Induction of multi-functional T cells in a phase I clinical trial of dendritic cell immunotherapy in hepatitis C virus infected individuals.
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 IFNγ 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.
Burnet Institute, Melbourne, Victoria, Australia. shuo.li@burnet.edu.au
Shuo
S
Li
Stuart
S
Roberts
Magdalena
M
Plebanski
Maelenn
M
Gouillou
Tim
T
Spelman
Philippe
P
Latour
David
D
Jackson
Lorena
L
Brown
Rosemary L
RL
Sparrow
H Miles
HM
Prince
Derek
D
Hart
Bruce E
BE
Loveland
Eric J
EJ
Gowans
D000328:Adult; D000956:Antigens, Viral / Q000737:chemistry; D017252:CD3 Complex / Q000096:biosynthesis; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D055666:Lipopeptides / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*
D000956:Antigens, Viral; D017252:CD3 Complex; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D055666:Lipopeptides; D007371:Interferon-gamma