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. A method of modulating an immune response in a mammal comprising: administering to a mammal an immunomodulatory polynucleotide (IMP) in an amount sufficient to modulate an immune response in said-mammal, wherein said IMP comprises:
(SEQ ID NO: 156)
a) 5′-N x (TCG(N q )) y N w (X 1 X 2 CGX 2 ′X 1 ′CG) p ) z
wherein N are nucleosides, x=0-3, y=1-4, w=−2, −1, 0, 1 or 2, p=0 or 1, q=0, 1 or 2, and z=1-20, X 1 and X 1 ′ are self-complimentary nucleosides, X 2 and X 2 ′ are self-complimentary nucleosides, and wherein the 5′ T of the (TCG(N q )) y sequence is 0-3 bases from the 5′ end of the polynucleotide; and
b) a palindromic sequence at least 8 bases in length wherein the palindromic sequence comprises the first (X 1 X 2 CGX 2 ′X 1 ′) of the (X 1 X 2 CGX 2 ′X 1 ′(CG) p ) z sequences, and wherein the mammal has cancer.
2. The method of to claim 1 wherein the IMP comprises a sequence selected from the group consisting of SEQ ID NO: 172, SEQ ID NO: 55, SEQ ID NO: 113, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 53, SEQ ID NO: 109, SEQ ID NO: 117, SEQ ID NO: 175, SEQ ID NO: 45, SEQ ID NO: 75, and SEQ ID NO: 44.
3. The method of claim 1 wherein the mammal is receiving a vaccine.
4. The method of claim 3 wherein the vaccine is a prophylactic vaccine.
5. The method of claim 3 wherein the vaccine is a therapeutic vaccine.
6. The method of claim 5 wherein the therapeutic vaccine comprises tumor associated antigens and/or tumor cells from a mammal with cancer.
7. The method of claim 1 wherein the method further comprises administration of one or more additional therapeutic agents.
8. The method of claim 7 wherein the one or more additional therapeutic agents is selected from the group consisting of: anti-tumor antibodies, chemotherapy regimens and radiation treatments.
9. The method of claim 8 wherein the anti-tumor antibodies are anti-tumor antibody fragments and/or derivatives thereof or monoclonal anti-tumor antibodies, fragments and/or derivatives thereof.
10. The method of claim 8 wherein the anti-tumor antibodies are rituximab or trastuzumab.
11. The method of claim 7 wherein therapeutic agent is an immunotherapeutic agent selected from the group consisting of cytokines, adjuvants, and antibodies.
12. The method of claim 1 , wherein the IMP comprises SEQ ID NO: 172.
13. The method of any one of claims 1 , 2 and 3 - 12 , wherein the mammal is a human.