Immune stimulation by phosphorothioate oligonucleotide analogs

Abstract

Methods of stimulating a local immune response in selected cells or tissues employing immunopotentiating oligonucleotide analogs having at least one phosphorothioate internucleotide bond are provided. Methods of enhancing the efficacy of a therapeutic treatment by stimulating a local immune response in selected cells or tissues employing oligonucleotide analogs having at least one phosphorothioate bond are also provided. The oligonucleotide analogs may have antisense efficacy in addition to immunopotentiating activity. Methods of modulating cytokine release in skin cells and immunopotentiators which include oligonucleotide analogs having at least one phosphorothioate bond capable of eliciting a local inflammatory response are also provided.

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         26 . A method for stimulating an immune response in a human comprising: 
 administering by a route selected from the group consisting of inhalation, ophthalmic, intranasal, parenteral, oral and intradermal to the human as an immunopotentiator an amount of a phosphorothioate oligonucleotide analog effective to stimulate an immune response, wherein the phosphorothioate oligonucleotide analog is not antisense.    
     
     
         27 . The method of  claim 26 , wherein the phosphorothioate oligonucleotide analog is an immunopotentiator of an antibody response.  
     
     
         28 . The method of  claim 26 , wherein the human has cancer.  
     
     
         29 . The method of  claim 26 , wherein the human has an infection.  
     
     
         30 . The method of  claim 26 , wherein the human is having surgery.  
     
     
         31 . The method of  claim 26 , wherein the phosphorothioate oligonucleotide analog is formulated in a vehicle selected from the group consisting of liposomes and cationic lipids.  
     
     
         32 . The method of  claim 26 , wherein all of the internucleotide linkages of the phosphorothioate oligonucleotide analog are phosphorothioate linkages.  
     
     
         33 . The method of  claim 26 , wherein the phosphorothioate oligonucleotide analog includes at least one 2′-O-alkyl modification.  
     
     
         34 . The method of  claim 26 , wherein the 2′-O-alkyl modification is a 2′-O-methyl modification.  
     
     
         35 . The method of  claim 26 , wherein the 2′-O-alkyl modification is a 2′-O-propyl modification.  
     
     
         36 . The method of  claim 26 , further comprising administering a therapeutic modality, before, after or simultaneously with the phosphorothioate oligonucleotide analog.  
     
     
         37 . The method of  claim 26 , wherein the therapeutic modality is a drug.  
     
     
         38 . A method for stimulating a systemic or humoral immune response in a human comprising: 
 administering to the human as an immunopotentiator an amount of a phosphorothioate oligonucleotide analog formulated in a vehicle selected from the group consisting of liposomes and cationic lipids effective to stimulate the systemic or humoral immune response, wherein the phosphorothioate oligonucleotide analog is not antisense.    
     
     
         39 . The method of  claim 38 , wherein the phosphorothioate oligonucleotide analog is an immunopotentiator of an antibody response.  
     
     
         40 . The method of  claim 38 , wherein the human has cancer.  
     
     
         41 . The method of  claim 38 , wherein the human has an infection.  
     
     
         42 . The method of  claim 38 , wherein the human is having surgery.  
     
     
         43 . The method of  claim 38 , wherein all of the internucleotide linkages of the phosphorothioate oligonucleotide analog are phosphorothioate linkages.  
     
     
         44 . The method of  claim 38 , wherein the phosphorothioate oligonucleotide analog includes at least one 2′-O-alkyl modification.  
     
     
         45 . The method of  claim 38 , wherein the 2′-O-alkyl modification is a 2′-O-methyl modification.  
     
     
         46 . The method of  claim 38 , wherein the 2′-O-alkyl modification is a 2′-O-propyl modification.  
     
     
         47 . The method of  claim 38 , further comprising administering a therapeutic modality, before, after or simultaneously with the phosphorothioate oligonucleotide analog.  
     
     
         48 . The method of  claim 38 , wherein the therapeutic modality is a drug.