Therapeutic @entity5 vaccines need to stimulate a refractory immune system to make an effective anti- @entity5 response. We have explored the use of lentiviral vectors to deliver @entity5 antigen genes to dendritic cells (DC) as a possible mechanism of immune stimulation. Direct injection of a lentiviral vector encoding the melanoma antigen @entity16051 in HLA-A2 @entity19 primed @entity16051 -specific CD8+ cells that could be expanded by boosting with an @entity16051 @entity6621 . The expanded cells could kill @entity16051 (157-165) peptide-pulsed targets in vivo. In order to examine the priming step directly, we constructed another lentiviral vector expressing the melanoma antigen Melan-A ( @entity3059 ). Here we show that Melan-A protein is also efficiently expressed after transduction of @entity1 DC cultured from peripheral blood mononuclear cells. When these transduced DC are co-cultured with autologous na  ve T cells, they cause the expansion of cells that recognise the HLA-A2 restricted Melan-A(27-35) epitope. The expanded cells are functional in that they release @entity379 upon antigen stimulation. Melan-A lentiviral vector transduced DC caused a similar level of na  ve T-cell expansion to Melan-A(27-35) peptide-pulsed DC in four experiments using different HLA-A2 positive donors. These data suggest that a vaccine based either on DC transduced with a lentiviral vector ex vivo, or on direct lentiviral vector injection, should be assessed in a phase I clinical trial.

Lentiviral vector expression of XXXX antigens in dendritic cells as an immunotherapeutic strategy.

@entity1 :: ('9606', 'Species') :: ['human'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'tumour'] @entity19 :: ('10090', 'Species') :: ['transgenic mice'] @entity379 :: ('3458', 'Gene') :: ['IFN-gamma'] @entity3059 :: ('2315', 'Gene') :: ['MART-1'] @entity16051 :: ('246100', 'Gene') :: ['NY-ESO-1'] @entity6621 :: ('10245', 'Species') :: ['vaccinia virus']
@entity5 :: (MESH:D009369,Disease) :: ['tumour']
