Abstract |
Control of primary infection with hepatitis C virus (HCV) is associated with robust and broad T cell immunity. In contrast, chronic infection is characterized by weak T cell responses suggesting that an approach that boosts these responses could be a therapeutic advance. Saccharomyces cerevisiae is an effective inducer of innate and adaptive cellular immunity and we have generated recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein. Pre-clinical studies in mice showed that GI-5005 induced potent antigen-specific proliferative and cytotoxic T cell responses that were associated with Th1-type cytokine secretion. In studies in which GI-5005 was administered up to 13 times, no detectable vector neutralization or induction of tolerance was observed. Prophylactic as well as therapeutic administration of GI-5005 in mice led to eradication of tumor cells expressing HCV NS3 protein. Immunotherapy with GI-5005 is being evaluated in chronic HCV infected individuals in a Phase 1 clinical trial.
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Authors | Aurelia A Haller, Georg M Lauer, Thomas H King, Charles Kemmler, Valerie Fiolkoski, Yingnian Lu, Don Bellgrau, Timothy C Rodell, David Apelian, Alex Franzusoff, Richard C Duke |
Journal | Vaccine
(Vaccine)
Vol. 25
Issue 8
Pg. 1452-63
(Feb 09 2007)
ISSN: 0264-410X [Print] Netherlands |
PMID | 17098335
(Publication Type: Journal Article)
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Chemical References |
- Cytokines
- NS3 protein, hepatitis C virus
- Recombinant Fusion Proteins
- Viral Core Proteins
- Viral Hepatitis Vaccines
- Viral Nonstructural Proteins
- nucleocapsid protein, Hepatitis C virus
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Topics |
- Animals
- Cell Line, Tumor
- Cytokines
(immunology, metabolism)
- HeLa Cells
- Hepacivirus
(genetics, immunology)
- Hepatitis C
(immunology, prevention & control)
- Humans
- Immunotherapy
(methods)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Recombinant Fusion Proteins
(genetics, immunology)
- Saccharomyces cerevisiae
(genetics, immunology, metabolism)
- T-Lymphocytes, Cytotoxic
(immunology)
- T-Lymphocytes, Helper-Inducer
(immunology)
- Viral Core Proteins
(biosynthesis, genetics, immunology)
- Viral Hepatitis Vaccines
(genetics, immunology)
- Viral Nonstructural Proteins
(biosynthesis, genetics, immunology)
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