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, pro-cytolytic, peptide comprising at least 95% sequence identity to the amino acid sequence shown in SEQ ID NO:4, wherein the amino acid sequence at the positions corresponding to positions 427-432 of SEQ ID NO:4 is the sequence set forth in SEQ ID NO:5.
2. The purified peptide of claim 1 wherein the peptide comprises wherein the peptide comprises at least 98% sequence identity to the amino acid sequence shown in SEQ ID NO:4.
3. The purified peptide of claim 1 wherein the peptide comprises wherein the peptide comprises at least 98% sequence identity to the amino acid sequence shown in SEQ ID NO:4.
4. The purified peptide of claim 1 , wherein the peptide further comprises a polyhistidine tag.
5. The purified peptide of claim 4 , wherein the polyhistidine tag comprises six histidines at the C-terminus of SEQ ID NO: 4.
6. A purified nucleic acid molecule encoding the peptide of claim 1 .
7. A method for treating prostate cancer in a subject, comprising contacting prostate cancer cells of the subject with the peptide of claim 1 .
8. The method of claim 7 , wherein contacting prostate cancer cells of the subject with the peptide comprises administering the peptide to the subject.
9. The method of claim 8 , wherein the peptide is administered intratumorally and/or intraprostatically.
10. The method of claim 8 , wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally.
11. The method of claim 7 , wherein the subject has a localized prostate tumor.
12. The method of claim 7 , wherein the subject has a metastatic prostate tumor.
13. The method of claim 7 , further comprising administering granulocyte macrophage colony stimulating factor [GM-CSF] to the subject.
14. The method of claim 7 , wherein administration results in a reduction in prostate tumor cell volume.
15. The method of claim 7 , wherein administration results in a reduction of a metastatic prostate tumor.
16. The method of claim 12 , wherein administration results in treatment of the metastatic prostate tumor.
17. A method for treating prostate cancer in a subject, comprising administering the peptide of claim 4 to the subject.
18. The method of claim 17 wherein the peptide is administered intratumorally and/or intraprostatically.
19. The method of claim 18 , wherein the subject has a localized prostate tumor.