Immunotherapy with interferon-α-induced dendritic cells for chronic HCV infection (the results of pilot clinical trial).

Autor: Chernykh, Elena, Leplina, Olga, Oleynik, Ekaterina, Tikhonova, Marina, Tyrinova, Tamara, Starostina, Natalia, Ostanin, Alexandr
Zdroj: Immunologic Research; Feb2018, Vol. 66 Issue 1, p31-43, 13p
Abstrakt: The key role of T cells in hepatitis C virus (HCV) elimination and the ability of dendritic cells (DCs) to induce antiviral T cell responses suggest that DC vaccines could be a promising approach in the treatment of chronic HCV infection. The aim of our study was to evaluate, whether immunotherapy with DCs is safe and elicits anti-HCV T cell responses. Ten patients with HCV (genotype 1) were vaccinated with monocyte-derived DCs, generated in the presence of IFN-α (IFN-DCs) and pulsed with recombinant HCV Core and NS3 proteins. Treatment schedule included four subcutaneous vaccinations with 1 week interval and six vaccinations with month interval. No serious adverse events or an increase in hepatitis C biochemical activity were registered after vaccination. Using ex vivo assays for the detection of proliferative responses, IFN-γ production and CD8+ degranulation have shown that immunotherapy elicited antigen-specific responses in all patients although individual heterogeneity existed within their types, magnitude, and timing. Core/NS3-specific proliferative response and CD8+ T cell degranulation have already been registered after the first course of vaccination. Of note, Core-specific responses had higher magnitude. The appearance of antigen-specific IFN-γ responses was registered after the second vaccination course. Vaccination did not cause Th2 response and expansion of the CD4+CD25+CD127− regulatory T cells. Generated immune responses failed to provide virus elimination. Nevertheless, there were inverse correlations between viral load and NS3-specific proliferation (RS = 0.62; p = 0.05) and IFN-γ secretion (RS = − 0.82; p = 0.001) at 6-month post-treatment period. Immunotherapy with IFN-DCs was safe and elicited HCV-specific T cell responses which were insufficient to eliminate viruses but could be implicated in the restriction of viral replication. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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