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Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection.
- Source :
-
Journal of Clinical Investigation . Aug2017, Vol. 127 Issue 8, p3177-3188. 12p. - Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LYMPHOCYTES
*T cell receptors
*HEPATITIS B virus
*HEPATITIS C virus
*T cells
*GENE expression
*MESSENGER RNA
*LABORATORY rats
*HEPATITIS B treatment
*RNA metabolism
*ANIMAL experimentation
*CELL receptors
*CYTOLOGICAL techniques
*EPITHELIAL cells
*HEPATITIS B
*HEPATITIS viruses
*HEPATOCELLULAR carcinoma
*IMMUNIZATION
*INFLAMMATION
*INTERFERONS
*LIVER
*LIVER tumors
*RESEARCH methodology
*MICE
*PROTEOLYTIC enzymes
*TISSUE culture
*VIRAL antigens
*ALANINE aminotransferase
*HAPLOTYPES
*GENE expression profiling
*CHRONIC hepatitis B
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 127
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 124499154
- Full Text :
- https://doi.org/10.1172/JCI93024