Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy
The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.
1. A tumor infiltrating lymphocyte (TIL) pharmaceutical composition comprising:
i) an expanded population of tumor infiltrating lymphocytes (TILs), and
ii) a pharmaceutically acceptable carrier;
wherein the expanded population of TILs is capable of exhibiting increased IFN-γ secretion by at least one-fold in vitro as compared to a non-expanded population of TILs.
2. The composition of claim 1 , wherein the composition further comprises a cryopreservant.
3. The composition of claim 1 , wherein the composition is free of human serum.
4. The composition of claim 1 , wherein the composition further comprises 1% human serum albumin (HSA).
5. The composition of claim 2 , wherein the composition further comprises 1% human serum albumin (HSA) and the cryopreservant is dimethylsulfoxide.
6. The composition of claim 1 , wherein the expanded population of TILs is capable of increasing IFN-γ at least two-fold to at least five-fold in vitro.
7. A container comprising the composition of claim 1 .
8. The container of claim 7 , wherein the container is a bag.
9. The container of claim 7 , wherein the container is an infusion bag.
10. The composition of claim 6 , wherein the expanded population of TILs is capable of increasing IFN-γ at least two-fold in vitro.
11. The composition of claim 6 , wherein the expanded population of TILs is capable of increasing IFN-γ at least three-fold in vitro.
12. The composition of claim 6 , wherein the expanded population of TILs is capable of increasing IFN-γ at least four-fold in vitro.
13. The composition of claim 6 , wherein the expanded population of TILs is capable of increasing IFN-γ at least five-fold in vitro.
14. A tumor infiltrating lymphocyte (TIL) pharmaceutical composition comprising:
i) an expanded population of tumor infiltrating lymphocytes (TILs), and
ii) a pharmaceutically acceptable carrier;
wherein the expanded population of TILs is capable of exhibiting IFN-γ secretion greater than 200 pg/ml.
15. The composition of claim 14 , wherein the composition further comprises a cryopreservant.
16. The composition of claim 14 , wherein the composition is free of human serum.
17. The composition of claim 14 , wherein the composition further comprises 1% human serum albumin (HSA).
18. The composition of claim 15 , wherein the composition further comprises 1% human serum albumin (HSA) and the cryopreservant is dimethylsulfoxide.
19. The composition of claim 14 , wherein the IFN-γ secretion is greater than 1000 pg/ml.
20. A container comprising the composition of claim 14 .
21. The container of claim 20 , wherein the container is a bag.
22. The container of claim 20 , wherein the container is an infusion bag.
23. An expanded population of tumor infiltrating lymphocytes (TILs) that is capable of exhibiting IFN-γ secretion greater than 200 pg/ml.
24. The expanded population of TILs of claim 23 that is capable of exhibiting IFN-γ secretion greater than 1000 pg/ml.
25. An expanded population of tumor infiltrating lymphocytes (TILs) that is capable of exhibiting increased IFN-γ secretion by at least one-fold in vitro as compared to a non-expanded population of TILs.
26. The expanded population of TILs of claim 25 that is capable of increasing IFN-γ at least two-fold to at least five-fold in vitro.
27. The expanded population of TILs of claim 26 that is capable of increasing IFN-γ at least two-fold in vitro.
28. The expanded population of TILs of claim 26 that is capable of increasing IFN-γ at least three-fold in vitro.
29. The expanded population of TILs of claim 26 that is capable of increasing IFN-γ at least four-fold in vitro.
30. The expanded population of TILs of claim 26 that is capable of increasing IFN-γ at least five-fold in vitro.