Synergistic stimulation of the immune system using immunostimulatory oligonucleotides and/or immunomer compounds in conjunction with cytokines and/or chemotherapeutic agents or radiation therapy
The invention provides optimized methods and compositions for enhancing the immune response caused by immunostimulatory compounds used for the treatment of disease such as, but not limited to, treatment of cancer, autoimmune disorders, asthma, respiratory allergies, food allergies and infectious diseases in a patient. The optimized methods according to the invention provide synergy between the therapeutic effects of immunostimulatory oligonucleotides and immunomer compounds in accordance with the invention, and the therapeutic effect of cytokine immunotherapy and/or chemotherapeutic agents and/or radiation.
1 . A method for treating cancer in a mammal comprising administering to a mammal having a tumor an immunostimulatory oligonucleotide or an immunomer compound and treating the animal with ionizing radiation.
2 . The method according to claim 1 , wherein γ-irradiation is administered at 1.56 Gy/min.
3 . The method according to claim 1 , wherein radiation therapy is administered as 3 Gy of radiation either twice for one week, four times for one week, or three times on Days 2, 4, and 9.
4 . The method of claim 1 , wherein the mammal is pre-treated with an immunostimulatory oligonucleotide or an immunomer compound from about 2 to about 6 h prior to γ-irradiation.
5 . A method for stimulating an immune response in a patient comprising administering to the patient a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory oligonucleotide and a therapeutically effective synergistic amount of IL-2.
6 . A method for stimulating an immune response in a patient comprising administering to the patient a combination of a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory nucleotide and a therapeutically effective synergistic amount of IL-2, wherein administration of said combination synergistically stimulates the production of cytokines.
7 . A method for stimulating an immune response in a patient comprising administering to the patient a combination of a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory oligonucleotide and a therapeutically effective synergistic amount of IL-2, wherein administration of said combination synergistically stimulates the production of one or more cytokines selected from the group consisting of IL-12 and IFN-γ, IFN-α, IFN-β or combinations thereof.
8 . The method of claim 7 , wherein the immunomer compound has the following structure (SEQ ID NO: 48):
9 . The method of claims 5 , 6 or 7 further comprising administering an antigen to the patient.
10 . The method of claim 9 wherein said antigen is an antigen associated with cancer, infectious disease or allergy.
11 . A composition comprising a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory oligonucleotide and a therapeutically effective synergistic amount of IL-2, wherein administration of said composition synergistically stimulates the production of one or more cytokines selected from the group consisting of IL-12 and IFN-γ, IFN-α, IFN-β or combinations thereof.
12 . A method for treating cancer in a patient comprising administering to a patient a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory oligonucleotide and a therapeutically effective synergistic amount of IL-2, wherein administration of said composition synergistically stimulates the production of one or more cytokines selected from the group consisting of IL-12 and IFN-γ, IFN-α, IFN-β or combinations thereof.
13 . The method of claim 12 , further comprising administering an antigen associated with cancer.
14 . A method for treating an allergy in a patient comprising administering to a patient a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory oligonucleotide and a therapeutically effective synergistic amount of IL-2, wherein administration of said composition synergistically stimulates the production of one or more cytokines selected from the group consisting of IL-12 and IFN-γ, IFN-α, IFN-β or combinations thereof.
15 . The method of claim 14 , further comprising administering an antigen associated with said allergy.
16 . A method for treating an infectious disease in a patient comprising administering to a patient a therapeutically effective synergistic amount of at least one immunomer compound or immunostimulatory oligonucleotide and a therapeutically effective synergistic amount of IL-2, wherein administration of said composition synergistically stimulates the production of one or more cytokines selected from the group consisting of IL-12 and IFN-γ, IFN-α, IFN-β or combinations therof.
17 . The method of claim 16 , further comprising administering an antigen associated with said infectious disease.
18 . A method of stimulating an immune response in a patient comprising administering to a patient a therapeutically effective synergistic amount of an immunostimulatory oligonucleotide comprising at least one immunostimulatory CpG dinucleotide, wherein C is not cytosine or deoxycytosine and/or G is not guanosine or 2-deoxyguanosine, and a therapeutically effective synergistic amount of IL-2.