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 method of treating a disease or infection in a mammal, the method comprising administering at least one cationic lipid together with at least one tumor-associated antigen or naturally-occurring microbial antigen, wherein the cationic lipid is administered to the mammal in an amount sufficient to activate the MAP kinase signaling pathway to elicit an immunostimulatory adjuvant effect,
wherein a mouse dose of cationic lipid is between 10 nmol and about 400 nmol,
and wherein the mammal dose of cationic lipid is determined from the mouse dose.
2. The method of claim 1 wherein the cationic lipid is a nonsteroidal cationic lipid comprising at least one fatty acid or alkyl chain.
3. The method of claim 1 wherein the cationic lipid is selected from the group consisting of DOTAP, DOTMA, DOEPC, and combinations thereof.
4. The method of claim 1 wherein the cationic lipid is DOTAP.
5. The method of claim 1 wherein the disease is cancer.
6. The method of claim 1 wherein the antigen is modified to increase its hydrophobicity, wherein the antigen is modified via conjugation to a lipid chain or via conjugation to one or more hydrophobic amino acids.
7. The method of claim 6 wherein the antigen is a lipidated antigen.
8. The method of claim 7 wherein the antigen is lipidated with palmitic acid.
9. The method of claim 8 wherein the palmitic acid is linked to the antigen via a spacer, wherein the spacer is an amino acid sequence of K-S-S.
10. A method of reducing the regulatory T-cell population in a mammal in need thereof, the method comprising administering to the mammal at least one cationic lipid and at least one tumor-associated antigen or naturally-occurring microbial antigen,
wherein a mouse dose of cationic lipid is between 10 nmol and about 400 nmol,
and wherein the mammal dose of cationic lipid is determined from the mouse dose.
11. The method of claim 10 wherein the cationic lipid is a nonsteroidal cationic lipid comprising at least one fatty acid or alkyl chain.
12. The method of claim 10 wherein the cationic lipid is selected from the group consisting of DOTAP, DOTMA, DOEPC, and combinations thereof.
13. The method of claim 10 wherein the cationic lipid is DOTAP.
14. A method of using a cationic lipid to elicit an immunostimulatory adjuvant effect in an immune system of a mammal, wherein the cationic lipid is administered with at least one tumor-associated antigen or naturally-occurring microbial antigen to the mammal in an amount sufficient to activate the MAP kinase signaling pathway to elicit the immunostimulatory adjuvant effect,
wherein a mouse dose of cationic lipid is between 10 nmol and about 400 nmol,
and wherein the mammal dose of cationic lipid is determined from the mouse dose.
15. The method of claim 14 wherein the cationic lipid is a nonsteroidal cationic lipid comprising at least one fatty acid or alkyl chain.
16. The method of claim 14 wherein the cationic lipid is selected from the group consisting of DOTAP, DOTMA, DOEPC, and combinations thereof.
17. The method of claim 14 wherein the cationic lipid is DOTAP.
18. The method of claim 1 wherein the amount of cationic lipid is between about 30 nmol and about 300 nmol.
19. The method of claim 10 wherein the amount of cationic lipid is between about 30 nmol and about 300 nmol.
20. The method of claim 14 wherein the amount of cationic lipid is between about 30 nmol and about 300 nmol.
21. A method of inducing an antibody response against an antigen in a mammal, the method comprising administering at least one cationic lipid together with at least one tumor-associated antigen or naturally-occurring microbial antigen, wherein the cationic lipid is administered to the mammal in an amount sufficient to induce the antibody response in response against the antigen,
wherein a mouse dose of cationic lipid is between 10 nmol and about 400 nmol,
and wherein the mammal dose of cationic lipid is determined from the mouse dose.
22. The method of claim 21 wherein the cationic lipid is a nonsteroidal cationic lipid comprising at least one fatty acid or alkyl chain.
23. The method of claim 21 wherein the cationic lipid is selected from the group consisting of DOTAP, DOTMA, DOEPC, and combinations thereof.
24. The method of claim 21 wherein the cationic lipid is DOTAP.
25. The method of claim 21 wherein the antigen is modified to increase its hydrophobicity, wherein the antigen is modified via conjugation to a lipid chain or via conjugation to one or more hydrophobic amino acids.
26. The method of claim 25 wherein the antigen is a lipidated antigen, and wherein the lipidated antigen is lipidated with palmitic acid.
27. The method of claim 26 wherein the palmitic acid is linked to the antigen via a spacer, wherein the spacer is an amino acid sequence of K-S-S.
28. The method of claim 21 wherein the amount of cationic lipid is between about 30 nmol and about 300 nmol.
29. The method of claim 1 , wherein the mammal is a human.
30. The method of claim 1 , wherein the mammal is a non-human.
31. The method of claim 1 , wherein the mouse dose of cationic lipid is between 0.05 nmol per microliter (μL) to about 3 nmol per μL.
32. The method of claim 1 , wherein the mouse dose of cationic lipid is between 0.05 mg per milliliter (mL) to about 2 mg per mL.
33. The method of claim 10 , wherein the mammal is a human.
34. The method of claim 10 , wherein the mammal is a non-human.
35. The method of claim 10 , wherein the mouse dose of cationic lipid is between 0.05 nmol per microliter (μL) to about 3 nmol per μL.
36. The method of claim 10 , wherein the mouse dose of cationic lipid is between 0.05 mg per milliliter (mL) to about 2 mg per mL.
37. The method of claim 14 , wherein the mammal is a human.
38. The method of claim 14 , wherein the mammal is a non-human.
39. The method of claim 14 , wherein the mouse dose of cationic lipid is between 0.05 nmol per microliter (μL) to about 3 nmol per μL.
40. The method of claim 14 , wherein the mouse dose of cationic lipid is between 0.05 mg per milliliter (mL) to about 2 mg per mL.
41. The method of claim 21 , wherein the mammal is a human.
42. The method of claim 21 , wherein the mammal is a non-human.
43. The method of claim 21 , wherein the mouse dose of cationic lipid is between 0.05 nmol per microliter (μL) to about 3 nmol per μL.
44. The method of claim 21 , wherein the mouse dose of cationic lipid is between 0.05 mg per milliliter (mL) to about 2 mg per mL.