Methods of treating cancer using immunostimulatory oligonucleotides
View Patent ↗Nucleic acid sequences containing unmethylated CpG dinucleotides that modulate an immune response including stimulating a Th1 pattern of immune activation, cytokine production, NK lytic activity, and B cell proliferation are disclosed. The sequences are also useful as a synthetic adjuvant.
1. A method for treating cancer, comprising:
administering to a human subject an effective amount for treating cancer of a CpG immunostimulatory oligonucleotide having at least one unmethylated CpG dinucleotide, wherein at least one nucleotide of the stabilized CpG immunostimulatory oligonucleotide has a phosphate backbone modification and wherein the oligonucleotide is 8 to 100 nucleotides in length, wherein the phosphate backbone modification is a phosphorothioate modification, further comprising administering an antigen.
2. The method of claim 1 , further comprising administering a chemotherapeutic agent.
3. The method of claim 1 , further comprising administering a cancer immunotherapeutic agent.
4. The method of claim 1 , wherein the cancer is brain cancer.
5. The method of claim 1 , wherein the cancer is lung cancer.
6. The method of claim 1 , wherein the cancer is ovarian cancer.
7. The method of claim 1 , wherein the cancer is breast cancer.
8. The method of claim 1 , wherein the cancer is prostate cancer.
9. The method of claim 1 , wherein the cancer is colon cancer.
10. The method of claim 1 , wherein the cancer is leukemia.
11. The method of claim 1 , wherein the cancer is carcinoma.
12. The method of claim 1 , wherein the cancer is sarcoma.
13. The method of claim 1 , wherein the CpG immunostimulatory oligonucleotide comprises:
5′X 1 X 2 CGX 3 X 4 3′
wherein X 1 X 2 and X 3 X 4 are nucleotides.
14. The method of claim 13 , wherein X 3 X 4 are nucleotides selected from the group consisting of: TpT, and TpC.
15. The method of claim 13 , wherein X 1 X 2 are GpA and X 3 X 4 are TpT.
16. The method of claim 13 , wherein X 1 X 2 are both purines and X 3 X 4 are both pyrimidines.
17. The method of claim 13 , wherein X 1 X 2 are GpA and X 3 X 4 are both pyrimidines.
18. The method of claim 13 , wherein the oligonucleotide is 8 to 40 nucleotides in length.
19. The method of claim 13 , wherein 5′ X 1 X 2 CGX 3 X 4 3′ is not palindromic.
20. The method of claim 1 , wherein the CpG immunostimulatory oligonucleotide includes at least two CpG motifs.
21. The method of claim 20 , wherein at least one of the at least two CpG motifs is not palindromic.
22. The method of claim 1 , wherein the oligonucleotide is administered prior to a chemotherapy.
23. The method of claim 1 , wherein the oligonucleotide is administered subcutaneously.
24. A method for treating non small cell lung carcinoma (NSCLC) in a human subject, comprising
administering to a human subject having NSCLC an effective amount to treat NSCLC of an immunostimulatory oligonucleotide that includes at least one unmethylated CpG dinucleotide, wherein the immunostimulatory oligonucleotide includes a phosphate backbone modification and, wherein the oligonucleotide is 8 to 100 nucleotides in length, wherein the phosphate backbone modification is a phosphorothioate modification, further comprising administering an antigen.
25. The method of claim 24 , further comprising administering a chemotherapeutic agent.
26. The method of claim 24 , further comprising administering an immunotherapeutic agent.
27. The method of claim 24 , wherein the oligonucleotide is 8 to 40 nucleotides in length.
28. The method of claim 24 , wherein the CpG immunostimulatory oligonucleotide includes at least two CpG motifs.
29. The method of claim 28 , wherein at least one of the at least two CpG motifs is not palindromic.
30. The method of claim 24 , wherein the oligonucleotide is administered subcutaneously.