Targeted innate immunity

Abstract

Provided is a cancer therapeutic agent comprising a cancer targeting molecule linked to a CpG oligodeoxynucleotide. Also provided are methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer, comprising administering an effective amount of the cancer therapeutic agent. The methods may also include reducing immunoregulatory T cell activity in the individual.

1 . A cancer therapeutic agent comprising a cancer targeting molecule linked to an oligonucleotide comprising an immunostimulatory sequence motif which contains at least one unmethylated CG dinucleotide.  
     
     
         2 . The cancer therapeutic agent of  claim 1  wherein said cancer targeting molecule is an antibody.  
     
     
         3 . The cancer therapeutic agent of  claim 2  wherein said antibody is specific for a tumor cell-surface antigen.  
     
     
         4 . The cancer therapeutic agent of  claim 2 , wherein said antibody is specific for a stromal component of a tumor.  
     
     
         5 . The cancer therapeutic agent of  claim 2 , wherein said antibody is specific for an intracellular antigen.  
     
     
         6 . The cancer therapeutic agent of  claim 5 , wherein said antibody is specific for an intranuclear antigen.  
     
     
         7 . The cancer therapeutic agent of  claim 2 , wherein said antibody is human or humanized.  
     
     
         8 . The cancer therapeutic agent of  claim 1 , wherein said oligonucleotide contains multiple immunostimulatory sequence motifs.  
     
     
         9 . The cancer therapeutic agent of  claim 8 , wherein said immunostimulatory sequence motif of said oligonucleotide is TCGTT or TCGTA or both.  
     
     
         10 . The cancer therapeutic agent of  claim 1 , wherein said cancer targeting molecule is linked to multiple oligonucleotides that comprise an immunostimulatory sequence motif which contains at least one unmethylated CG dinucleotide.  
     
     
         11 . The cancer therapeutic agent of  claim 1  wherein said immunostimulatory sequence motif of said oligonucleotide binds to human Toll-Like Receptor 9.  
     
     
         12 . A cancer therapeutic agent of  claim 1  further comprising a pharmaceutically acceptable carrier.  
     
     
         13 . A method of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or reducing or inhibiting the development of metastatic cancer in an individual suffering from cancer, comprising administering an effective amount of a cancer therapeutic agent to the individual wherein said cancer therapeutic agent comprises a cancer targeting molecule linked to a CpG oliognucleotide.  
     
     
         14 . The method of  claim 13 , further comprising the step of reducing immunoregulatory T cell activity in the individual.  
     
     
         15 . The method of  claim 14 , wherein reducing immunoregulatory T cell activity is achieved by removing ex vivo immunoregulatory T cells from the individual.  
     
     
         16 . The method of  claim 14 , wherein reducing immunoregulatory T cell activity is achieved by administering an agent to the individual that depletes or inactivates immunoregulatory T cells in the individual.  
     
     
         17 . The method of  claim 14 , wherein reducing immunoregulatory T cell activity is achieved using at least one antibody that binds to the immunoregulatory T cells.  
     
     
         18 . The method of  claim 17 , wherein said antibody is selected from the group consisting of anti-CD4, anti-CD25, anti-neuropilin, and anti-CTLA4.  
     
     
         19 . The method of  claim 14 , wherein reducing immunoregulatory T cell activity is achieved by administering a GITR ligand agonist.  
     
     
         20 . The method of  claim 14 , wherein reducing immunoregulatory T cell activity is performed before administering said cancer therapeutic agent.  
     
     
         21 . The method of  claim 14 , further comprising administering T cells which have cytotoxic activity against the cancer.  
     
     
         22 . The method of  claim 21 , wherein said administering T cells comprises removing T cells from the individual, activating the T cells, and then administering the activated T cells to the individual.