Lysosomal acid lipase and PPAR gamma ligands as immune therapies for cancer treatment
Methods of cancer treatment are disclosed. Particularly, disclosed herein are methods of administering LAL and PPARγ ligands for treating various cancer patients to promote anti-cancer immunity (suppress MDSC), use for inhibiting tumor progression, and use for inhibiting tumor metastasis.
1. A method for treating lung cancer in an individual in need thereof, the method comprising administering a therapeutically effective amount of lysosomal acid lipase (LAL) to the individual.
2. The method of claim 1 comprising administering LAL via an injection route selected from the group consisting of intramuscular, subcutaneous, intramedullary, intrathecal, intraventricular, intravenous, intravitreal, and combinations thereof.
3. The method of claim 1 wherein the LAL is administered as a pharmaceutical composition, the composition further comprising a pharmaceutically acceptable carrier.
4. The method of claim 1 further comprising administering a peroxisome proliferator-activated receptor gamma (PPARγ) ligand to the individual.
5. The method of claim 4 wherein the PPARγ ligand is selected from the group consisting of 9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), 15-deoxy-Delta12-14-prostaglandin (J2) (15d-PGD2), prostaglandin A1 (PGA1), prostaglandin A2 (PGA2), rosiglitazone (BRL49653), ciglitazone, pioglitazone, troglitazone, farglitazar, [[4-[2-(6-Benzoyl-2-oxo-3 (2H)-benzothiazolyl)ethoxy]phenyl]methyl]-1,3-propanedioic acid dimethyl ester (S26948), T0903131 (INT131) Besylate, and combinations thereof.
6. The method of claim 4 comprising administering the PPARγ ligand via an injection route selected from the group consisting of intramuscular, subcutaneous, intramedullary, intrathecal, intraventricular, intravenous, intravitreal, and combinations thereof.
7. The method of claim 4 wherein about 20 μmol/L of PPARγ ligand is administered to the individual.
8. The method of claim 1 wherein the administering step inhibits immune suppression in a tumor microenvironment.
9. The method of claim 1 wherein the administering step reduces the number and/or function of myeloid-derived suppressor cells in a tumor microenvironment.
10. A method of inhibiting tumor progression in an individual having lung cancer, the method comprising administering a therapeutically effective amount of lysosomal acid lipase (LAL) to the individual.
11. The method of claim 10 comprising administering LAL via an injection route selected from the group consisting of intramuscular, subcutaneous, intramedullary, intrathecal, intraventricular, intravenous, intravitreal, and combinations thereof.
12. The method of claim 10 wherein the administering step inhibits immune suppression in a tumor microenvironment.
13. The method of claim 10 wherein the administering step reduces the number and/or function of myeloid-derived suppressor cells in a tumor microenvironment.
14. A method for reducing lung cancer, liver cancer or melanoma tumor growth in an individual in need thereof, the method comprising administering a therapeutically effective amount of lysosomal acid lipase (LAL) in combination with a check point inhibitor to the individual.
15. The method of claim 14 wherein the check point inhibitor comprises PD-L1, PD-1 inhibitor, and combinations thereof.