Induction of multi-functional T cells in a phase I clinical trial of dendritic cell immunotherapy in Hepatitis C virus infected individuals
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(Published version)
Date
2012
Authors
Li, S.
Roberts, S.
Plebanski, M.
Gouillou, M.
Spelman, T.
Latour, P.
Jackson, D.
Brown, L.
Sparrow, R.
Prince, H.
Editors
Shoukry, N.H.
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Journal article
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PLoS One, 2012; 7(8):1-7
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Shuo Li, Stuart Roberts, Magdalena Plebanski, Maelenn Gouillou, Tim Spelman, Philippe Latour, David Jackson, Lorena Brown, Rosemary L. Sparrow, H. Miles Prince, Derek Hart, Bruce E. Loveland and Eric J. Gowans
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Abstract
We have previously reported a world-first phase I clinical trial to treat HCV patients using monocyte-derived dendritic cells (Mo-DC) loaded with HCV-specific lipopeptides. While the brief treatment proved to be safe, it failed to reduce the viral load and induced only transient cell-mediated immune responses, measured by IFNc ELIspot. Here we reanalysed the PBMC samples from this trial to further elucidate the immunological events associated with the Mo-DC therapy. We found that HCV-specific single- and multi-cytokine secreting T cells were induced by the Mo-DC immunotherapy in some patients, although at irregular intervals and not consistently directed to the same HCV antigen. Despite the vaccination, the responses were generally poor in quality and comprised of primarily single-cytokine secreting cells. The frequency of FOXP3+ regulatory T cells (Treg) fluctuated following DC infusion and eventually dropped to below baseline by week 12, an interesting trend suggesting that the vaccination may have resulted in a more subtle outcome than was initially apparent. Our data suggested that Mo-DC therapy induced complex immune responses in vivo that may or may not lead to clinical benefit.
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Copyright: © 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.