Methods and compositions for cancer immunotherapy using flagellin-tumor associated antigen fusion protein expressing tumor cells

Abstract

Provided are methods for inducing an anti-tumor immune response by immunizing a mammal with a composition comprising a tumor cell which expresses a NLR ligand and/or TLR ligand-TAA fusion protein or with an activated DC which has internalized a tumor cell which expresses an NLR- and/or TLR ligand-TAA fusion protein.

1 . A composition comprising a dendritic cell (DC), wherein said DC has internalized a tumor cell expressing a fusion protein, said fusion protein comprising:
 (a) a Toll-like receptor (TLR) ligand and a tumor-associated antigen (TAA), or   (b) a Nod-like receptor (NLR) ligand and a tumor-associated antigen (TAA), or   (c) a Toll-like receptor (TLR) ligand, a Nod-like receptor (NLR) ligand, and a tumor-associated antigen (TAA).   
     
     
         2 - 3 . (canceled) 
     
     
         4 . A method for inducing an anti-tumor immune response in a mammal in need thereof comprising administering to said mammal an immunogenically effective amount of the composition of  claim 1 . 
     
     
         5 . A method for treating a cancer in a patient in need of such treatment comprising administering to said patient the composition of  claim 1  in an effective amount for eliciting an anti-tumor immune response. 
     
     
         6 . A method for inducing an anti-tumor immune response in a mammal in need thereof comprising administering to said mammal an immunogenically effective amount of a composition comprising a tumor cell expressing a fusion protein, wherein said fusion protein comprises:
 (a) a TLR ligand and a tumor-associated antigen (TAA), or   (b) a Nod-like receptor (NLR) ligand and a tumor-associated antigen (TAA), or   (c) a Toll-like receptor (TLR) ligand, a Nod-like receptor (NLR) ligand, and a tumor-associated antigen (TAA).   
     
     
         7 . A method for treating a cancer in a patient in need of such treatment comprising administering to said patient a composition comprising a tumor cell expressing a fusion protein, wherein said fusion protein comprises:
 (a) a Toll-like receptor (TLR) ligand and a tumor associated antigen (TAA), in an effective amount for eliciting an anti-tumor immune response, or   (b) a Nod-like receptor (NLR) ligand and a tumor-associated antigen (TAA), or   (c) a Toll-like receptor (TLR) ligand, a Nod-like receptor (NLR) ligand, and a tumor-associated antigen (TAA).   
     
     
         8 - 11 . (canceled) 
     
     
         12 . The composition of  claim 1 , wherein said TLR ligand is a polypeptide. 
     
     
         13 . The composition of  claim 12 , wherein said TLR ligand is a flagellin or profilin-like protein (PLP), or a fragment thereof. 
     
     
         14 . The composition of  claim 1 , wherein said tumor cell has been transfected with a vector expressing said fusion protein. 
     
     
         15 . The composition of  claim 1 , wherein said DC is an autologous cell. 
     
     
         16 . The composition of  claim 1 , or wherein said tumor cell is lethally irradiated prior to internalization by said DC. 
     
     
         17 . The composition of  claim 1 , or wherein said DC has phagocytosed said tumor cell. 
     
     
         18 . The method of  claim 4 , wherein said DC has phagocytosed said tumor cell. 
     
     
         19 . The method of  claim 5 , wherein said DC has phagocytosed said tumor cell. 
     
     
         20 . The method of  claim 4 , wherein said anti-tumor immune response comprises a CD4 or CD8 T cell-mediated immune response. 
     
     
         21 . The method of  claim 6 , wherein said anti-tumor immune response comprises a CD4 or CD8 T cell-mediated immune response. 
     
     
         22 . The method of  claim 6 , wherein said mammal is a human. 
     
     
         23 . The method of  claim 7 , wherein said patient is a human. 
     
     
         24 . The composition of  claim 1 , wherein said NLR ligand is selected from the group consisting of a flagellin, an anthrax toxin, and a  Staphylococcus aureus  toxin, or a fragment thereof. 
     
     
         25 . The composition of  claim 1 , wherein said tumor cell is an autologous cell. 
     
     
         26 . The method of  claim 4 , wherein said tumor cell is an autologous cell. 
     
     
         27 . The method of  claim 5 , wherein said tumor cell is an autologous cell. 
     
     
         28 . The method of  claim 6 , wherein said tumor cell is an autologous cell. 
     
     
         29 . The method of  claim 4 , wherein said mammal is a human. 
     
     
         30 . The method of  claim 4 , wherein said DC is an autologous cell. 
     
     
         31 . The method of  claim 5 , wherein said DC is an autologous cell. 
     
     
         32 . The composition of  claim 1 (a), wherein said TLR ligand is also an NLR ligand. 
     
     
         33 . The composition of  claim 1 (b), wherein said NLR ligand is also a TLR ligand. 
     
     
         34 . The composition of  claim 1 (a), wherein said fusion protein further comprises a distinct NLR ligand. 
     
     
         35 . The composition of  claim 1 (b), wherein said fusion protein further comprises a distinct TLR ligand. 
     
     
         36 . The composition of  claim 32 , wherein said TLR ligand is profilin-like protein (PLP) and said NLR ligand is anthrax toxin, or a fragment thereof. 
     
     
         37 . The method of  claim 4 , wherein said tumor cell is lethally irradiated. 
     
     
         38 . The method of  claim 5 , wherein said tumor cell is lethally irradiated. 
     
     
         39 . The method of  claim 6 , wherein said tumor cell is lethally irradiated. 
     
     
         40 . The method of  claim 5 , wherein said patient is a human. 
     
     
         41 . The method of  claim 7 , wherein said tumor cell is an autologous cell. 
     
     
         42 . The composition of  claim 34 , wherein said TLR ligand is profilin-like protein (PLP) and said NLR ligand is anthrax toxin, or a fragment thereof. 
     
     
         43 . The method of  claim 7 , wherein said tumor cell is lethally irradiated.