TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models

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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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Emerging Microbes and Infections
Subjects:
Hepatitis B virus
TCR-like antibody
bispecific antibody
therapeutic antibody
HBsAg suppression
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2024.2387448
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Summary: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.
ISSN:2222-1751

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