WT1 HLA class II-binding peptides and compositions and methods comprising same
This invention provides WT1 peptides and methods of treating, reducing the incidence of, and inducing immune responses against a WT1-expressing cancer, comprising same.
1. An isolated WT1 peptide consisting of the amino acid sequence
RSDELVRHHNMHQRNMTKL
(SEQ ID No: 2)
or
PGCNKRYFKLSHLQMHSRKHTG.
(SEQ ID No: 4)
2. The isolated WT1 peptide of claim 1 , wherein said isolated WT1 peptide binds to an HLA class II molecule.
3. The isolated WT1 peptide of claim 2 , wherein said HLA class II molecule is an HLA-DRB molecule.
4. The isolated WT1 peptide of claim 3 , wherein said isolated WT1 peptide binds to a second HLA-DRB molecule, wherein said HLA-DRB molecule of claim 3 and said second HLA-DRB molecule are encoded by separate HLA-DRB alleles.
5. A composition comprising the isolated WT1 peptide of claim 2 and an additional isolated WT1 peptide selected from among SEQ ID NO:1-4, wherein said additional isolated WT1 peptide binds to an additional HLA class II molecule.
6. A composition comprising the isolated WT1 peptide of claim 4 and an additional isolated WT1 peptide selected from among SEQ ID NO:1-4, wherein said additional HLA class II molecule is a third HLA-DRB molecule that is different from said HLA-DRB molecule of claim 3 or said second HLA-DRB molecule of claim 4 .
7. The composition of claim 6 , wherein said additional isolated WT1 peptide binds to a fourth HLA-DRB molecule, wherein said third HLA-DRB molecule of claim 6 and said fourth HLA-DRB molecule are encoded by separate HLA-DRB alleles.
8. A composition comprising the isolated WT1 peptide of claim 1 and an HLA class I molecule-binding WT1 peptide selected from among SEQ ID NO:5-38.
9. The composition of claim 8 , wherein said HLA class I molecule is an HLA-A molecule.
10. The composition of claim 8 , wherein the amino acid sequence of said HLA class I molecule-binding WT1 peptide comprises a sequence selected from SEQ ID No: 5-38.
11. A composition comprising (a) the isolated WT1 peptide of claim 1 and (b) an adjuvant or a carrier.
12. The composition of claim 11 , wherein said adjuvant is QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, a growth factor, a cytokine, a chemokine, an interleukin, Montanide ISA 51, or GM-CSF.
13. The composition of claim 5 , wherein the isolated WT1 peptide has an amino acid sequence
PGCNKRYFKLSHLQMHSRKHTG
(SEQ ID No: 4)
and the additional isolated WT1 peptide is selected from SEQ ID No: 1-3.
14. A composition comprising (a) an antigen-presenting cell and (b) a peptide selected from
RSDELVRHHNMHQRNMTKL
(SEQ ID No: 2)
and
PGCNKRYFKLSHLQMHSRKHTG.
(SEQ ID No: 4)
15. The composition of claim 14 , further comprising an additional HLA class II molecule-binding peptide selected from among SEQ ID NO:1-4, or an HLA class I molecule-binding WT1 peptide selected from among SEQ ID NO:5-38.
16. The composition of claim 15 , wherein said HLA class I molecule is an HLA-A molecule.
17. The composition of claim 15 , wherein the amino acid sequence of said HLA class I molecule-binding WT1 peptide comprises a sequence selected from SEQ ID No: 5-38.
18. The composition of claim 14 , wherein said antigen-presenting cell presents said peptide on an HLA class II molecule thereof.
19. A composition comprising (a) the composition of claim 14 and (b) an adjuvant or a carrier.
20. The composition of claim 19 , wherein said adjuvant is QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, a growth factor, a cytokine, a chemokine, an interleukin, Montanide ISA 51, or GM-CSF.