Method of treating cancer
The invention provides a method for treating cancer using a coadministration strategy that combines local codelivery of a therapeutic agent and an intracellular penetration enhancing agent, and optionally in further combination with local administration of an immunotherapeutic agent, such as a cancer vaccine or NKT agonist. The invention also provides a method for treating cancer using an intracellular penetration enhancing agent. The methods of the invention aim to substantially kill and/or destroy the target tumor cells, as well as those cancerous cells that have metastasized to other parts of the body.
1. A method of treating cancer in a subject in need thereof comprising intratumorally administering a pharmaceutical composition comprising an aqueous solution, the aqueous solution comprising a therapeutically effective amount of a therapeutic agent and an intracellular permeation enhancing agent, wherein the therapeutic agent is a chemotherapeutic agent, an interfering RNA, a therapeutic protein or a therapeutic antibody, wherein the therapeutic agent is mixed with and not covalently bound to the intracellular permeation enhancing agent, and wherein the intracellular permeation enhancing agent is 6-Oxo-6-phenylhexanoic acid, 8-Oxo-8-phenyloctanoic acid, 8-(2,5-Dichlorophenyl)-8-oxooctanoic acid, N-[8-(2-hydroxybenzoyl)aminooctanoic acid, N-[8-(2-hydroxybenzoyl)aminodecanoic acid, N-(5-chlorosalicyloyl)-8-aminocaprylic acid, N-[4-(4-chloro-2hydroxybenzoyl)amino1 butanoic acid, 2-ethylhexyl 2-hydroxybenzoate, 5-Cyclohexyl-5-oxovaleric acid, 6-Cyclohexyl-6-oxohexanoic acid, 7-Cyclohexyl-7-oxoheptanoic acid, 8-Cyclohexyl-8-oxooctanoic acid, 4-Cyclopentyl-4-oxobutyric acid, 5-Cyclopentyl-5-oxovaleric acid, 6-Cyclopentyl-6-oxohexanoic acid, 7-Cyclopentyl-7-oxoheptanoic acid, 8-Cyclopentyl-8-oxooctanoic acid, 4-Cyclobutyl-4-oxobutyric acid, 5-Cyclobutyl-5-oxovaleric acid, 6-Cyclobutyl-6-oxohexanoic acid, 7-Cyclobutyl-7-oxoheptanoic acid, 8-Cyclobutyl-8-oxooctanoic acid, 4-Cyclopropyl-4-oxobutyric acid, 5-Cyclopropyl-5-oxovaleric acid, 6-Cyclopropyl-6-oxohexanoic acid, 7-Cyclopropyl-7-oxoheptanoic acid, 8-Cyclopropyl-8-oxooctanoic acid, a functionally effective salt of any of the foregoing, or any combination thereof.
2. The method of claim 1 , wherein the intracellular permeation enhancing agent is N-[8-(2-hydroxybenzoyl)aminooctanoic acid.
3. The method of claim 1 , wherein the intracellular permeation enhancing agent is 6-Oxo-6-phenylhexanoic acid.
4. The method of claim 1 , wherein the intracellular permeation enhancing agent is 8-Cyclohexyl-8-oxooctanoic acid.
5. The method of claim 1 , wherein the intracellular permeation enhancing agent is 8-(2,5-Dichlorophenyl)-8-oxooctanoic acid.
6. The method of claim 1 , wherein the intracellular permeation enhancing agent is 7-Cyclohexyl-7-oxoheptanoic acid.
7. The method of claim 1 , wherein the therapeutic agent is a platinum agent.
8. The method of claim 1 , wherein the therapeutic agent is cisplatin.
9. The method of claim 1 , wherein the therapeutic agent is a vinca alkaloid agent.
10. The method of claim 1 , wherein the therapeutic agent is vinblastine.
11. The method of claim 1 , wherein the therapeutic agent is cisplatin and vinblastine.
12. A method of treating cancer in a subject in need thereof comprising intratumorally administering a pharmaceutical composition comprising an aqueous solution, the aqueous solution comprising a therapeutically effective amount of a therapeutic agent and an intracellular permeation enhancing agent, wherein the therapeutic agent is a chemotherapeutic agent, an interfering RNA, a therapeutic protein or a therapeutic antibody, and wherein the therapeutic agent is mixed with and not covalently bound to the intracellular permeation enhancing agent, wherein the intracellular permeation enhancing agent is 6-Oxo-6-phenylhexanoic acid, 8-Oxo-8-phenyloctanoic acid, 8-(2,5-Dichlorophenyl)-8-oxooctanoic acid, N-[8-(2-hydroxybenzoyl)aminooctanoic acid, N-[8-(2-hydroxybenzoyl)aminodecanoic acid, N-(5-chlorosalicyloyl)-8-aminocaprylic acid, N-[4-(4-chloro-2hydroxybenzoyl)amino1 butanoic acid, 2-ethylhexyl 2-hydroxybenzoate, 5-Cyclohexyl-5-oxovaleric acid, 6-Cyclohexyl-6-oxohexanoic acid, 7-Cyclohexyl-7-oxoheptanoic acid, 8-Cyclohexyl-8-oxooctanoic acid, 4-Cyclopentyl-4-oxobutyric acid, 5-Cyclopentyl-5-oxovaleric acid, 6-Cyclopentyl-6-oxohexanoic acid, 7-Cyclopentyl-7-oxoheptanoic acid, 8-Cyclopentyl-8-oxooctanoic acid, 4-Cyclobutyl-4-oxobutyric acid, 5-Cyclobutyl-5-oxovaleric acid, 6-Cyclobutyl-6-oxohexanoic acid, 7-Cyclobutyl-7-oxoheptanoic acid, 8-Cyclobutyl-8-oxooctanoic acid, 4-Cyclopropyl-4-oxobutyric acid, 5-Cyclopropyl-5-oxovaleric acid, 6-Cyclopropyl-6-oxohexanoic acid, 7-Cyclopropyl-7-oxoheptanoic acid, 8-Cyclopropyl-8-oxooctanoic acid, a functionally effective salt of any of the foregoing, or any combination thereof, and further comprising administering a therapeutically effective amount of an immunotherapeutic agent.
13. The method of claim 12 , wherein the intracellular permeation enhancing agent is N-[8-(2-hydroxybenzoyl)aminooctanoic acid.
14. The method of claim 12 , wherein the intracellular permeation enhancing agent is 6-Oxo-6-phenylhexanoic acid.
15. The method of claim 12 , wherein the intracellular permeation enhancing agent is 8-Cyclohexyl-8-oxooctanoic acid.
16. The method of claim 12 , wherein the intracellular permeation enhancing agent is 8-(2,5-Dichlorophenyl)-8-oxooctanoic acid.
17. The method of claim 12 , wherein the intracellular permeation enhancing agent is 7-Cyclohexyl-7-oxoheptanoic acid.
18. The method of claim 12 , wherein the therapeutic agent is a platinum agent.
19. The method of claim 12 , wherein the therapeutic agent is cisplatin.
20. The method of claim 12 , wherein the therapeutic agent is a vinca alkaloid agent.
21. The method of claim 12 , wherein the therapeutic agent is vinblastine.
22. The method of claim 12 , wherein the therapeutic agent is cisplatin and vinblastine.