Abstract
Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen-loading of dendritic cells (DC) generates significant and rapid (one stimulation/one week) cytotoxic T lymphocyte (CTL) responses in vitro against viral and self antigens. To further improve this already potent technique we compared co-infection of an AAV/antigen vector, AAV/HPV-E6/Neo, with a rAAV vector carrying one of four cytokines. These included interleukin (IL)-2, interferon (IFN) gamma, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-7. Previously we have shown that the delivery of the GM-CSF gene into DC resulted in secretion of this transgene cytokine. Furthermore the freshly secreted cytokine had a 100–1000 fold higher biological activity on a per weight basis compared to recombinant commercial exogenously added cytokine. Here, in a head-to-head comparison the delivery of the IL-7 gene appeared superior to IL-2 and IFN-gamma for improving CTL response. In a second comparison the infection of DC by IL-7 was compared to the direct infection of T cells. In a head-to-head comparison the direct delivery/infection of IL-7 into the T cell population generated significantly higher levels of killing of E7-positive target cells. These data suggest that the use of cytokine genes can improve CTL response and also suggests that a number of further procedural improvements can be made.
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