Improvement of a dendritic cell-based tumour vaccine by an influenza virus.
BACKGROUND
Induction of cytotoxic T cells by dendritic cells (DCs) is a promising approach to tumour-immunotherapy. A standardized effective preparation of DCs remains a challenge for clinical application.


METHODS
We assessed whether influenza A partial NS1 deletion (NS1-124) - or complete NS1 deletion (delNS1) vaccine viruses can be employed to enhance monocyte-derived dendritic cell (MODC)-based T-cell stimulation directed against malignant cells in vitro.


RESULTS
Infection of cultures containing human MODCs and CD3(+) T cells with NS1 deletion viruses led to an increased induction of type I interferons and IL-6 compared with infection with wild-type virus. This correlated with the fact that infection of MODCs with NS1 deletion viruses but not with wild type virus led to stimulation of a cytotoxic T-cell (CTL) response against the Panc-1 cells, which were used as cell lysate to prime the MODCs. Moreover, stimulation of MODCs with Panc-1 tumour cell lysate obtained via lysis with the complete deletion virus delNS1, but not with the partial NS1 deletion virus also enhanced the CTL response against the tumour cells. Induction of function CTL response in those assays correlated with an increased proliferation of CD8(+) T cells.


CONCLUSIONS
The pro-inflammatory capacity of influenza NS1 deletion vaccine viruses could serve as an adjuvant-like agent to improve preparations of MODC-based anti-cancer vaccines. The complete NS1 deletion virus appears to be more potent as adjuvant when used for production of tumour lysates.
Sachet
M
M
Medical University of Vienna, 1090 Vienna, Austria.
Friedl
J
J
Hassler
M
M
Ploder
M
M
Stary
G
G
Stift
A
A
Bergmann
M
M
D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines