Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCV NS3 and Core proteins.

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Haller AA, Lauer GM, King TH, Kemmler C, Fiolkoski V, Lu Y, Bellgrau D, Rodell TC, Apelian D, Franzusoff A, Duke RC

Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCV NS3 and Core proteins.

Vaccine. 2007 Feb 9;25(8):1452-63. Epub 2006 Nov 10.

PubMed ID
17098335 [ View in PubMed
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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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