Review
Gastroenterology & Hepatology
Grace L. H. Wong, Ed Gane, Anna S. F. Lok
Summary: Functional cure of hepatitis B is defined as sustained undetectable circulating HBsAg and HBV DNA after a finite course of treatment. Current therapies for HBV rarely achieve cure, but novel antiviral and immunomodulatory strategies show promise in increasing the chance of cure through personalized approaches. The development of safe, effective, and affordable curative therapies must be coupled with standardized virologic and immunologic assays to confirm target engagement and to assess response.
JOURNAL OF HEPATOLOGY
(2022)
Review
Gastroenterology & Hepatology
Scott Fung, Hannah S. J. Choi, Adam Gehring, Harry L. A. Janssen
Summary: Chronic HBV infection is a global health burden, and achieving a cure remains challenging due to the persistence of cccDNA, HBV-DNA integration, and impaired immune response. Current therapies include DAAs and immunomodulators, but there are still many obstacles to overcome for a complete cure of HBV.
Article
Gastroenterology & Hepatology
Hui Xu, Stephen Locarnini, Darren Wong, Rachel Hammond, Danni Colledge, Sally Soppe, Thao Huynh, Tim Shaw, Alexander J. Thompson, Peter A. Revill, P. Mark Hogarth, Bruce D. Wines, Renae Walsh, Nadia Warner
Summary: This study identified key anti-HBs profiles associated with either functional cure or failure to achieve functional cure in patients with chronic hepatitis B, suggesting a role for anti-HBs responses in functional cure.
JOURNAL OF HEPATOLOGY
(2022)
Article
Immunology
Wendi Zhang, Haoyu Sun, Rui Sun, Zhexiong Lian, Haiming Wei, Zhigang Tian, Yongyan Chen
Summary: This study utilized a xenogeneic mouse model to elucidate the immune tolerance mechanism of HBs transgenic mice to HBV. It was found that CD8(+) T cells from immunocompetent wild-type mice can accumulate in the liver of HBs transgenic mice, while the immune response in HBs transgenic mice is tolerant. Furthermore, CD4(+) T cells from the donor were shown to be necessary for the CD8(+) T cell response in the host spleen. CD4(+) T cells in the spleen of HBs transgenic mice displayed more tolerant features and directly suppressed CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Fritz Lai, Cherry Yong Yi Wee, Qingfeng Chen
Summary: Viral hepatitis, especially Hepatitis B Virus, remains a global health issue with vaccines being the primary preventive measure. Long term circulation of HBV can be detrimental to the liver and pose challenges to the human immune system.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Guilan Guo, Wenhui He, Zhongmin Zhou, Yan Diao, Jianhua Sui, Wenhui Li
Summary: Researchers generated HBV-specific CAR T cells based on an antibody 2H5-A14 targeting the PreS1 region of the HBV large envelope protein and showed that A14 CAR T cells have a highly specific killing effect on HBV-infected hepatocytes. Adoptive transfer of A14 CAR T cells to HBV-infected humanized FRG mice resulted in significant reductions of all serum and intrahepatic virological markers. A14 CAR T cell treatment also increased the levels of human IFN-γ, GM-CSF, and IL-8/CXCL-8 in the mice. These findings suggest that A14 CAR T cells may be further developed for curative therapy against HBV infection by eliminating infected hepatocytes and inducing the production of pro-inflammatory and antiviral cytokines.
Review
Virology
Takehisa Watanabe, Sanae Hayashi, Yasuhito Tanaka
Summary: Hepatitis B virus (HBV) is a significant cause of acute and chronic hepatitis worldwide. Current antiviral treatments do not always lead to a functional cure for chronic hepatitis B (CHB), so there is a need for new therapeutic agents. This review provides an overview of the developmental status of these drugs, particularly direct acting antiviral agents (DAAs), and highlights the importance of serological biomarkers and the measurement of covalently closed circular DNA (cccDNA) for predicting and monitoring CHB. Combination therapies and boosting immune response are also being explored.
