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

Autor:	Shi Y; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Wang Z; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Xu J; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Niu W; Department of Infectious Disease, Xiang'an Hospital of Xiamen University, Xiamen University, Xiamen, People's Republic of China., Wu Y; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Guo H; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Shi J; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Li Z; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Fu B; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Hong Y; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Wang Z; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Guo W; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Chen D; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Li X; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Li Q; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Wang S; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Gao J; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Sun A; Department of Infectious Disease, Xiang'an Hospital of Xiamen University, Xiamen University, Xiamen, People's Republic of China., Xiao Y; Department of Infectious Disease, Xiang'an Hospital of Xiamen University, Xiamen University, Xiamen, People's Republic of China., Cao J; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China.; Department of Clinical Laboratory, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, People's Republic of China., Fu L; Department of Infectious Disease, Xiang'an Hospital of Xiamen University, Xiamen University, Xiamen, People's Republic of China., Wu Y; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Zhang T; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China., Xia N; State 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 China., Yuan Q; State 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 China.; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostic, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, People's Republic of China.
Jazyk:	angličtina
Zdroj:	Emerging microbes & infections [Emerg Microbes Infect] 2024 Dec; Vol. 13 (1), pp. 2387448. Date of Electronic Publication: 2024 Aug 08.
DOI:	10.1080/22221751.2024.2387448
Abstrakt:	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.
Databáze:	MEDLINE
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