An observational study in Chronic Hepatitis B, sponsored by Beijing Municipal Administration of Hospitals. Not yet recruiting. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-28.
Sponsored by Beijing Municipal Administration of Hospitals · Observational
Achieving a functional cure for chronic hepatitis B (CHB) is largely hindered by the irreversible functional exhaustion and immune tolerance of hepatitis B virus (HBV)-specific CD8 positive T (CD8+ T) cells. In investigators previous studies, an in vivo Clustered Regularly Interspaced Short Palindromic Repeat(CRISPR) screen identified ANKRD11 for the first time as an "epigenetic brake" on CD8+ T-cell effector function. Loss of ANKRD11 markedly enhanced the expansion, effector function, and viral clearance capacity of HBV-specific T cells. Based on these findings, investigators hypothesize that ANKRD11 regulates the epigenetic program of T-cell exhaustion by restricting the activity of AP-1 family transcription factors, and that targeting ANKRD11 can reverse T-cell dysfunction and overcome immune tolerance.
This project will: (1) elucidate the epigenetic mechanisms by which ANKRD11 regulates T-cell exhaustion using conditional knockout mouse models and multi-omics approaches; (2) evaluate how ANKRD11 deficiency reshapes the differentiation trajectory and antiviral function of HBV-specific T cells in models of chronic HBV infection; and (3) develop a combinatorial gene-editing strategy integrating "release of the brake" with "stepping on the accelerator" to generate enhanced T Cell Receptor-T cell Therapy(TCR-T) cells and evaluate their efficacy and safety in humanized mouse models. The study is expected to define a novel mechanism by which ANKRD11 regulates T-cell exhaustion, establish an enhanced TCR-T therapeutic strategy, and provide a potential approach toward achieving a functional cure for chronic HBV infection.
The human participant component of this study is limited to prospective collection of peripheral blood samples from patients with chronic hepatitis B and healthy volunteers for preclinical laboratory investigations. No therapeutic intervention is assigned to human participants. The major experimental components of the overall research project are conducted in vitro and in animal models.
HLA-A11+ healthy donors or patients with chronic HBV infection providing peripheral blood for isolation of CD8+ T cells; Presence of acute infection or other conditions that may substantially affect T-cell function; Inability to provide an adequate peripheral blood sample or insufficient viable CD8+ T cells for laboratory analyses.
Exclusion Criteria:
(1) Exclusion criteria for healthy donors: HLA-A11 negative; having concurrent infections such as HBV, HCV, HIV, syphilis, etc.; having autoimmune diseases, malignant tumors or severe chronic diseases; having recently used glucocorticoids, immunosuppressants, biological agents or undergone cell therapy; pregnant or lactating women; having obvious anemia, abnormal coagulation function or conditions unsuitable for blood collection; researchers consider them unsuitable to participate in this study. (2) Exclusion criteria for chronic HBV patients: HLA-A11 negative; having concurrent infections such as HCV, HDV, HIV or syphilis; having other clear liver diseases such as autoimmune liver disease, alcoholic liver disease, drug-induced liver injury, genetic metabolic liver disease, etc.; having liver cell carcinoma or other malignant tumors; having decompensated liver cirrhosis or severe liver failure; having severe heart, lung, kidney or blood system diseases; pregnant or lactating women; having recently received systemic immunosuppressants, biological agents or cell therapy; having severe anemia, abnormal coagulation function or other conditions unsuitable for blood collection; researchers consider them unsuitable to participate in this study.
HLA-A11+ healthy donors or patients with chronic HBV infection will provide peripheral blood for isolation of CD8+ T cells. No study intervention will be assigned or administered to the participants. The isolated CD8+ T cells will be used for ex vivo TCR-T cell generation and subsequent functional evaluation.
Antigen-Specific Cytotoxic Activity of HBV-Specific TCR-T Cells
Antigen-specific cytotoxic activity of HBV-specific TCR-T cells will be assessed using HBc141-151 peptide-loaded T2-A11 target cells at effector-to-target ratios of 1:1, 2.5:1, 5:1, and 10:1 by LDH release assay and flow cytometry-based cytotoxicity assay.
Time frame: After 4 hours of co-culture
No study locations are listed for this record.
Plan to share: No
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Beijing Municipal Administration of Hospitals