| Autor: |
Tomohiro Okagawa, Satoru Konnai, Shinya Goto, Yamato Sajiki, Otgontuya Ganbaatar, Kei Watari, Hayato Nakamura, Cai-Xia Wang, Taro Tachibana, Yukinari Kato, Yayoi Kameda, Junko Kohara, Nobuhiro Terasaki, Manabu Kubota, Akira Takeda, Hirofumi Takahashi, Yasuhiko Suzuki, Naoya Maekawa, Shiro Murata, Kazuhiko Ohashi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Veterinary Research, Vol 54, Iss 1, Pp 1-14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1297-9716 |
| DOI: |
10.1186/s13567-023-01213-6 |
| Popis: |
Abstract Immune checkpoint molecules PD-1/PD-L1 cause T-cell exhaustion and contribute to disease progression in chronic infections of cattle. We established monoclonal antibodies (mAbs) that specifically inhibit the binding of bovine PD-1/PD-L1; however, conventional anti-PD-1 mAbs are not suitable as therapeutic agents because of their low binding affinity to antigen. In addition, their sensitivity for the detection of bovine PD-1 is low and their use for immunostaining PD-1 is limited. To address these issues, we established two anti-bovine PD-1 rabbit mAbs (1F10F1 and 4F5F2) and its chimeric form using bovine IgG1 (Boch1D10F1), which exhibit high binding affinity. One of the rabbit mAb 1D10F1 binds more strongly to bovine PD-1 compared with a conventional anti-PD-1 mAb (5D2) and exhibits marked inhibitory activity on the PD-1/PD-L1 interaction. In addition, PD-1 expression in bovine T cells could be detected with higher sensitivity by flow cytometry using 1D10F1. Furthermore, we established higher-producing cells of Boch1D10F1 and succeeded in the mass production of Boch1D10F1. Boch1D10F1 exhibited a similar binding affinity to bovine PD-1 and the inhibitory activity on PD-1/PD-L1 binding compared with 1D10F1. The immune activation by Boch1D10F1 was also confirmed by the enhancement of IFN-γ production. Finally, Boch1D10F1 was administered to bovine leukemia virus-infected cows to determine its antiviral effect. In conclusion, the high-affinity anti-PD-1 antibody developed in this study represents a powerful tool for detecting and inhibiting bovine PD-1 and is a candidate for PD-1-targeted immunotherapy in cattle. |
| Databáze: |
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| Externí odkaz: |
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