Stimulation of an immune response by cationic lipids
The present invention provides compositions and methods for stimulating an immune response using cationic lipids alone or in combination with antigens.
1. A pharmaceutical formulation comprising a liposome together with at least one disease-associated antigen and a non-ionic buffer, wherein the liposome comprises one or more cationic lipids,
wherein the one or more cationic lipid consists of a quaternary cationic lipid, and
wherein the pharmaceutical formulation is free of phosphate buffered saline (PBS); and
wherein the disease-associated antigen is a protein or peptide.
2. The pharmaceutical formulation of claim 1 , wherein the one or more cationic lipids consists of non-steroidal cationic lipids.
3. The pharmaceutical formulation of claim 1 , wherein the one or more cationic lipids is DOTAP, DMTAP, DSTAP, DPTAP, DPEPC, DSEPC, DMEPC, DLEPC, DOEPC, DMKE, DMKD, or DOSPA, and combinations thereof.
4. The pharmaceutical formulation of claim 1 , wherein the disease-associated antigen is a pathogen-associated antigen.
5. The pharmaceutical formulation of claim 4 , wherein the disease-associated antigen is an HPV antigen.
6. A pharmaceutical formulation comprising: a liposome and at least one disease-associated antigen and a non-ionic buffer,
wherein the liposome comprises one or more cationic lipids,
wherein the at least one disease-associated antigen consists of at least one tumor-associated antigen, wherein the disease-associated antigen is a protein or peptide,
wherein the one or more cationic lipids consists of a quaternary cationic lipid,
wherein the one or more cationic lipids is in an amount sufficient to both activate the ERK or p38 components of the MAP kinase signaling pathway and to induce the production of reactive oxygen species by at least 1.2-fold but less than 20-fold over baseline levels, and
wherein the pharmaceutical formulation is free of phosphate buffered saline (PBS).
7. The pharmaceutical formulation of claim 6 , wherein the one or more cationic lipids is a non-steroidal cationic lipid.
8. The pharmaceutical formulation of claim 6 , wherein the one or more cationic lipids is DOTAP, DMTAP, DSTAP, DPTAP, DPEPC, DSEPC, DMEPC, DLEPC, DOEPC, DMKE, DMKD, or DOSPA, and combinations thereof.
9. The pharmaceutical formulation of claim 6 , wherein the tumor-associated antigen is a pathogen-associated antigen.
10. The pharmaceutical formulation of claim 6 , wherein the tumor-associated antigen is an HPV antigen.
11. A cationic lipid complex comprising a liposome, together with at least one tumor-associated antigen and a non-ionic buffer,
wherein the liposome comprises one or more cationic lipids,
wherein the one or more cationic lipids consists of a quaternary cationic lipid,
wherein the one or more cationic lipids is in an amount sufficient to induce cytokine and chemokine production in a mammal above the level of cytokine and chemokine production present in the absence of the cationic lipid complex,
wherein the cationic lipid is in an amount sufficient to both activate the ERK or p38 components of the MAP kinase signaling pathway and to induces the production of reactive oxygen species by at least 1.2-fold but less than 20-fold over baseline levels,
and wherein the cationic lipid complex is free of phosphate buffered saline (PBS); and
wherein the disease-associated antigen is a protein or peptide.
12. The cationic lipid complex of claim 11 , wherein the one or more cationic lipids is a non-steroidal lipid.
13. The cationic lipid complex of claim 11 , wherein the one or more cationic lipids is DOTAP, DMTAP, DSTAP, DPTAP, DPEPC, DSEPC, DMEPC, DLEPC, DOEPC, DMKE, DMKD, or DO SPA and combinations thereof.
14. The cationic lipid complex of claim 11 , wherein the cytokine and chemokine production includes production of one or more of TNF-α, IL-12, CCL3, CCL4, CCL5, and CCL-19.
15. A pharmaceutical formulation comprising a liposome together with at least one disease-associated antigen and a non-ionic buffer,
wherein the liposome comprises one or more cationic lipids,
wherein the one or more cationic lipids is a quaternary cationic lipid,
wherein the one or more cationic lipids is in an amount sufficient to both activate the ERK or p38 components of the MAP kinase signaling pathway and to induce the production of reactive oxygen species by at least 10% of immune cells in the lymph nodes, and
wherein the pharmaceutical formulation is free of phosphate buffered saline (PBS);
wherein the disease-associated antigen is a protein or peptide.
16. The pharmaceutical formulation of claim 15 , wherein the one or more cationic lipids consists of non-steroidal cationic lipids.
17. The pharmaceutical formulation of claim 15 , wherein the one or more cationic lipids is DOTAP, DMTAP, DSTAP, DPTAP, DPEPC, DSEPC, DMEPC, DLEPC, DOEPC, DMKE, DMKD, or DOSPA, and combinations thereof.
18. The pharmaceutical formulation of claim 15 , wherein the disease associated antigen is an HPV antigen.
19. The pharmaceutical formulation of claim 1 , wherein the non-ionic buffer is water.
20. The pharmaceutical formulation of claim 1 , further comprising a pharmaceutical carrier.
21. The pharmaceutical formulation of claim 20 , wherein the pharmaceutical carrier is sugar.