Claims
- 1. A method of stimulating antibody dependent cellular cytotoxicity in a subject, comprising
administering an antibody and an agent selected from the group consisting of an imidazoquinoline agent and an C8-substituted guanosine to a subject in need of such treatment in an amount effective to stimulate antibody dependent cellular cytotoxicity in the subject.
- 2. The method of claim 1, wherein the agent is imidazoquinoline agent.
- 3. The method of claim 2, further comprising administering an C8-substituted guanosine to the subject.
- 4. The method of claim 2, further comprising administering a poly-arginine to the subject.
- 5. The method of claim 1, further comprising administering an immunostimulatory nucleic acid to the subject.
- 6. The method of claim 5, wherein the immunostimulatory nucleic acid is selected from the group consisting of a CpG nucleic acid and a poly-G nucleic acid.
- 7. The method of claim 5, wherein the immunostimulatory nucleic acid is selected from the group consisting of a poly-T nucleic acid, a T-rich nucleic acid, a TG nucleic acid, a CpI nucleic acid and a methylated CpG nucleic acid.
- 8. The method of claim 5, wherein the immunostimulatory nucleic acid has a backbone modification that is selected from the group consisting of a phosphorothioate modification and a peptide modification.
- 9. The method of claim 5, wherein the immunostimulatory nucleic acid has a backbone that is chimeric.
- 10. The method of claim 1, wherein the antibody is selected from the group consisting of an anti-cancer antibody, an anti-viral antibody, an anti-bacterial antibody, an anti-fungal antibody, an anti-allergen antibody, and an anti-self antigen antibody.
- 11. The method of claim 1, wherein the subject has or is at risk of having a disorder selected from the group consisting of asthma/allergy, infectious disease, cancer and warts.
- 12. The method of claim 1, wherein the imidazoquinoline agent is administered prior to the antibody.
- 13. The method of claim 1, wherein the imidazoquinoline agent is an imidazoquinoline amine.
- 14. The method of claim 1, wherein the imidazoquinoline agent is selected from the group consisting of imiquimod/R-837 and S-28463/R-848.
- 15. The method of claim 1, wherein the amount effective to stimulate antibody dependent cellular cytotoxicity is a synergistic amount.
- 16. A method for modulating an immune response in a subject, comprising
administering to a subject in need of such treatment an immunostimulatory nucleic acid and an agent selected from the group consisting of an imidazoquinoline agent and an C8-substituted guanosine in an amount effective to modulate the immune response.
- 17. The method of claim 16, wherein the agent is an imidazoquinoline agent.
- 18. The method of claim 17, further comprising administering an C8-substituted guanosine to the subject.
- 19. The method of claim 16, wherein the immune response is a Th1 immune response.
- 20. The method of claim 16, wherein the immune response is antibody dependent cellular cytotoxicity.
- 21. The method of claim 16, wherein the immune response is an innate immune response.
- 22. The method of claim 16, wherein the immunostimulatory nucleic acid is selected from the group consisting of a CpG nucleic acid and a poly-G nucleic acid.
- 23. The method of claim 16, wherein the immunostimulatory nucleic acid is selected from the group consisting of a poly-T nucleic acid, a T-rich nucleic acid, a TG nucleic acid, a CpI nucleic acid and a methylated CpG nucleic acid.
- 24. The method of claim 16, wherein the immunostimulatory nucleic acid has a backbone modification that is selected from the group consisting of a phosphorothioate modification and a peptide modification.
- 25. The method of claim 16, wherein the immunostimulatory nucleic acid has a chimeric backbone.
- 26. The method of claim 16, wherein the imidazoquinoline agent is an imidazoquinoline amine.
- 27. The method of claim 16, wherein the imidazoquinoline agent is selected from the group consisting of imiquimod/R-837 and S-28463/R-848.
- 28. The method of claim 16, wherein the immune response is a local immune response.
- 29. The method of claim 16, wherein the immune response is a mucosal immune response.
