Claims
- 1. A purified peptide comprising a variant proaerolysin amino acid sequence, wherein the variant proaerolysin amino acid sequence comprising a prostate-specific protease cleavage site and a functionally deleted furin cleavage site.
- 2. The peptide of claim 1, wherein the prostate-specific cleavage site comprising prostate-specific antigen (PSA) cleavage site, a prostate membrane antigen (PSMA) cleavage site, or a human glandular kallikrein 2 (hK2) cleavage site.
- 3. The peptide of claim 2, wherein the PSA cleavage site comprising SEQ ID NO: 5, 8, 11, 14, 15, 16, 17, 18, 19, 20, or 21.
- 4. The peptide of claim 2, wherein the PSA cleavage site comprising SEQ ID NO: 5.
- 5. The peptide of claim 1, wherein the variant proaerolysin amino acid sequence further comprising a functionally deleted binding domain.
- 6. The peptide of claim 5, wherein the binding domain is functionally deleted by deletion of amino acids 1-83 of SEQ ID NO: 2 or 4.
- 7. The peptide of claim 4, wherein the binding domain is functionally deleted by deletion of at least one mutation selected from the group consisting of W45A, I47E, M57A, Y61A, and K66Q of SEQ ID NO: 2 or 4.
- 8. The peptide of claim 5, wherein the prostate-tissue specific binding domain.
- 9. The peptide of claim 8, wherein the prostate-tissue specific binding domain comprising a luteinizing hormone releasing hormone (LHRH) sequence.
- 10. The peptide of claim 9, wherein the LHRH sequence comprises SEQ ID NO: 22 or 23.
- 11. The peptide of claim 6, wherein the peptide further comprises an LHRH sequence linked to an N-terminus of the variant proaerolysin.
- 12. The peptide of claim 7, wherein the LHRH sequence is linked to amino acid 215 or 300 of SEQ ID NO: 2 or 4, wherein amino acid 215 or 300 has been mutated to a cysteine.
- 13. The peptide of claim 8, wherein the prostate-tissue specific binding domain comprises an antibody that recognizes PSA, hK2, PSMA or LHRH.
- 14. The peptide of claim 13, wherein the antibody is linked to an N-terminus of the variant proaerolysin.
- 15. The peptide of claim 13, wherein the antibody is linked to an C-terminus of the variant proaerolysin.
- 16. The peptide of claim 9, wherein the peptide sequence comprises SEQ ID NO: 24 or 25.
- 17. The peptide of claim 1, wherein the peptide is immobilized to a surface.
- 18. The peptide of claim 17, wherein the surface is a bead.
- 19. The peptide of claim 18, wherein the bead further comprises a prostate-specific ligand.
- 20. A method for treating prostate cancer in a subject, comprising administration of the peptide of claim 1 to the subject.
- 21. The method of claim 20, wherein the peptide is administered intratumorally and/or intraprostatically.
- 22. The method of claim 20, wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally.
- 23. A method for treating prostate cancer in a subject, comprising administration of a nucleic acid sequence that encodes the peptide of claim 1 to the subject.
- 24. A method for treating prostate cancer in a subject, comprising contacting prostate cancer cells of the subject with the peptide of claim 1.
- 25. The method of claim 20, wherein the subject has a localized prostate tumor.
- 26. A method for systemically treating prostate cancer in a subject, comprising:
removing prostate cancer cells from the subject; contacting the cells with the peptide of claim 1, thereby generating a cell lysate; and administering the cell lysate to the subject.
- 27. The method of claim 26, wherein the subject has a metastatic prostate tumor.
- 28. The method of claim 26, further comprising administering GM-CSF to the subject.
- 29. The method of claim 28, further comprising administering irradiated prostate cancer cells to the subject.
- 30. The method of claim 20, wherein administration results in a reduction in prostate tumor cell volume.
- 31. The method of claim 30, wherein the prostate tumor cell volume is reduced by at least 10%.
- 32. The method of claim 26, wherein administration results in a reduction prostate tumor cell volume.
- 33. The method of claim 32, wherein administration further results in a reduction of a metastatic prostate tumor.
- 34. The method of claim 32, wherein administration further results in treatment of a metastatic prostate tumor.
- 35. A purified peptide comprising a variant proaerolysin amino acid sequence, wherein the variant proaerolysin amino acid sequence comprises a furin cleavage site, a functionally deleted proaerolysin binding domain, and a prostate-tissue specific binding domain.
- 36. The peptide of claim 35, wherein the prostate-tissue specific binding domain comprises a PSA antibody, an hK2 antibody, a PSMA antibody, a LHRH antibody, an LHRH sequence, a peptide sequence that binds PSMA, or any peptide sequence that selectively binds to prostate cancer cells.
- 37. A purified peptide comprising a variant Clostridium septicum alpha toxin amino acid sequence, wherein the variant Clostridium septicum alpha toxin amino acid sequence comprises a prostate-specific protease cleavage site and a functionally deleted furin cleavage site.
- 38. A purified peptide comprising a variant Bacillus thuringiensis delta-toxin amino acid sequence, wherein the variant Bacillus thuringiensis delta-toxin amino acid sequence comprises a prostate-specific protease cleavage site and a functionally deleted wild type activation sequence.
- 39. A purified peptide comprising a variant human perforin amino acid sequence, wherein the variant human perforin amino acid sequence comprises a prostate-specific protease cleavage site and a functionally deleted wild type perforin activation site.
- 40. A purified peptide comprising a variant Clostridium septicum alpha toxin amino acid sequence, wherein the variant Clostridium septicum alpha toxin amino acid sequence comprises a furin cleavage site, a functionally deleted Clostridium septicum alpha toxin binding domain, and a prostate-tissue specific binding domain.
- 41. A purified peptide comprising a variant Bacillus thuringiensis delta-toxin amino acid sequence, wherein the variant Bacillus thuringiensis delta-toxin amino acid sequence comprises a wild type activation site, a functionally deleted Bacillus thuringiensis delta-toxin binding domain, and a prostate-tissue specific binding domain.
- 42. A purified peptide comprising a variant human perforin amino acid sequence, wherein the variant human perforin amino acid sequence comprises a wild type activation site, a functionally deleted perforin binding domain, and a prostate-tissue specific binding domain.
- 43. A purified nucleic acid sequence encoding the peptide of claim 1.
- 44. The method of claim 30, wherein the prostate tumor cell volume is reduced by at least 50%.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of priority to U.S. Provisional Application No. 60/314,613, filed Aug. 24, 2001, herein incorporated by reference in its entirety.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US02/27061 |
8/23/2002 |
WO |
|
Provisional Applications (1)
|
Number |
Date |
Country |
|
60314613 |
Aug 2001 |
US |