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

• Published in: Emerging microbes & infections Vol. 13; no. 1; p. 2387448
• Main Authors: Shi, Yang, Wang, Zihan, Xu, Jingjing, Niu, Wenxia, Wu, Yubin, Guo, Huiyu, Shi, Jinmiao, Li, Zonglin, Fu, Baorong, Hong, Yunda, Wang, Zikang, Guo, Wenjie, Chen, Dabing, Li, Xingling, Li, Qian, Wang, Shaojuan, Gao, Jiahua, Sun, Aling, Xiao, Yaosheng, Cao, Jiali, Fu, Lijuan, Wu, Yangtao, Zhang, Tianying, Xia, Ningshao, Yuan, Quan
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 31.12.2024
• Subjects: bispecific antibody; HBsAg suppression; Hepatitis B virus; TCR-like antibody; therapeutic antibody
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2024.2387448

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 recognising 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 fusing 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 and . 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.