Methods and compositions for cancer immunotherapy using flagellin-tumor associated antigen fusion protein expressing tumor cells
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 flagellin or fragment thereof and a tumor-associated antigen (TAA),
wherein the flagellin or fragment thereof is capable of binding to one or more of Toll-like receptor-5 (TLR5), Naip5 or Ipaf.
2. 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.
3. 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 flagellin or fragment thereof and a tumor associated antigen (TAA), in an effective amount for eliciting an anti-tumor immune response,
wherein the flagellin or fragment thereof is capable of binding to one or more of Toll-like receptor-5 (TLR5), Naip5 or Ipaf.
4. The method of claim 2 , wherein said DC has phagocytosed said tumor cell.
5. The method of claim 3 , wherein said patient is a human.
6. The method of claim 2 , wherein said tumor cell is an autologous cell.
7. The method of claim 2 , wherein said DC is an autologous cell.
8. The method of claim 2 , wherein said tumor cell is lethally irradiated.
9. The method of claim 2 , wherein said patient is a human.
10. The method of claim 3 , wherein said tumor cell is an autologous cell.
11. The method of claim 3 , wherein said tumor cell is lethally irradiated.
12. The method of claim 1 , wherein the flagellin comprises an amino acid sequence substantially identical to an amino acid sequence selected from the group consisting of SEQ NOs: 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20, or a fragment thereof.
13. The method of claim 1 , wherein the flagellin fragment comprises and an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 32.
14. The method of claim 3 , wherein the flagellin comprises an amino acid sequence substantially identical to an amino acid sequence selected from the group consisting of SEQ NOs: 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20, or a fragment thereof.
15. The method of claim 3 , wherein the flagellin fragment comprises and an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 32.