ArticleHepatology (Baltimore, Md.)2020
Immune-Mobilizing Monoclonal T Cell Receptors Mediate Specific and Rapid Elimination of Hepatitis B-Infected Cells.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- HIV-1 virome profiling using HIV-PULSE to guide therapeutic and curative interventions.EBioMedicine · 2026Article
- Safety and biologic activity of a bispecific T cell receptor targeting HIV Gag in males living with HIV: a first-in-human trial.Nature communications · 2026Article
- PD-1/PD-L1 blockade as part of combination strategies toward functional cure of chronic hepatitis B.Frontiers in immunology · 2026Review
- The Expanding Role of HLA-E in Host Defense: A Target for Broadly Applicable Vaccines and Immunotherapies.Cells · 2025Review
- Article
- Emerging therapies for HBsAg seroclearance: spotlight on novel combination strategies.Hepatology international · 2025Review
- Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies.Antibodies (Basel, Switzerland) · 2025Review
- Prospect of emerging treatments for hepatitis B virus functional cure.Clinical and molecular hepatology · 2025Review
- [Screening and functional identification of HLA-A*24:02-restricted HBsAg-specific TCR based on single-cell TCRαβ double-stranded amplification pairing].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models.Emerging microbes & infections · 2024Article
- Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.Nature communications · 2024Article
- Broadening alloselectivity of T cell receptors by structure guided engineering.Scientific reports · 2024Article
- An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives.Journal of hematology & oncology · 2024Review
- Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Nucleos(T)ide Analogue Treatment Has a More Pronounced Impact on Immune Repertoires of CHB Patients Compared to HCC Patients.Journal of inflammation research · 2024Article
- New Treatment Options in Chronic Hepatitis B: How Close Are We to Cure?Infectious diseases & clinical microbiology · 2023Review
- Challenges and solutions for therapeutic TCR-based agents.Immunological reviews · 2023Review
- Redirecting Polyclonal T Cells against Cancer with Soluble T-Cell Receptors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Current Best Practice in Hepatitis B Management and Understanding Long-term Prospects for Cure.Gastroenterology · 2023Review
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Authors and funding
31 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsTherapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBV-specific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinity-enhanced T Cell receptor with an anti-CD3 T Cell-activating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virus-derived peptides presented by human leukocyte antigen (HLA). APPROACH AND
resultsImmTAV molecules specific for HLA-A*02:01-restricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAV-Env to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imaging-based killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAV-Env can redirect T cells from healthy and HBV-infected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAV-Env redirection of T cells induced cytolysis of antigen-positive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA.
conclusionsThe ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous non-HBV-specific T cells, bypassing exhausted HBV-specific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.