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Targeting ANKRD11 Reverses HBV-Specific CD8+ T Cell Dysfunction and Tolerance

NCT07777250 · Status: NOT_YET_RECRUITING · Type: OBSERVATIONAL · Enrollment: 3

Last updated 2026-08-20

No results posted yet for this study

Summary

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+ T cells. In our previous studies, an in vivo 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, we 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 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.

Conditions

Sponsors & Collaborators

  • Beijing Municipal Administration of Hospitals

    lead OTHER_GOV

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2026-12-31
Primary Completion
2028-06-30
Completion
2028-08-31

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07777250 on ClinicalTrials.gov