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Type: Journal article
Title: Induction of multi-functional T cells in a phase I clinical trial of dendritic cell immunotherapy in Hepatitis C virus infected individuals
Author: Li, S.
Roberts, S.
Plebanski, M.
Gouillou, M.
Spelman, T.
Latour, P.
Jackson, D.
Brown, L.
Sparrow, R.
Prince, H.
Hart, D.
Loveland, B.
Gowans, E.
Citation: PLoS One, 2012; 7(8):1-7
Publisher: Public Library of Science
Issue Date: 2012
ISSN: 1932-6203
Statement of
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
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.
Keywords: Dendritic Cells; Leukocytes, Mononuclear; T-Lymphocytes; Monocytes; Humans; Hepacivirus; Hepatitis C; Antigens, Viral; Cytokines; Immunotherapy; Adult; Middle Aged; Female; Male; Forkhead Transcription Factors; Interferon-gamma; Lipopeptides; Enzyme-Linked Immunospot Assay; Cell- and Tissue-Based Therapy; CD3 Complex
Rights: 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.
RMID: 0020121511
DOI: 10.1371/journal.pone.0039368
Grant ID:
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