Method of eliciting an anti-tumor immune response with controlled delivery of TLR agonists in porous polymerlc devices
The present invention comprises compositions, methods, and devices for creating an stimulating an antigen-specific dendritic cell immune response. Devices and methods provide prophylactic and therapeutic immunity to subjects against cancer and infectious agents.
1. A device comprising a porous polymeric structure composition, and a toll-like receptor 3 (TLR3) agonist, wherein said TLR3 is in an amount effective to activate an antigen presenting cell.
2. The device of claim 1 , further comprising a tumor antigen.
3. The device of claim 1 , wherein said polymeric structure composition comprises poly-lactide-co-glycolide (PLG).
4. The device of claim 1 , wherein said TLR3 agonist comprises polyinosine-polycytidylic acid (poly I:C) or PEI- poly (I:C).
5. The device of claim 1 , further comprising pathogen associated molecular patterns (PAMPs).
6. The device of claim 1 , wherein said TLR3 agonist comprises a nucleic acid.
7. The device of claim 1 , further comprising a TLR9 agonist.
8. The device of claim 7 , wherein said TLR9 agonist comprises a cytosine-guanosine oligonucleotide (CpG-ODN) or a PEI-CpG-ODN.
9. The device of claim 1 , wherein said device further comprises a cytokine capable of recruiting an antigen presenting cell into the porous polymeric structure composition.
10. The device of claim 9 , wherein said cytokine comprises granulocyte macrophage colony stimulating factor (GM-CSF), Flt3L, or CCL20.
11. The device of claim 9 , wherein said cytokine comprises encapsulated GM-CSF.
12. The device of claim 2 , wherein said tumor antigen comprises a tumor lysate, purified protein tumor antigen, or synthesized tumor antigen.
13. The device of claim 5 , wherein said PAMPs comprises a monophosphoryl lipid A (MPLA).
14. The device of claim 7 , wherein said TLR3 agonist comprises poly (I:C) and said TLR9 agonist comprises CpG-ODN.
15. The device of claim 1 , further comprising a TLR4 agonist.
16. The device of claim 15 , wherein said TLR3 agonist comprises poly (I:C) and said TLR4 agonist comprises MPLA.
17. The device of claim 1 , wherein said TLR3 agonist is present in an amount to preferentially stimulate CD8+ dendritic cells or CD141+ dendritic cells.
18. A device comprising a polymeric structure composition, a toll-like receptor 3 (TLR3) agonist, and a second toll-like receptor (TLR) agonist selected from the group consisting of TLR1, TLR2, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13.
19. A method for eliciting an anti-tumor immune response, comprising contacting or implanting into a subject a device comprising a polymeric structure composition, and a toll-like receptor 3 (TLR3) agonist, wherein said TLR3 agonist is in an amount effective to activate an antigen presenting cell.
20. The method of claim 19 , wherein said device further comprises a tumor antigen.
21. The method of claim 19 , wherein said device further comprises a TLR9 agonist.
22. The method of claim 19 , wherein said anti-tumor immune response comprises activation of a CD8+ dendritic cell or a CD141+ dendritic cell.
23. The method of claim 21 , wherein said anti-tumor immune response comprises activation of a plasmacytoid dendritic cell or a CD141+ dendritic cell.
24. The method of claim 20 , wherein said anti-tumor immune response comprises a reduction in tumor burden.
25. The method of claim 19 , wherein said TLR3 agonist is present at a concentration effective to induce production of interleukin-12 (IL-12) by dendritic cells.
26. The device of claim 1 , wherein said antigen presenting cell is a dendritic cell.
27. The method of claim 19 , wherein said antigen presenting cell is a dendritic cell.