Guanosine as an Immune Potentiator Mediated through Toll Receptors

Abstract

Methods and Compositions involving the administration of guanosine, identified as Toll like receptor (TLR) 2 and 4 agonists, that will be useful for enhancing the potency of vaccine and cancer immunotherapies are disclosed. Method of preventing and treating cancer and infection by administration of guanosine or pro-drugs of guanosine, or a precursor of guanosine are also disclosed. Compositions of guanosine or a pro-drug of guanosine or precursor of guanosine may be formulated as pharmaceutical dosage forms and components can be assembled as kits. Methods for activating TLRs with guanosine to enhance an immune response and to potentiate/augment antiviral, antibacterial or anticancer effects of other antiviral, anti-bacterial and anticancer therapeutic agents are also disclosed.

1 - 8 . (canceled) 
     
     
         9 . A method for treating infectious disease in a subject, the method comprising administering a pharmaceutically effective amount of one or more of: guanosine, a pro-drug thereof, and a precursor thereof. 
     
     
         10 . The method according to  claim 9  wherein the guanosine precursor is guanosine mono phosphate (GMP) or a salt or pro-drug thereof. 
     
     
         11 . A method for treating cancer in a subject, the method comprising administering a pharmaceutically effective amount of guanosine or a pro-drug thereof or a precursor of guanosine. 
     
     
         12 . The method according to  claim 11  wherein the guanosine precursor is guanosine mono phosphate (GMP) or a salt thereof, or a prodrug thereof. 
     
     
         13 . A method for enhancing a potentiating treatment with an anti-cancer, anti-viral or anti-bacterial agent, the method comprising administering guanosine or a pro drug thereof or a precursor of guanosine to the subject in conjunction with the anti-cancer, anti-viral, or anti-bacterial agent. 
     
     
         14 . The method according to  claim 13  wherein an anti-viral agent is selected from the group consisting of simeprevir, sofosbuvir, ledipasavir, ABT-267, ABT-333, tenofovir, entecavir, and atripla. 
     
     
         15 . The method according to  claim 13  wherein the guanosine precursor is guanosine mono phosphate (GMP) or a salt thereof, or a prodrug thereof. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . A method for activating toll like receptor (TLR) 2 and TLR 4 in a subject, the method comprises administering a pharmaceutically effective amount of guanosine or a pro-drug of guanosine, or a precursor of guanosine to the subject in conjunction with the vaccine or immunotherapy. 
     
     
         19 . The method according to  claim 18  wherein the guanosine precursor is guanosine mono phosphate (GMP) or a salt thereof, or a prodrug thereof. 
     
     
         20 . The method according to  claim 13  wherein the anti-viral agent is selected from the group consisting of compounds targeting viral polymerases, compounds targeting viral proteases, and compounds targeting other structural and non-structural viral proteins.