Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer
Disclosed herein are modified proaerolysin (PA) peptide. In some examples, the proteins include a prostate-specific protease cleavage site and can further include a prostate-tissue-specific binding domain which functionally replaces the native PA binding domain. In other examples, the proteins include a furin cleavage site and a prostate tissue-specific binding domain which functionally replaces the native PA binding domain. Methods of using such peptides to treat prostate cancer are also disclosed.
1. A purified peptide comprising the amino acid sequence shown in SEQ. ID NO:4.
2. The purified peptide of claim 1 , wherein the peptide further comprises a polyhistidine tag.
3. The purified peptide of claim 2 , wherein the polyhistidine tag comprises six histidines at the C-terminus of SEQ ID NO: 4.
4. A method for treating prostate cancer in a subject, comprising contacting prostate cancer cells of the subject with the peptide of claim 1 .
5. The method of claim 4 , wherein contacting prostate cancer cells of the subject with the peptide comprises administering the peptide to the subject.
6. The method of claim 5 , wherein the peptide is administered intratumorally and/or intraprostatically.
7. The method of claim 5 , wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally.
8. The method of claim 4 , wherein the subject has a localized prostate tumor.
9. The method of claim 4 , wherein the subject has a metastatic prostate tumor.
10. The method of claim 4 , further comprising administering granulocyte macrophage colony stimulating factor [GM-CSF] to the subject.
11. The method of claim 4 , further comprising administering irradiated prostate cancer cells to the subject.
12. The method of claim 4 , wherein administration results in a reduction in prostate tumor cell volume.
13. The method of claim 4 , wherein administration results in a reduction of a metastatic prostate tumor.
14. The method of claim 9 , wherein administration results in treatment of the metastatic prostate tumor.
15. A method for treating prostate cancer in a subject, comprising contacting prostate cancer cells of the subject with a peptide consisting of the amino acid sequence shown in SEQ ID NO:4.
16. A method for treating prostate cancer in a subject, comprising administering a peptide consisting of the amino acid sequence shown in SEQ ID NO:4 to the subject.
17. The method of claim 16 , wherein the peptide is administered intratumorally and/or intraprostatically.
18. The method of claim 16 , wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally.
19. The method of claim 15 , wherein the subject has a localized prostate tumor.
20. The method of claim 15 , wherein the subject has a metastatic prostate tumor.
21. A method for treating prostate cancer in a subject, comprising administering the peptide of claim 2 , to the subject.
22. The method of claim 21 , wherein the peptide is administered intratumorally and/or intraprostatically.
23. The method of claim 21 , wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally.
24. The method of claim 21 , wherein the subject has a localized prostate tumor.
25. The method of claim 21 , wherein the subject has a metastatic prostate tumor.
26. A method for treating prostate cancer in a subject, comprising administering the peptide of claim 3 to the subject.
27. The method of claim 26 wherein the peptide is administered intratumorally and/or intraprostatically.
28. The method of claim 26 , wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally.
29. The method of claim 26 , wherein the subject has a localized prostate tumor.
30. The method of claim 26 , wherein the subject has a metastatic prostate tumor.