Chronic Hepatitis BNCT07777250
Targeting ANKRD11 Reverses HBV-Specific CD8+ T Cell Dysfunction and Tolerance
An observational study of Chronic Hepatitis B, run by Beijing Municipal Administration of Hospitals.
Trial 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 positive T (CD8+ T) cells. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitis B
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Dec 2026to Aug 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 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.
Who may be able to join
- (1) Inclusion criteria for healthy donors: Age 18-60 years; Voluntary participation in this study and signing a written informed consent form; HLA-A11 positive; Generally in good health condition; No infection with hepatitis B virus, hepatitis C virus, HIV, syphilis, etc.; No severe liver, kidney, heart, lung, or blood system diseases; No recent immunosuppressive agents, cell therapy, or other treatments that may significantly affect immune function. (2) Inclusion criteria for chronic HBV patients: Age 18-65 years; Voluntary participation in this study and signing a written informed consent form; HLA-A11 positive; Meeting the diagnostic criteria for chronic HBV infection or chronic hepatitis B; HBsAg positive for ≥6 months; Able to provide basic clinical data, including HBsAg, HBeAg, HBV DNA, ALT, AST, etc.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Targeting ANKRD11 Reverses Hepatitis B Virus-Specific CD8 Positive T Lymphocyte Cell Dysfunction and Tolerance
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.
Read the detailed description
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.
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic Hepatitis B, CD8+ T Cell Exhaustion, ANKRD11, Epigenetic Regulation, TCR-T Cell Therapy
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Peripheral Blood Donors | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 4 hours of co-culture
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2026
- Study startDec 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Municipal Administration of Hospitals
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Minghui Li, Beijing Ditan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07777250
- Sponsor's protocol ID
- DTEC-KY2026-086-01
- Other IDs
- L2612037
- Status last verified
- Aug 2026
- First submitted
- 17 Aug 2026
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting ANKRD11 Reverses Hepatitis B Virus-Specific CD8 Positive T Lymphocyte Cell Dysfunction and Tolerance
- ClinicalTrials.gov ID
- NCT07777250
- Acronym / sponsor ID
- DTEC-KY2026-086-01
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic Hepatitis B, CD8+ T Cell Exhaustion, ANKRD11, Epigenetic Regulation, TCR-T Cell Therapy
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Beijing Municipal Administration of HospitalsOther government
- Study start
- Dec 2026 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 20 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Peripheral Blood Donors | – | –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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (1 listed)
- (1) Inclusion criteria for healthy donors: Age 18-60 years; Voluntary participation in this study and signing a written informed consent form; HLA-A11 positive; Generally in good health condition; No infection with hepatitis B virus, hepatitis C virus, HIV, syphilis, etc.; No severe liver, kidney, heart, lung, or blood system diseases; No recent immunosuppressive agents, cell therapy, or other treatments that may significantly affect immune function. (2) Inclusion criteria for chronic HBV patients: Age 18-65 years; Voluntary participation in this study and signing a written informed consent form; HLA-A11 positive; Meeting the diagnostic criteria for chronic HBV infection or chronic hepatitis B; HBsAg positive for ≥6 months; Able to provide basic clinical data, including HBsAg, HBeAg, HBV DNA, ALT, AST, etc.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Antigen-Specific Cytotoxic Activity of HBV-Specific TCR-T Cells
Time frame: After 4 hours of co-culture
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Hepatitis B, run by Beijing Municipal Administration of Hospitals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Minghui Li (010-84322078, wuhm2000@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antigen-Specific Cytotoxic Activity of HBV-Specific TCR-T Cells (time frame: After 4 hours of co-culture). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.