterinary Internal Medicine, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National UniversityDepartment of Pharmacy, Kangwon National UniversityDepartment of Pharmacy, Kangwon National UniversityAbstract Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to develop PD-L1-specific antibodies using phage display technology for treating canine cancer. A synthetic antibody library was screened, and 18 high-affinity single-chain variable fragment clones were subsequently converted to the IgG format for enhancing binding affinity and functional stability. The clone #15 exhibited the highest binding affinity and most pronounced antitumor effects. The PD-1/PD-L1 interaction was inhibited by antibody #15. The binding and thermal stabilities of the antibodies were validated by flow cytometry and thermal stability assays, respectively. In NOG mice xenografted with canine osteosarcoma cells and treated with canine peripheral blood mononuclear cells and antibody #15, the tumor size and weight were reduced. Antibody #15 significantly increased apoptosis of tumor cells and lymphocyte populations. Therefore, anti-PD-L1 antibodies, particularly antibody #15, have substantial potential as novel immunotherapeutic agents against canine osteosarcoma. This study represents a significant advancement in veterinary oncology, with the potential of improving treatment outcomes for canine cancers and providing insights into similar strategies in human cancer therapy.https://doi.org/10.1038/s41598-025-90770-1Canine cancerProgrammed death ligand 1ImmunotherapeuticsAntibodyPhage display |
| spellingShingle | Min-young Song Jaewon Cho Hyosung Park Yujeong Song Keon Kim Jae-Hee Ahn Chang-Min Lee Dae Hee Kim Hyun-Jeong Ko Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model Scientific Reports Canine cancer Programmed death ligand 1 Immunotherapeutics Antibody Phage display |
| title | Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model |
| title_full | Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model |
| title_fullStr | Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model |
| title_full_unstemmed | Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model |
| title_short | Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model |
| title_sort | discovery and functional characterization of canine pd l1 targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model |
| topic | Canine cancer Programmed death ligand 1 Immunotherapeutics Antibody Phage display |
| url | https://doi.org/10.1038/s41598-025-90770-1 |
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