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August 7, 2017

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August 7, 2017

Breakthrough immunotherapy for Chronic Hepatitis B virus infection

Aug. 7, 2017 — Professor Antonio Bertoletti (Scientific Founder) and Dr Sarene Koh (Product Development Director) of Lion TCR Pte Ltd in Singapore together with Professor Maura Dandri and Dr. Janine Kah of University Medical Center Hamburg and various Singapore & German institutions, published their finding on the effective control of chronic hepatitis B (CHB) infection with T cell immunotherapy in the July issue of the Journal of Clinical Investigation (see reference to JCI article below). CHB has severe quantitative and functional defects in HBV-specific T cell response. Restoration of the HBV specific T cells are determinant to clear the virus of CHB. The team is the first to use mRNA transduction to engineer the transient HBV specific TCR-redirected T cells as a new therapeutic strategy against CHB. The research utilizes molecular biology techniques to modify the T cells of a patient. When infused back into the patient’s body, the TCR redirected T lymphocytes find, recognize and inhibit or clear the hepatitis B virus in hepatocytes.

Hepatitis B is a viral infection of the liver that is a major global health problem. More than 250 million people are chronic hepatitis B (CHB) carriers and approximately 1 million people die every year from CHB-related diseases. There is an urgent need to design new strategies to eliminate and achieve functional cure of chronic HBV infection.

Various current therapies for HCC only inhibit the virus without clearance of the virus, patients continue to live under the danger of complications which many eventually die from.

This study, a collaborative effort between Duke-NUS, various prestigious Singapore & German institutions and Lion TCR, provides a potential solution to control the HBV infection, potentially complete clearance of HBV virus and possibly leading to a cure for CHB. The research uses proprietary technologies from Lion TCR Pte Ltd on TCR-T cell therapy invented by Prof Antonio Bertoletti. PR Newswire

Reference:
Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection.
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lutgehetmann, Antonio Bertoletti, and Maura Dandri. J Clin Invest. 2017 Aug 1;127(8):3177-3188

Abstract – Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice. We assessed virological and gene-expression changes using quantitative reverse-transcriptase PCR (qRT-PCR), immunofluorescence, and Luminex technology. HBV-specific T cells lysed HBV-producing hepatoma cells in vitro. In vivo, 3 injections of HBV-specific T cells caused progressive viremia reduction within 12 days of treatment in animals reconstituted with haplotype-matched hepatocytes, whereas viremia remained stable in mice receiving irrelevant T cells redirected toward hepatitis C virus-specific TCRs. Notably, increases in alanine aminotransferase levels, apoptotic markers, and human inflammatory cytokines returned to pretreatment levels within 9 days after the last injection. T cell transfer did not trigger inflammation in uninfected mice. These data support the feasibility of using mRNA electroporation to engineer HBV TCR-redirected T cells in patients with chronic HBV infection. PubMed