- 30. The method of claim 16, wherein the immune response is a systemic immune response.
- 31. The method of claim 16, wherein the agent is administered prior to the immunostimulatory nucleic acid.
- 32. The method of claim 16, wherein the amount effective to modulate the immune response is a synergistic amount.
- 33. The method of claim 16, further comprising administering poly-arginine to the subject.
- 34. The method of claim 16, further comprising administering an C8-substituted guanosine to the subject.
- 35. The method of claim 16, further comprising administering a disorder-specific medicament to the subject.
- 36. The method of claim 35, wherein the disorder-order specific medicament is selected from the group consisting of a cancer medicament, an asthma/allergy a medicament, an infectious disease medicament, and a wart medicament.
- 37. The method of claim 36, wherein the cancer medicament is selected from the group consisting of a chemotherapeutic agent, an immunotherapeutic agent and a cancer vaccine.
- 38. The method of claim 36, wherein the asthma/allergy medicament is selected from the group consisting of steroids, immunomodulators, anti-inflammatory agents, bronchodilators, leukotriene modifiers, β2 agonists, and anti-cholinergics.
- 39. The method of claim 36, wherein the anti-microbial medicament is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, and an anti-parasitic agent.
- 40. The method of claim 16, further comprising exposing the subject to an antigen and wherein the immune response is an antigen-specific immune response.
- 41. The method of claim 40, wherein the antigen is selected from the group consisting of a tumor antigen, a viral antigen, a bacterial antigen, a parasitic antigen, and a fungal antigen.
- 42. The method of claim 16, wherein the subject has or is at risk of developing an infectious disease.
- 43. The method of claim 16, wherein the subject has or is at risk of developing a cancer.
- 44. The method of claim 16, wherein the subject has or is at risk of developing asthma/allergy.
- 45. The method of claim 16, wherein the subject is an immunocompromised subject.
- 46. The method of claim 16, wherein the subject is elderly or an infant.
- 47. A composition, comprising
an imidazoquinoline agent, and an immunostimulatory nucleic acid.
- 48. The composition of claim 47, further comprising poly-arginine.
- 49. The composition of claim 47, further comprising an antigen.
- 50. The composition of claim 47, further comprising an C8-substituted guanosine.
- 51. The composition of claim 47, wherein the immunostimulatory nucleic acid is a CpG nucleic acid.
- 52. The composition of claim 51, wherein the immunostimulatory nucleic acid is a poly-G nucleic acid.
- 53. The composition of claim 47, wherein the immunostimulatory nucleic acid is a T-rich nucleic acid.
- 54. A composition comprising
an imidazoquinoline agent and an antibody.
- 55. The composition of claim 54, further comprising poly-arginine.
- 56. The composition of claim 55, further comprising an immunostimulatory nucleic acid.
- 57. The composition of claim 54, further comprising an C8-substituted guanosine.
- 58. A composition, comprising
an imidazoquinoline agent and a disorder-specific medicament.
- 59. The composition of claim 58, wherein the disorder-specific medicament is selected from the group consisting of an asthma/allergy medicament, a cancer medicament, and an anti-microbial medicament.
- 60. The composition of claim 58, further comprising poly-arginine.
- 61. The composition of claim 58, further comprising an immunostimulatory nucleic acid.
- 62. The composition of claim 58, further comprising an C8-substituted guanosine.
- 63. The composition of claim 59, wherein the asthma/allergy medicament is selected from the group consisting of steroids, immunomodulators, anti-inflammatory agents, bronchodilators, leukotriene modifiers, β2 agonists, and anti-cholinergics.
- 64. The composition of claim 59, wherein the cancer medicament is selected from the group consisting of a chemotherapeutic agent, an immunotherapeutic agent and a cancer vaccine.
- 65. The composition of claim 59, wherein the anti-microbial medicament is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, and an anti-parasitic agent.
- 66. A method for inducing an antigen-specific immune response in a subject comprising
administering to a subject an antigen, an imidazoquinoline agent, and an immunostimulatory nucleic acid in an effective amount to induce an antigen specific immune response.
