TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models
Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number o...
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Taylor & Francis Group
2024-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2387448 |
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| author | Yang Shi Zihan Wang Jingjing Xu Wenxia Niu Yubin Wu Huiyu Guo Jinmiao Shi Zonglin Li Baorong Fu Yunda Hong Zikang Wang Wenjie Guo Dabing Chen Xingling Li Qian Li Shaojuan Wang Jiahua Gao Aling Sun Yaosheng Xiao Jiali Cao Lijuan Fu Yangtao Wu Tianying Zhang Ningshao Xia Quan Yuan |
| author_facet | Yang Shi Zihan Wang Jingjing Xu Wenxia Niu Yubin Wu Huiyu Guo Jinmiao Shi Zonglin Li Baorong Fu Yunda Hong Zikang Wang Wenjie Guo Dabing Chen Xingling Li Qian Li Shaojuan Wang Jiahua Gao Aling Sun Yaosheng Xiao Jiali Cao Lijuan Fu Yangtao Wu Tianying Zhang Ningshao Xia Quan Yuan |
| author_sort | Yang Shi |
| collection | DOAJ |
| description | Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes in vitro and in vivo. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B. |
| format | Article |
| id | doaj-art-18b931e271c3464da761aa50c7b8336b |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-18b931e271c3464da761aa50c7b8336b2024-12-07T04:40:16ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2387448TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse modelsYang Shi0Zihan Wang1Jingjing Xu2Wenxia Niu3Yubin Wu4Huiyu Guo5Jinmiao Shi6Zonglin Li7Baorong Fu8Yunda Hong9Zikang Wang10Wenjie Guo11Dabing Chen12Xingling Li13Qian Li14Shaojuan Wang15Jiahua Gao16Aling Sun17Yaosheng Xiao18Jiali Cao19Lijuan Fu20Yangtao Wu21Tianying Zhang22Ningshao Xia23Quan Yuan24State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaDepartment of Infectious Disease, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaDepartment of Infectious Disease, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of ChinaDepartment of Infectious Disease, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaDepartment of Infectious Disease, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, People’s Republic of ChinaTherapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes in vitro and in vivo. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.https://www.tandfonline.com/doi/10.1080/22221751.2024.2387448Hepatitis B virusTCR-like antibodybispecific antibodytherapeutic antibodyHBsAg suppression |
| spellingShingle | Yang Shi Zihan Wang Jingjing Xu Wenxia Niu Yubin Wu Huiyu Guo Jinmiao Shi Zonglin Li Baorong Fu Yunda Hong Zikang Wang Wenjie Guo Dabing Chen Xingling Li Qian Li Shaojuan Wang Jiahua Gao Aling Sun Yaosheng Xiao Jiali Cao Lijuan Fu Yangtao Wu Tianying Zhang Ningshao Xia Quan Yuan TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models Emerging Microbes and Infections Hepatitis B virus TCR-like antibody bispecific antibody therapeutic antibody HBsAg suppression |
| title | TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models |
| title_full | TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models |
| title_fullStr | TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models |
| title_full_unstemmed | TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models |
| title_short | TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models |
| title_sort | tcr like bispecific antibodies toward eliminating infected hepatocytes in hbv mouse models |
| topic | Hepatitis B virus TCR-like antibody bispecific antibody therapeutic antibody HBsAg suppression |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2387448 |
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