Immunostimulatory combinations

Abstract

The present invention provides immunostimulatory combinations. Generally, the immunostimulatory combinations include a TLR agonist and a TNF/R agonist. Certain immunostimulatory combinations also may include an antigen.

1 . An immunostimulatory combination comprising: at least one TLR agonist and at least one TNF/R agonist, each in an amount that, in combination with the other(s), is(are) effective to synergistically increase a subject's immune response to a desired antigen, wherein the at least one TNF/R agonist comprises a 4-1BB agonist. 
     
     
         2 . The immunostimulatory combination of  claim 1  wherein the at least one TLR agonist is an agonist of at least one of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, or any combination of any of the foregoing. 
     
     
         3 . The immunostimulatory combination of  claim 2  wherein the TLR agonist comprises an IRM compound or an agonist of TLR2, or comprises MALP-2, LPS, polyIC, or CpG. 
     
     
         4 . (canceled) 
     
     
         5 . The immunostimulatory combination of  claim 3  wherein the IRM compound comprises an imidazoquinoline amine, a tetrahydroimidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, an imidazonaphthyridine amine, a tetrahydroimidazonaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine. 
     
     
         6 . (canceled) 
     
     
         7 . The immunostimulatory combination of  claim 1  wherein the at least one TNF/R agonist further comprises an agonist of CD40 ligand, OX40 ligand, CD27, CD30 ligand (CD153), TNFα, TNF-β, RANK ligand, LT-α, LT-β, GITR ligand, LIGHT and/or further comprises an agonist of CD40, OX40, 4-1BB, CD70 (CD27 ligand), CD30, TNFR2, RANK, LT-BR, HVEM, GIFR, TROY, or RELT. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The immunostimulatory combination of  claim 1  wherein the at least one TNF/R agonist comprises an agonistic antibody. 
     
     
         11 . A method of inducing a synergistic antigen-specific T H1  immune response and/or synergistically activating CD8 +  T cells specific to a desired antigen and/or elicit a synergistic cell-mediated immune response specific to a desired antigen in a subject with a disease condition associated with cells which express said desired antigen comprising: co-administering to the subject at least one TLR agonist and at least one TNF/R agonist, each in an amount that, when in combination with the other, is effective to induce a synergistic T H1  immune response and/or synergistically activating CD8 +  T cells specific to a desired antigen, wherein the at least one TNF/R agonist comprises a 4-1BB agonist. 
     
     
         12 - 15 . (canceled) 
     
     
         16 . The method of  claim 11  which further includes the administration of a desired antigen against which said synergistic T H1 immune response is elicited and/or to which antigen said activated CD8 +  T cells are specific. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The method of  claim 11  wherein activating CD8 +  T cells comprises expansion of CD8 +  effector T cells and/or generating antigen-specific CD8 +  memory T cells. 
     
     
         20 - 26 . (canceled) 
     
     
         27 . The method of  claim 11  wherein the at least one TNF/R agonist comprises an agonistic antibody. 
     
     
         28 . The method of activating or expanding antigen-specific memory CD8 +  T cells and/or generating antigen-specific CD8 +  memory T cells of  claim 19 , wherein the subject has had prior exposure to the desired antigen. 
     
     
         29 - 42 . (canceled) 
     
     
         43 . The method of  claim 11  wherein the condition comprises a neoplastic disease. 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The method of  claim 11  wherein the condition comprises an infectious disease. 
     
     
         47 - 48 . (canceled) 
     
     
         49 . The immunostimulatory combination of  claim 1 , which further comprises a desired antigen against which said synergistic immune response is elicited. 
     
     
         50 - 56 . (canceled) 
     
     
         57 . The immunostimulatory combination of  claim 49  wherein the antigen comprises a tumor antigen, a viral antigen, a bacterial antigen, or a parasitic antigen.