- 67. The method of claim 66, wherein the antigen is selected from the group consisting of selected from the group consisting of a tumor antigen, a viral antigen, a bacterial antigen, a parasitic antigen, and a fungal antigen.
- 68. A screening method for comparing Toll-like receptor (TLR) signaling activity of a test compound with TLR signaling activity of an imidazoquinoline, comprising:
contacting a functional TLR selected from the group consisting of Toll-like receptor 7 (TLR7) and Toll-like receptor 8 (TLR8) with a reference imidazoquinoline and detecting a reference response mediated by a TLR signal transduction pathway; contacting a functional TLR selected from the group consisting of TLR7 and TLR8 with a test compound and detecting a test response mediated by a TLR signal transduction pathway; and comparing the test response with the reference response to compare the TLR signaling activity of the test compound with the imidazoquinoline.
- 69. The method of claim 68, wherein the functional TLR is TLR8.
- 70. The method of claim 68, wherein the functional TLR is TLR7.
- 71. The method of claim 68, wherein the functional TLR is contacted with the reference imidazoquinoline and the test compound independently.
- 72. The method of claim 71, wherein the screening method is a method for identifying an imidazoquinoline mimic, and wherein when the test response is similar to the reference response the test compound is an imidazoquinoline mimic.
- 73. The method of claim 68, wherein the functional TLR is contacted with the reference imidazoquinoline and the test compound concurrently to produce a test-reference response mediated by a TLR signal transduction pathway and wherein the test-reference response may be compared to the reference response.
- 74. The method of claim 73, wherein the screening method is a method for identifying an imidazoquinoline agonist, and wherein when the test-reference response is greater than the reference response the test compound is an imidazoquinoline agonist.
- 75. The method of claim 73, wherein the screening method is a method for identifying an imidazoquinoline antagonist, and wherein when the test-reference response is less than the reference response the test compound is an imidazoquinoline antagonist.
- 76. The method of claim 68, wherein the functional TLR is expressed in a cell.
- 77. The method of claim 76, wherein the cell is an isolated mammalian cell that naturally expresses functional TLR8.
- 78. The method of claim 77, wherein the cell comprises an expression vector comprising an isolated nucleic acid which encodes a reporter construct selected from the group consisting of interleukin 8 (IL-8), p40 subunit of interleukin 12 (IL-12 p40), nuclear factor kappa B-luciferase (NF-kappaB-luc), p40 subunit of interleukin 12-luciferase (IL-12 p40-luc), and tumor necrosis factor-luciferase (TNF-luc).
- 79. The method of claim 68, wherein the functional TLR is part of a cell-free system.
- 80. The method of claim 68, wherein the functional TLR is part of a complex with another TLR.
- 81. The method of claim 68, wherein the functional TLR is part of a complex with a non-TLR protein selected from the group consisting of myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase (IRAK), tumor necrosis factor receptor-associated factor 6 (TRAF6), IkappaB, NF-kappaB, and functional homologs and derivatives thereof.
- 82. The method of claim 68, wherein the reference imidazoquinoline is R-848 (Resiquimod).
- 83. The method of claim 68, wherein the reference imidazoquinoline is R-847 (Imiquimod).
- 84. The method of claim 68, wherein the test compound is not a nucleic acid molecule.
- 85. The method of claim 68, wherein the test compound is a polypeptide.
- 86. The method of claim 68, wherein the test compound is an imidazoquinoline other than R-848 or R-847.
- 87. The method of claim 68, wherein the test compound is a part of a combinatorial library of compounds.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent Application filed Oct. 12, 2001 entitled “METHODS AND PRODUCTS FOR ENHANCING IMMUNE RESPONSES USING IMIDAZOQUINOLINE COMPOUNDS”, Serial No. 60/329,208, the contents of which are incorporated by reference herein in their entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60329208 |
Oct 2001 |
US |