Immunostimulatory sequence oligonucleotides and methods of using the same
The invention provides immunomodulatory polynucleotides and methods for immunomodulation of individuals using the immunomodulatory polynucleotides.
1. An immunomodulatory polynucleotide, consisting of the sequence of SEQ ID NO:117 or SEQ ID NO:174, wherein the polynucleotide comprises at least one phosphorothioate linkage.
2. The immunomodulatory polynucleotide according to claim 1 wherein the polynucleotide consists of the sequence of SEQ ID NO:117.
3. The immunomodulatory polynucleotide according to claim 1 wherein the polynucleotide consists of the sequence of SEQ ID NO:174.
4. The immunomodulatory polynucleotide according to claim 2 or claim 3 , wherein all nucleotide linkages are phosphorothioate linkages.
5. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the immunomodulatory polynucleotide of claim 4 .
6. A method of modulating an immune response in a human comprising: administering the pharmaceutical composition of claim 5 to the human in an amount sufficient to modulate an immune response in the human.
7. A method of increasing interferon-gamma (IFN-γ) in a human, comprising: administering the pharmaceutical composition of claim 5 to the human in an amount sufficient to increase IFN-γin the human.
8. A method of increasing interferon-alpha (IFN-α) in a human, comprising: administering the pharmaceutical composition of claim 5 to the human in an amount sufficient to increase IFN-αin the human.
9. The method of claim 6 , wherein the human is receiving a prophylactic vaccine or a therapeutic vaccine.
10. The method of claim 9 , wherein the therapeutic vaccine comprises tumor associated antigens and/or tumor cells.
11. The method of claim 6 , wherein the method further comprises administration of one or more additional therapeutic agents.
12. The method of claim 11 , wherein the one or more additional therapeutic agents comprise an anti-tumor antibody, and the anti-tumor antibody is a monoclonal anti-tumor antibody, fragment, or derivative thereof.
13. The method of claim 11 , wherein the one or more additional therapeutic agents comprise an immunotherapeutic agent selected from the group consisting of cytokines, adjuvants and antibodies.
14. The method of claim 11 , wherein the one or more additional therapeutic agents is selected from the group consisting of anti-tumor antibodies, chemotherapy regimens and radiation treatments.
15. The method of claim 14 , wherein the anti-tumor antibodies comprise rituximab or trastuzumab.
16. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the immunomodulatory polynucleotide of claim 2 .
17. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the immunomodulatory polynucleotide of claim 3 .