Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCV NS3 and Core proteins.
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.
Haller
Aurelia A
AA
GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO 80027, USA.
Lauer
Georg M
GM
King
Thomas H
TH
Kemmler
Charles
C
Fiolkoski
Valerie
V
Lu
Yingnian
Y
Bellgrau
Don
D
Rodell
Timothy C
TC
Apelian
David
D
Franzusoff
Alex
A
Duke
Richard C
RC
D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D016207:Cytokines; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C069130:nucleocapsid protein, Hepatitis C virus