Treatment of cancers with immunostimulatory HIV Tat derivative polypeptides
Disclosed herein are methods of treating cancer by administering a modified Human Immunodeficiency Virus (HIV) trans-activator of transcription (Tat) polypeptide with increased immunostimulatory properties relative to the non-modified Tat polypeptide.
1. A pharmaceutical composition comprising a modified amino acid sequence of Human Immunodeficiency Virus (HIV) trans-activator of transcription (Tat) protein wherein the modified amino acid sequence has greater than 95% sequence identity to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:3.
2. The pharmaceutical composition of claim 1 , wherein the modified amino acid sequence has greater than 95% sequence identity to the amino acid sequence of SEQ ID NO:2.
3. The pharmaceutical composition of claim 1 , wherein the modified amino acid sequence has greater than 95% sequence identity to the amino acid sequence of SEQ ID NO:3.
4. A method of treating breast or ovarian cancer comprising:
administering a therapeutically effective amount of a Tat derivative polypeptide comprising the modified amino acid sequence of claim 1 to a subject in need thereof; and causing cessation of growth of the cancer or regression of the cancer in the subject.
5. The method of claim 4 , wherein the Tat derivative polypeptide is administered in a plurality of doses.
6. The method of claim 4 , wherein the administering step comprises a repetitive administration cycle wherein each cycle comprises administering a plurality of doses of the Tat derivative polypeptide in a defined time period followed by a rest period and wherein the cycle is repeated a plurality of times.
7. The method of claim 4 , wherein the administering step comprises a repetitive administration cycle wherein each cycle comprises administering a plurality of doses of the Tat derivative polypeptide in a defined time period followed by a administration of one or a plurality of doses of a therapeutic agent in a defined time period and wherein the cycle is repeated a plurality of times.
8. The method of claim 7 , wherein the therapeutic agent is cyclophosphamide.
9. The method of claim 7 , wherein the cancer is breast cancer.
10. The method of claim 7 , wherein the cancer is ovarian cancer.
11. The method of claim 4 , wherein the Tat derivative polypeptide comprises a modified amino acid sequence having greater than 95% sequence identity to the amino acid sequence of SEQ ID NO:2.
12. The method of claim 4 , wherein the Tat derivative polypeptide comprises a modified amino acid sequence having greater than 95% sequence identity to the amino acid sequence of SEQ ID NO:3.
13. A method of reducing breast cancer tumor burden or ovarian cancer tumor burden comprising:
administering a therapeutically effective amount of the a Tat derivative polypeptide comprising the modified amino acid sequence of claim 1 to a subject in need thereof; and
causing regression of the cancer in the subject.
14. The method of claim 13 , wherein the Tat derivative polypeptide is administered in a plurality of doses.
15. The method of claim 13 , wherein the administering step comprises a repetitive administration cycle wherein each cycle comprises administering a plurality of doses of the Tat derivative polypeptide in a defined time period followed by a rest period and wherein the cycle is repeated a plurality of times.
16. The method of claim 13 , wherein the administering step comprises a repetitive administration cycle wherein each cycle comprises administering a plurality of doses of the Tat derivative polypeptide in a defined time period followed by an administration of one or a plurality of doses of a therapeutic agent in a defined time period and wherein the cycle is repeated a plurality of times.
17. The method of claim 16 , wherein the therapeutic agent is cyclophosphamide.
18. The method of claim 13 , wherein the cancer is breast cancer.
19. The method of claim 13 , wherein the cancer is ovarian cancer.