Modulation of immunostimulatory properties by small oligonucleotide-based compounds

Abstract

The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers of the invention comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5′ end.

1 . A method for therapeutically treating a patient having airway inflammation, inflammatory disorders, allergy, or asthma, such method comprising administering to the patient an immunomer, wherein the immunomer has the sequence of 5′-TCRTCRTTG-X-GTTRCTRCT-5′, wherein R is arabinoguanosine and X is glycerol linker. 
     
     
         2 . The method according to  claim 1 , further comprising administering an antigen associated with said disease or disorder. 
     
     
         3 . The method according to  claim 1 , wherein the immunomer or the antigen, or both, are linked to an immunogenic protein or non-immunogenic protein. 
     
     
         4 . The method according to  claim 1 , further comprising administering an adjuvant. 
     
     
         5 . The method according to  claim 1 , further comprising administering a co-stimulatory molecule selected from the group consisting of cytokines, chemokines, protein ligands, a trans-activating factors, peptides, and peptides comprising a modified amino acid. 
     
     
         6 . A method for preventing airway inflammation, inflammatory disorders, allergy, or asthma in a patient, such method comprising administering to the patient an immunomer, wherein the immunomer has the sequence of 5′-TCRTCRTTG-X-GTTRCTRCT-5′, wherein R is arabinoguanosine and X is glycerol linker. 
     
     
         7 . The method according to  claim 6 , further comprising administering an antigen associated with said disease or disorder. 
     
     
         8 . The method according to  claim 6 , wherein the immunomer or the antigen, or both, are linked to an immunogenic protein or non-immunogenic protein. 
     
     
         9 . The method according to  claim 6 , further comprising administering an adjuvant. 
     
     
         10 . The method according to  claim 6 , further comprising administering a co-stimulatory molecule selected from the group consisting of cytokines, chemokines, protein ligands, a trans-activating factors, peptides, and peptides comprising a modified amino acid.