Abstract | BACKGROUND & AIMS: METHODS: We designed chimeric T-cell receptors directed against HBV surface proteins present on HBV-infected cells and used them to graft primary human T cells with antibody-like specificity. The receptors were composed of a single chain antibody fragment directed against HBV S or L protein fused to intracellular signalling domains of CD3xi and the costimulatory CD28 molecule. RESULTS: Our results show that these chimeric receptors, when retrovirally delivered and expressed on the cell surface, enable primary human T cells to recognize HBsAg-positive hepatocytes, release interferon gamma and interleukin 2, and, most importantly, lyse HBV replicating cells. When coincubated with HBV-infected primary human hepatocytes, these engineered, antigen-specific T cells selectively eliminated HBV-infected and thus cccDNA-positive target cells. CONCLUSIONS: Elimination of HBV cccDNA-positive hepatocytes following antiviral therapy is a major therapeutic goal in chronic hepatitis B, and adoptive transfer of grafted T cells provides a promising novel therapeutic approach. However, T-cell therapy may also cause liver damage and therefore needs further preclinical evaluation.
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Authors | Felix Bohne, Markus Chmielewski, Gregor Ebert, Katja Wiegmann, Timo Kürschner, Andreas Schulze, Stephan Urban, Martin Krönke, Hinrich Abken, Ulrike Protzer |
Journal | Gastroenterology
(Gastroenterology)
Vol. 134
Issue 1
Pg. 239-47
(Jan 2008)
ISSN: 1528-0012 [Electronic] United States |
PMID | 18166356
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD3 Complex
- CD3xi antigen, human
- Hepatitis B Surface Antigens
- Immunoglobulin Fragments
- Receptors, Antigen, T-Cell
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Topics |
- CD3 Complex
(immunology)
- Cell Culture Techniques
- Chimera
- Hepatitis B
(immunology, pathology)
- Hepatitis B Surface Antigens
(immunology)
- Hepatitis B virus
(physiology)
- Hepatocytes
(immunology)
- Humans
- Immunoglobulin Fragments
(physiology)
- Receptors, Antigen, T-Cell
(immunology)
- T-Cell Antigen Receptor Specificity
(physiology)
- T-Lymphocytes
(physiology)
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