ABSTRACT
The invention involves the discovery that if dendritic cells loaded with a tumor antigen are cultured in interleukin-15 (IL-15), or if T cells activated by the dendritic cells are cultured in IL-15, Treg activity that is specific for the tumor antigen is reduced. This reduction in Treg activity results in an increase in anti-tumor immune response. Another embodiment of the invention involves the discovery that incubating dendritic cells with a MAP kinase inhibitor in combination with IL-15 gives synergistic benefits when the dendritic cells are used to activate T cells. Dendritic cell and T cell compositions incubated with IL-15 or a MAP kinase inhibitor are provided.
CLAIMS
1. A therapeutic composition comprising: dendritic cells prepared by culturing adherent PBMC dendritic cell precursors ex vivo in the presence of GM-CSF, IL-4, IL-15 and a p38 MAP kinase inhibitor in amounts and for a time effective to differentiate said precursors into dendritic cells that function to reduce Treg activity and Foxp3 expression and increase TNF-alpha expression and CCR4 expression in T cells contacted with the dendritic cells, and loading the dendritic cells with an antigen ex vivo.