Article
Immunology
Sophia Giang, David A. Horwitz, Sean Bickerton, Antonio La Cava
Summary: This study introduces a method to produce acellular tolerogenic aAPCs using PLGA nanoparticles, which can induce human T cells to become functional Tregs and modulate systemic autoimmunity. It highlights the potential of using PLGA NPs as a targeted approach to repair IL-2 and/or TGF-beta defects in autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Gastroenterology & Hepatology
Yong Chuan Tan, Guan Huei Lee, Daniel Q. Huang, Seng Gee Lim
Summary: HDV uses the HBV surface antigen to enter hepatocytes and is associated with accelerated fibrosis progression and increased risk of hepatocellular carcinoma. Current HBV antiviral agents have poor activity against HDV, therefore the search for drugs that can cure both HBV and HDV is needed.
LIVER INTERNATIONAL
(2023)
Article
Cell Biology
Otavio de Melo Espindola, Esther Siteur-van Rijnstra, Esmay Frankin, Kees Weijer, Yme Ubeles van der Velden, Ben Berkhout, Bianca Blom, Julien Villaudy
Summary: The study investigated early events in HTLV-1 pathogenesis using NSG mice reconstituted with a human immune system. HTLV-1 infection led to rapid increase in human T-cells, especially CD4(+)CD25(+) T-cells, in blood and lymphoid tissues. The infected mice displayed characteristics similar to human ATLL, suggesting that HTLV-1 infection modulates host immune responses to favor viral persistence.
Article
Engineering, Biomedical
Julian F. Ashby, Julien Schmidt, K. C. Neelima, Armand Kurum, Caroline Koch, Alexandre Harari, Li Tang, Sam H. Au
Summary: This study presents a novel microfluidic approach based on fluid shear stress to identify and recover highly potent T cell clones through probing cellular avidity. The method demonstrates efficient and rapid recovery of high-purity T cells from mixed populations, and markers of cytotoxicity, activation, and avidity persist upon exposure to fresh tumor cells.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Immunology
Qin Lin, Yiwei Zhong, Bin Wang
Summary: Chronic hepatitis B infection is a global health burden with risks for hepatocellular cancer and hepatic fibrosis. Elevated levels of immunosuppressive regulatory T cells (Tregs) in chronic hepatitis B virus (CHB) infection suppress effector T cell function and immune clearance against HBV. This study explored the potential use of mafosfamide (MAF) as an adjuvant to deplete Tregs in an HBV infection model. Administration of MAF reduced Tregs in HBV-infected mice and combined MAF with an anti-CHB protocol resulted in decreased Tregs, dendritic cell activation, increased HBV-specific T cell proliferation, and enhanced immune response. This therapeutic vaccine regimen showed promise in clearing HBV-associated antigens and achieving functional cure.
Review
Immunology
Connie B. Gilfillan, Michael Hebeisen, Nathalie Rufer, Daniel E. Speiser
Summary: The functional avidity (FA) of cytotoxic CD8 T cells plays a crucial role in their functional capabilities and protection from infection and cancer. The factors influencing FA and its regulation mechanisms are still not fully understood, but recent research suggests that FA may be stable in vivo due to continued signaling modulation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Veronica L. Nagle, Charli Ann J. Hertz, Kelly E. Henry, Maya S. Graham, Carl Campos, Nagavarakishore Pillarsetty, Andrea Schietinger, Ingo K. Mellinghoff, Jason S. Lewis
Summary: This study explores the use of anti-human-CD4 minibody for antibody-based PET to visualize human CD4(+) T cells. Through in vitro and in vivo experiments, it is found that this method can accurately detect CD4(+) T cells without impacting their abundance, proliferation, and activation state. In humanized mice, this method can also visualize the distribution of CD4(+) T cells in peripheral tissues and brain tumors.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Virology
Glenn Hogan, Benjamin Y. Winer, James Ahodantin, Julie Sellau, Tiffany Huang, Florian Douam, Masaya Funaki, Luis Chiriboga, Lishan Su, Alexander Ploss
Summary: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a major medical problem that can lead to severe liver disease. In a humanized mouse model, we found that HBV infection can prime and expand immune cells, leading to immune activation.
JOURNAL OF MEDICAL VIROLOGY
(2023)
