Claims
- 1. An isolated polypeptide comprising an immunogenic portion of a Wilms' tumor antigen, selected from the group consisting of SEQ ID NOs:478 and 502, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with WT1-specific antisera and/or T-cell lines or clones is not substantially diminished.
- 2. The isolated polypeptide according to claim 1 wherein the immunogenic portion has been modified such that the ability of the immunogenic portion to bind to an MHC molecule is increased relative to that of the immunogenic portion.
- 3. The isolated polypeptide according to claim 2 wherein the immunogenic portion has been modified such that the ability of the immunogenic portion to bind to HLA-A2 is increased relative to that of the unmodified immunogenic portion.
- 4. An isolated polypeptide comprising a Wilms' tumor antigen having a deletion of a proline rich region.
- 5. An isolated polypeptide according to claim 4 wherein said proline rich region is from about amino acid positions 54 to 68 of the Wilms' tumor antigen.
- 6. The isolated polypeptide of claim 5 wherein said polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NO:478 and 502.
- 7. A fusion protein comprising at least one polypeptide according to any one of claims 1, 2 or 4.
- 8. The fusion protein of claim 7 wherein said fusion partner is selected from the group consisting of Ra12, protein D, LYTA, a HIS tag, a targeting signal capable of directing a polypeptide to the endosomal/lysosomal compartment, twin arginine translocator, and truncated twin arginine translocator.
- 9. The fusion protein of claim 8 wherein the fusion protein comprises a twin arginine translocator signal peptide.
- 10. The fusion protein of claim 8 wherein the fusion partner comprises the amino acid sequence of any one of SEQ ID NOs:504 and 506.
- 11. The fusion protein of claim 10 wherein the fusion protein comprises the amino acid sequence of any one of SEQ ID NOs:470, 479-483, and 499.
- 12. An isolated polynucleotide encoding the fusion proteins of any one of claims 7, 9, and 11.
- 13. The isolated polynucleotide of claim 12 wherein the polynucleotide has been codon optimized for expression in E. coli.
- 14. The isolated polynucleotide of claim 12 wherein the polynucleotide comprises a sequence of any one of SEQ ID NOs: 469, 471, and 472-477 and 503, 505.
- 15. A composition comprising a polypeptide of claim 1, 4, 6, or 11 in combination with a pharmaceutically acceptable carrier or excipient.
- 16. A vaccine comprising a polypeptide of claim 1, 4, 6, or 11 in combination with a non-specific immune response enhancer.
- 17. The vaccine according to claim 15 wherein the non-specific immune response enhancer preferentially enhances a T cell response in a patient.
- 18. The vaccine according to claim 15, wherein the immune response enhancer is selected from the group consisting of 3d-MPL, MPL, RC-529, AGP's, Montamide ISA50, Seppic Montamide ISA 720, a cytokine, a microsphere, dimethyl dioctadecyl ammoniumbromide (DDA) based adjuvants, AS-1, AS-2, Ribi Adjuvant system based adjuvant, QS21, saponin based adjuvants, Syntex adjuvant in its microfluidized form, MV, ddMV, immune stimulating complex (iscom) based adjuvants, and inactivated toxins.
- 19. An expression vector comprising a polynucleotide of claim 12 operably linked to an expression control sequence.
- 20. A host cell transformed or transfected with an expression vector according to claim 19.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0001] This invention was made in part with government support under NIH SBIR Phase I grant number IR43 CA81752-01A1. The Government may have certain rights in this invention.
Continuation in Parts (6)
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Number |
Date |
Country |
Parent |
10286333 |
Oct 2002 |
US |
Child |
10427717 |
Apr 2003 |
US |
Parent |
10244830 |
Sep 2002 |
US |
Child |
10286333 |
Oct 2002 |
US |
Parent |
10195835 |
Jul 2002 |
US |
Child |
10244830 |
Sep 2002 |
US |
Parent |
10125635 |
Apr 2002 |
US |
Child |
10195835 |
Jul 2002 |
US |
Parent |
10002603 |
Oct 2001 |
US |
Child |
10125635 |
Apr 2002 |
US |
Parent |
09938864 |
Aug 2001 |
US |
Child |
10002603 |
Oct 2001 |
US |