Background & Aims
HCV patients who fail conventional interferon-based therapy have limited treatment
options. Dendritic cells are central to the priming and development of antigen-specific
CD4+ and CD8+ T cell immunity, necessary to elicit effective viral clearance. The aim of the study
was to investigate the safety and efficacy of vaccination with autologous dendritic
cells loaded with HCV-specific cytotoxic T cell epitopes.
Methods
We examined the potential of autologous monocyte-derived dendritic cells (MoDC), presenting
HCV-specific HLA A2.1-restricted cytotoxic T cell epitopes, to influence the course
of infection in six patients who failed conventional therapy. Dendritic cells were
loaded and activated ex vivo with lipopeptides. In this phase 1 dose escalation study, all patients received a
standard dose of cells by the intradermal route while sequential patients received
an increased dose by the intravenous route.
Results
No patient showed a severe adverse reaction although all experienced transient minor
side effects. HCV-specific CD8+ T cell responses were enumerated in PBMC by ELIspot for interferon-γ. Patients generated
de novo responses, not only to peptides presented by the cellular vaccine but also to additional
viral epitopes not represented in the lipopeptides, suggestive of epitope spreading.
Despite this, no increases in ALT levels were observed. However, the responses were
not sustained and failed to influence the viral load, the anti-HCV core antibody response
and the level of circulating cytokines.
Conclusions
Immunotherapy using autologous MoDC pulsed with lipopeptides was safe, but was unable
to generate sustained responses or alter the outcome of the infection. Alternative
dosing regimens or vaccination routes may need to be considered to achieve therapeutic
benefit.
Abbreviations:
HCV (hepatitis C virus), DC (dendritic cells), IFN (interferon), LN (lymph nodes), CTL (cytotoxic T lymphocyte), PBMC (peripheral blood mononuclear cells), SFC (spot forming cells), MoDC (monocyte-derived dendritic cells), IDU (intravenous drug user), ULN (upper limit of normal), ID (intradermal), IV (intravenous)Keywords
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Article info
Publication history
Published online: June 29, 2010
Accepted:
May 30,
2010
Received in revised form:
May 11,
2010
Received:
September 28,
2009
Identification
Copyright
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
