Synthetic HLA binding WT-1 peptide analogues and uses thereof
The present invention is directed to a synthetic peptide comprising a sequence of amino acids containing at least a segment that is an analogue of a native peptide that specifically binds to HLA A0201 or HLA A0301 molecules on a cell characteristic of a pathophysiologic state in a mammal. The synthetic peptide may be derived from native peptides comprising a breakpoint region of the WT1 protein.
1. A synthetic WT-1 peptide, comprising a sequence of amino acids that is an analogue peptide of a native WT-1 peptide, wherein said analogue specifically binds to HLA A0201 or HLA A0301 molecules on a human cell, wherein the analogue peptide sequence is GLRRGIQDV (SEQ ID NO: 28).
2. The synthetic WT-1 peptide of claim 1 , wherein said analogue peptide is a degradation product of said synthetic WT-1 peptide.
3. The synthetic WT-1 peptide of claim 1 , further comprising: an immunogenic carrier linked thereto.
4. The synthetic WT-1 peptide of claim 3 , wherein said immunogenic carrier is a cater protein, a carrier peptide or an antigen-presenting cell.
5. The synthetic WT-1 peptide of claim 4 , wherein said carrier protein or carrier peptide is keyhole limpet hemocyanin, an albumin or a polyamino acid.
6. The synthetic WT-1 peptide of claim 4 , wherein said antigen presenting cell is a dendritic cell.
7. The synthetic WT-1 peptide of claim 1 , wherein said native WT-1 peptide is GVFRGIQDV (SEQ ID NO: 27).
8. A synthetic WT-1 peptide consisting of the amino acid sequence GLRRGIQDV (SEQ ID NO: 28).
9. The synthetic WT-1 peptide of claim 1 , wherein said analogue peptide differs from said native WT-1 peptide in a major histocompatibility complex (MHC) molecule anchor residue.
10. The synthetic WT-1 peptide of claim 1 , wherein said human cell is characteristic of a pathophysiologic state.
11. The synthetic WT-1 peptide of claim 10 , wherein said pathophysiologic state is a cancer selected from the group consisting of a leukemia, a breast cancer, a lymphoma, a mesothelioma, a lung cancer, a testicular cancer, and an ovarian cancer.
12. The synthetic WT-1 peptide of claim 11 , wherein said leukemia is a chronic myelogenous leukemia.
13. A pharmaceutical composition, comprising: a therapeutically effective amount of the synthetic WT-1 peptide of claim 1 ; and a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , further comprising an adjuvant, a diluent or a combination thereof.
15. The pharmaceutical composition of claim 14 , wherein said adjuvant is a protein, a peptide or an antigen presenting cell linked to said synthetic peptide.
16. The pharmaceutical composition of claim 15 , wherein said protein or peptide is keyhole limpet hemocyanin, an albumin or a polyamino acid.
17. The pharmaceutical composition of claim 15 , wherein said antigen presenting cell is a dendritic cell.