Nucleic acid compositions for stimulating immune responses
View Patent ↗The invention provides an immunostimulatory nucleic acid comprising CpG motifs, and methods of use thereof in stimulating immunity.
1. A composition comprising
an immunostimulatory nucleic acid comprising the nucleotide sequence of SEQ ID NO: 1, wherein the immunostimulatory nucleic acid has a nucleotide backbone comprising at least one phosphorothioate modification.
2. The composition of claim 1 , wherein the immunostimulatory nucleic acid consists of the nucleotide sequence of SEQ ID NO: 1.
3. The composition of claim 1 , further comprising an antigen, wherein the antigen is not a nucleic acid vector encoding the antigen.
4. The composition of claim 3 , wherein the antigen is selected from the group consisting of a microbial antigen, a cancer antigen, and an allergen.
5. The composition of claim 4 , wherein the microbial antigen is selected from the group consisting of a bacterial antigen, a viral antigen, a fungal antigen and a parasitic antigen.
6. The composition of claim 3 , wherein the antigen is a peptide antigen.
7. The composition of claim 1 , further comprising an adjuvant.
8. The composition of claim 7 , wherein the adjuvant is a mucosal adjuvant.
9. The composition of claim 1 , further comprising a cytokine.
10. The composition of claim 1 , further comprising a therapeutic agent selected from the group consisting of an anti-microbial agent, an anti-cancer agent, and an allergy/asthma medicament.
11. The composition of claim 10 , wherein the anti-microbial agent is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, and an anti-parasite agent.
12. The composition of claim 10 , wherein the anti-cancer agent is selected from the group consisting of a chemotherapeutic agent, a cancer vaccine, and an immunotherapeutic agent.
13. The composition of claim 10 , wherein the allergy/asthma medicament is selected from the group consisting of PDE-4 inhibitor, bronchodilator/beta-2 agonist, K+channel opener, VLA-4 antagonist, neurokin antagonist, TXA2 synthesis inhibitor, xanthanine, arachidonic acid antagonist, 5 lipoxygenase inhibitor, thromboxin A2 receptor antagonist, thromboxane A2 antagonist, inhibitor of 5-lipox activation protein, and protease inhibitor.
14. The composition of claim 1 , wherein the nucleotide backbone is chimeric.
15. The composition of claim 1 , wherein the nucleotide backbone is entirely modified.
16. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
17. The composition of claim 1 , wherein the immunostimulatory nucleic acid is formulated as a nutritional supplement.
18. The composition of claim 17 , wherein the nutritional supplement is formulated as a capsule, a pill, or a sublingual tablet.
19. The composition of claim 1 , wherein the immunostimulatory nucleic acid is formulated for local administration.
20. The composition of claim 1 , wherein the immunostimulatory nucleic acid is formulated for parenteral administration.
21. The composition of claim 1 , wherein the immunostimulatory nucleic acid is formulated in a sustained release device.
22. The composition of claim 1 , wherein the immunostimulatory nucleic acid is formulated for delivery to a mucosal surface.
23. The composition of claim 21 , wherein the sustained release device is a microparticle.
24. A method for stimulating an immune response in a subject in need thereof comprising
administering to a subject the immunostimulatory nucleic acid of claim 1 , in an amount effective to stimulate an immune response, wherein the subject has or is at risk of developing a cancer.
25. The method of claim 24 , wherein the subject has or is at risk of developing an infection.
26. The method of claim 24 , further comprising administering an antigen to the subject.
27. The method of claim 26 , wherein the antigen is selected from the group consisting of a microbial antigen, a cancer antigen, and a self antigen.
28. The method of claim 24 , wherein the immune response is an antigen-specific immune response.
29. The method of claim 24 , further comprising administering to the subject a second therapeutic agent.
30. The method of claim 24 , wherein the immunostimulatory nucleic acid has a nucleotide backbone that is chimeric.
31. The method of claim 24 , wherein the immunostimulatory nucleic acid has a nucleotide backbone that is entirely modified.
32. The method of claim 24 , wherein the immunostimulatory nucleic acid is administered orally.
33. The method of claim 24 , wherein the immunostimulatory nucleic acid is administered locally.
34. The method of claim 24 , wherein the immunostimulatory nucleic acid is administered parenterally.
35. The method of claim 24 , wherein the immunostimulatory nucleic acid is administered in a sustained release device.
36. The method of claim 24 , wherein the immunostimulatory nucleic acid is administered to a mucosal surface.
37. The method of claim 36 , wherein the mucosal surface is selected from the group consisting of an oral, nasal, rectal, vaginal, and ocular surface.
38. The method of claim 24 , further comprising isolating an immune cell from the subject, contacting the immune cell with an effective amount to activate the immune cell of the immunostimulatory nucleic acid and re-administering the activated immune cell to the subject.
39. The method of claim 24 , wherein the subject is a human.
40. The method of claim 24 , wherein the subject is selected from the group consisting of a dog, cat, horse, cow, pig, sheep, goat, chicken, monkey and fish.
41. The method of claim 24 , wherein the cancer is selected from the group consisting of biliary tract cancer; bone cancer; brain and CNS cancer; breast cancer; cervical cancer; choriocarcinoma; colon cancer; connective tissue cancer; endometrial cancer; esophageal cancer; eye cancer; gastric cancer; Hodgkin's lymphoma; intraepithelial neoplasms; larynx cancer; lymphomas; liver cancer; lung cancer; melanoma; neuroblastomas; oral cavity cancer; ovarian cancer; pancreas cancer; prostate cancer; rectal cancer; sarcomas; skin cancer; testicular cancer; thyroid cancer; and renal cancer.
42. The method of claim 24 , further comprising administering an antibody specific for a cell surface antigen, and wherein the immune response results in antibody dependent cellular cytotoxicity (ADCC).
43. A method for inducing an innate immune response, comprising
administering to the subject the immunostimulatory nucleic acid of claim 1 in an amount effective for activating an innate immune response.
44. A composition comprising
an immunostimulatory nucleic acid comprising the nucleotide sequence of SEQ ID NO: 1, wherein the immunostimulatory nucleic acid is 24-100 nucleotides in length and comprises a CpG motif that is unmethylated.
45. A composition comprising
an immunostimulatory nucleic acid comprising the nucleotide sequence of SEQ ID NO: 1, and an antigen, wherein the antigen is not a nucleic acid vector encoding the antigen.
46. The composition of claim 44 , wherein the immunostimulatory nucleic acid is single stranded.
47. The composition of claim 44 , wherein the immunostimulatory nucleic acid consists of the nucleotide sequence of SEQ ID NO: 1.
48. The composition of claim 44 , wherein the immunostimulatory nucleic acid has a nucleotide backbone comprising at least one modification.
49. The composition of claim 44 , further comprising an antigen, wherein the antigen is not a nucleic acid vector encoding the antigen.
50. The method of claim 41 , wherein the lung cancer is small cell lung cancer.
51. The method of claim 41 , wherein the lung cancer is non-small cell lung cancer.
52. The composition of claim 44 , wherein the immunostimulatory nucleic acid has a nucleotide backbone comprising at least one phosphorothioate modification.