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

Abstract

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 CD4CD25CD127 regulatory T cells. Generated immune responses failed to provide virus elimination. Nevertheless, there were inverse correlations between viral load and NS3-specific proliferation (R = 0.62; p = 0.05) and IFN-γ secretion (R = - 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.

Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection

“…SARS-CoV-2 peptides are pulsed into an individual's monocytic-DCs and are then used to prime the same individual's T cells, resulting in SARS-CoV-2-specific T cells. These T cells may be cryopreserved or infused into the vulnerable individual as prevention or treatment against COVID-19 [66] , [67] , [68] . …”

Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response

“…It was shown that induction of T cell immune responses by DC vaccination is highly dependent on efficient antigen loading of the DCs [24]. The trials showed that such vaccines did not clear HCV infection in chronic hepatitis C patients despite induction of pronounced T-cell response [25,26]. Thus, the development of MSC vaccines based on genetic and cellular technologies could be one of the most promising strategies to prevent the spread of infectious diseases.…”

Modern antiviral biomedical cell products and their applications for COVID-19 therapy

“…Два клинических испытания I / II фаз терапевтических ДК-вакцин для лечения хронического гепатита С перечислены в базах данных ClinicalTrials.gov. В первом использовали аутологичные ДК, сгенерированные из моноцитов в присутствии интерферона α / ГМ-КСФ и пульсированных рекомбинантными белками ВГС Core (1-120) и NS3 (1192-1457) [38,39]. Исследование проводилось в Новосибирске (Российская Федерация), в нем участвовало 10 пациентов в возрасте от 18 до 65 лет.…”