Treatment of cancer with alpha thymosin peptide and PD-1 inhibitors
The present invention provides compositions and methods for treating cancer or a metastasis thereof in a subject. In some embodiments, the methods involve administering a composition comprising therapeutically effective amount of at least one immune stimulator to the subject. In some embodiments, a combination of at least two immune stimulators is used for the treatment. In some embodiments, the combination includes an alpha thymosin peptide and an additional immune stimulator, and/or optionally one or more additional anti-cancer agents.
1. A method of treating cancer or a metastasis thereof in a subject comprising administering a therapeutically effective amount of an alpha thymosin peptide and a therapeutically effective amount of a programmed cell death-1 (PD-1) inhibitor.
2. The method of claim 1 , wherein the subject is a human.
3. The method of claim 1 , wherein the PD-1 inhibitor is administered to the subject at a dosage of about 0.01-1000 mg/day.
4. The method of claim 1 , wherein the alpha thymosin peptide is administered to the subject during at least a portion of the treatment at a dosage within a range of about 0.1-10 mg/day.
5. The method of claim 4 , wherein the dosage of the alpha thymosin peptide is within a range of about 0.5-10 mg/day.
6. The method of claim 1 , wherein the alpha thymosin peptide is thymosin alpha 1 (TA1).
7. The method of claim 6 , comprising administration of TA1 daily for a period of about 1-10 days, followed by about 1-5 days of non-administration of TA1.
8. The method of claim 7 , wherein TA1 is administered daily for about 3-5 days, followed by about 2-4 days of non-administration of TA1.
9. The method of claim 8 , wherein TA1 is administered daily for about 4 days, followed by about 3 days non-administration of TA1.
10. The method of claim 1 , wherein the method further comprises administering a kinase inhibitor.
11. The method of claim 10 , wherein the kinase inhibitor comprises sorafenib.
12. The method of claim 10 , wherein the kinase inhibitor is administered to the subject at a dosage within a range of about 10-200 mg/kg/day.
13. The method of claim 1 , wherein the method further comprises administering an antineoplastic heat shock apoptosis activator (HSAA).
14. The method of claim 13 , wherein the HSAA comprises STA-4783 (elesclomol).
15. The method of claim 13 , wherein the HSAA is administered to the subject at a dosage within a range of about 0.01-100 mg/kg/day.
16. The method of claim 1 , wherein the method further comprises administering a cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibody.
17. The method of claim 16 , wherein the CTLA4 antibody comprises 9H10, MDC010, 1F4, BNI3, Q01, A01, M08, 1B8, WKH203, ab9984, ab13486, ipilimumab, ticilimumab or a combination thereof.
18. The method of claim 16 , wherein the CTLA4 antibody is administered to the subject at a dosage within a range of about 0.001-50 mg/kg/day.
19. The method of claim 1 , wherein the method further comprises administering an alkylating antineoplastic agent (AlkAA).
20. The method of claim 19 , wherein the alkylating antineoplastic agent (AlkAA) comprises dacarbazine (DTIC).
21. The method of claim 19 , wherein the alkylating antineoplastic agent (AlkAA) is administered to the subject at a dosage within a range of about 700-1300 mg/kg/day.
22. The method of claim 1 , wherein the method further comprises administering a chemotherapeutic agent to the subject.
23. The method of claim 22 , wherein the chemotherapeutic agent is dacarbazine (DTIC) or cisplatin.
24. The method of claim 1 , wherein the cancer is melanoma.
25. The method of claim 24 , wherein the method further comprises administering an additional anti-melanoma agent.
26. The method of claim 1 , wherein the method further comprises administering an anti-cancer agent.
27. The method of claim 1 , wherein the PD-1 inhibitor is an antibody against PD-1.
28. The method of claim 1 , wherein the PD-1 inhibitor is an agent that inhibits the ligand for PD-1.
29. The method of claim 28 , wherein the agent that inhibits the ligand for PD-1 is an anti-PD-L1 antibody.
30. The method of claim 1 , wherein the PD-1 inhibitor is administered to the subject at a dosage of about 0.1 to 10 mg/kg.
31. The method of claim 1 , wherein the alpha thymosin peptide is administered to the subject during at least a portion of the treatment at a dosage of about 0.01 to about 6 mg/kg.