MODIFIED CpG OLIGODEOXYNUCLEOTIDE WITH IMPROVED IMMUNOREGULATORY FUNCTION

Abstract

The present invention relates to a modified CpG oligodeoxynucleotide (ODN) which is prepared by coupling a consecutive sequence of deoxyribothymine (dT) to the 3′-terminus of CpG ODN having immunoregularory function, thereby improving immunoactivity of splenocytes, macrophages and peripheral mononuclear cells, and therefore, can be effectively used as a vaccine adjuvant for preventing and treating hepatitis B or an anticancer agent. Since the phosphorothioate CpG ODN having the consecutive sequence of dT at its 3′-terminus shows high activity inducing Th-1 immune response and does not elicit in vivo toxicity with guaranteeing its safety, it can be effectively used as a vaccine adjuvant.

1 - 8 . (canceled) 
     
     
         9 . A method for treating cancer in a patient comprising:
 a) administering to a patient a structurally modified oligodeoxynucleotide (ODN) having immunoactivity and a CpG motif and consisting of the nucleotide sequence of SEQ ID NO: 5, wherein the ODN has a consecutive sequence of 4 deoxyribothymines (dT) at the 3′-terminus of ODN, which is modified by changing the phosphodiester bonds into phosphorothioated bonds;   b) allowing the composition to increase immunoactivity of splenocytes, macrophages or peripheral blood mononuclear cells thereby treating the cancer.   
     
     
         10 . A method for treating cancer in a patient comprising:
 a) administering to a patient a structurally modified oligodeoxynucleotide (ODN) having immunoactivity and a CpG motif and comprising the nucleotide sequence of SEQ ID NO: 5, wherein the ODN has a consecutive sequence of 4 deoxyribothymines (dT) at the 3′-terminus of ODN, which is modified by changing the phosphodiester bonds into phosphorothioated bonds;   b) allowing the composition to increase immunoactivity of splenocytes, macrophages or peripheral blood mononuclear cells thereby treating the cancer.   
     
     
         11 . A method for increasing immunoactivity of splenocytes, macrophages or peripheral blood mononuclear cells in a patient comprising:
 a) administering to a patient a structurally modified oligodeoxynucleotide (ODN) having immunoactivity and a CpG motif and consisting the nucleotide sequence of SEQ ID NO: 5, wherein the ODN has a consecutive sequence of 4 deoxyribothymines (dT) at the 3′-terminus of ODN, which is modified by changing the phosphodiester bonds into phosphorothioated bonds;   b) allowing the composition to increase immunoactivity of splenocytes, macrophages or peripheral blood mononuclear cells.   
     
     
         12 . A method for increasing immunoactivity of splenocytes, macrophages or peripheral blood mononuclear cells in a patient comprising:
 a) administering to a patient a structurally modified oligodeoxynucleotide (ODN) having immunoactivity and a CpG motif and comprising the nucleotide sequence of SEQ ID NO: 5, wherein the ODN has a consecutive sequence of 4 deoxyribothymines (dT) at the 3′-terminus of ODN, which is modified by changing the phosphodiester bonds into phosphorothioated bonds;   b) allowing the composition to increase immunoactivity of splenocytes, macrophages or peripheral blood mononuclear cells.   
     
     
         13 . The method of  claim 9 , wherein the ODN is administered in combination with a monoclonal antibody. 
     
     
         14 . The method of  claim 13 , wherein the monoclonal antibody is trastuzumab or rituximab. 
     
     
         15 . The method of  claim 9 , wherein the patient has melanoma, lymphoma, colon cancer, or breast cancer. 
     
     
         16 . The method of  claim 10 , wherein the ODN is administered in combination with a monoclonal antibody. 
     
     
         17 . The method of  claim 16 , wherein the monoclonal antibody is trastuzumab or rituximab. 
     
     
         18 . The method of  claim 10 , wherein the patient has melanoma, lymphoma, colon cancer, or breast cancer. 
     
     
         19 . The method of  claim 11 , wherein the ODN is administered in combination with a monoclonal antibody. 
     
     
         20 . The method of  claim 19 , wherein the monoclonal antibody is trastuzumab or rituximab. 
     
     
         21 . The method of  claim 11 , wherein the patient has melanoma, lymphoma, colon cancer, or breast cancer. 
     
     
         22 . The method of  claim 12 , wherein the ODN is administered in combination with a monoclonal antibody. 
     
     
         23 . The method of  claim 22 , wherein the monoclonal antibody is trastuzumab or rituximab. 
     
     
         24 . The method of  claim 12 , wherein the patient has melanoma, lymphoma, colon cancer, or breast cancer.