Pharmaceutical composition and methods comprising immune cells and ponatinib
Methods and compositions for treating cancer are disclosed. The compositions comprise immune cells pretreated with ponatinib, or immune cells co-administered with ponatinib, where ponatinib promotes survival and anti-cancer cytotoxicity of the immune cells.
1. A pharmaceutical composition for treating cancer, the pharmaceutical composition comprising:
immune cells, wherein the immune cells comprise NK cells and/or T cells; and
ponatinib or a pharmaceutically acceptable salt or derivative thereof.
2. The pharmaceutical composition of claim 1 , wherein the immune cells comprise NK cells, wherein NK cells comprise at least one of NK cells cultured with cytokines; NK cells co-cultured with cytokines and irradiated human peripheral blood mononuclear cells (PBMC); NK cells co-cultured with established cell line(s) or genetically engineered feeder cells or both; and genetically engineered CAR-NK cells.
3. The pharmaceutical composition of claim 2 , wherein the established cell lines are transformed lymphocyte cells selected from LCL cells, KL-1 cells, or K562 cells.
4. The pharmaceutical composition of claim 1 , wherein the immune cells comprise T cells, wherein T cells comprise at least one of T cells isolated from peripheral blood mononuclear cells (PBMC) and cultured with cytokines; T cells extracted near tumors; T cells treated with activators; and genetically engineered CAR-T cells.
5. The pharmaceutical composition of claim 1 , wherein the concentration of ponatinib or pharmaceutically acceptable salt or derivative thereof is from about 1 nM to 1 μM.
6. The pharmaceutical composition of claim 1 , wherein said immune cells are pre-treated with an effective amount of ponatinib or pharmaceutically acceptable salt or derivative thereof.
7. The pharmaceutical composition of claim 6 , wherein said immune cells are pre-treated with ponatinib or pharmaceutically acceptable salt or derivative thereof at a concentration of about 1 nM to 1 M.
8. The pharmaceutical composition of claim 1 , wherein the immune cells comprise NK cells.
9. A pharmaceutical composition for treating cancer, the pharmaceutical composition comprising immune cells, wherein the immune cells comprise NK cells and/or T cells, wherein the immune cells are expanded in vitro and then treated with an effective concentration of ponatinib or a pharmaceutically acceptable salt or derivative thereof, wherein the pharmaceutical composition comprises about 10 5 to about 10 11 of the immune cells that have been treated with the ponatinib or pharmaceutically acceptable salt or derivative thereof.
10. The pharmaceutical composition of claim 9 , wherein the immune cells comprise NK cells selected from the group consisting of at least one of:
genetically engineered CAR-NK cells;
NK cells cultured with cytokines;
NK cells co-cultured with cytokines and irradiated human peripheral blood mononuclear cells (PBMC);
NK cells co-cultured with an established cell line; and
NK cells co-cultured with genetically engineered feeder cells.
11. The pharmaceutical composition of claim 10 , wherein the established cell line is a transformed lymphocyte.
12. The pharmaceutical composition of claim 11 , wherein the transformed lymphocyte is selected from the group consisting of at least one of: LCL cells, KL-1 cells, and K562 cells.
13. The pharmaceutical composition of claim 9 , wherein the immune cells comprise T cells, wherein T cells comprise at least one of T cells isolated from peripheral blood mononuclear cells (PBMC) and cultured with cytokines; T cells extracted near tumors; T cells treated with activators; and genetically engineered CAR-T cells.
14. The pharmaceutical composition of claim 9 , wherein the effective concentration of ponatinib or a pharmaceutically acceptable salt or other derivative thereof is about 1 nM to 1 μM.
15. The pharmaceutical composition of claim 9 , wherein the immune cells comprise NK cells.
16. A method for treating cancer, comprising administering an effective amount of the pharmaceutical composition of claim 9 to a patient in need thereof.
17. A method for treating cancer, the method comprising:
proliferating immune cells in vitro before treating the immune cells with ponatinib or a pharmaceutically acceptable salt or derivative, wherein the immune cells comprise NK cells and/or T cells; and
administering an effective amount of a pharmaceutical composition comprising the treated immune cells to a patient, wherein the pharmaceutical composition comprises about 10 5 to about 10 11 treated immune cells per dose.
18. The method of claim 17 , further comprising collecting immune cells from a subject before treating the immune cells with ponatinib.
19. The method of claim 18 , wherein the subject is the patient.
20. The method of claim 17 , wherein administering the pharmaceutical composition comprises intravenously injecting the pharmaceutical composition.
21. The method of claim 17 , wherein the concentration of ponatinib or pharmaceutically acceptable salt thereof is about 1 nM to 1 μM.
22. The method of claim 17 , wherein the pharmaceutical composition comprises about 10 5 to about 10 10 treated immune cells per dose.
23. The method of claim 17 , wherein the immune cells comprise NK cells.
24. The method of claim 17 , further comprising isolating the immune cells from peripheral blood.
25. The method of claim 17 , wherein the pharmaceutical composition further comprises ponatinib or a pharmaceutically acceptable salt or derivative thereof.