Continuous cell programming devices
The present invention comprises compositions, methods and devices for creating an infection-mimicking environment within a polymer scaffold to stimulate antigen-specific dendritic cell activation. Devices of the present invention are used to provide protective immunity to subjects against infection and cancer.
1. A method of continuous in situ dendritic cell programming, comprising administering to a subject a device comprising
a scaffold polymer selected from the group consisting of poly-lactide-co-glycolide (PLG), alginate, xantham gum, gellan, or emulsan;
a tumor antigen;
a recruitment composition comprising a cytokine, which comprises a granulocyte macrophage colony stimulating factor (GM-CSF) that recruits one or more dendritic cells to temporarily reside within said device; and
a positively charged polyethylenimine (PEI)-condensed toll-like receptor-9 (TLR-9)-activating CpG-ODN which is retained in or on said scaffold polymer,
wherein said device attracts a dendritic cell and enhances uptake of said CpG-ODN into said dendritic cell, thereby continuously stimulating said dendritic cell to induce an immune response, and wherein said PEI condensed CpG-ODN overcomes the trapping effect of the cytokine on said dendritic cell, thereby inducing said dendritic cell to migrate away from said device.
2. The method of claim 1 , wherein said tumor antigen comprises a biopsy tumor cell lysate.
3. The method of claim 1 , wherein said device is administered locally at or near a tumor site.
4. The method of claim 1 , wherein said dendritic cell comprises a plasmacytoid dendritic cell.
5. The method of claim 1 , wherein the scaffold polymer is alginate.
6. The method of claim 1 , wherein the scaffold polymer is PLG.
7. The method of claim 1 , wherein the CpG-ODN is CpG-ODN 1826.
8. The method of claim 1 , wherein the PEI-CpG-ODN is retained in said scaffold polymer.