Processes for production of tumor infiltrating lymphocytes and uses of 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. An expanded tumor infiltrating lymphocyte (TL) composition comprising:
i) a therapeutic population of tumor infiltrating lymphocytes (TILs), wherein said therapeutic population comprises expanded TILs, and
ii) a cryopreservant;
wherein the therapeutic population of TILs exhibits increased IFN-γ secretion by at least one-fold in vitro as compared to a non-expanded population of TILs.
2. The TIL composition of claim 1 , wherein the cryopreservant comprises DMSO.
3. The TIL composition of claim 1 , wherein the cryopreservant comprises 7% to 10% DMSO.
4. The TEL composition of claim 1 , wherein the cryopreservant is a cryopreservation medium.
5. The TIL composition of claim 4 , wherein the cryopreservation medium is CS10.
6. The TIL composition of claim 1 , wherein the composition is free of human serum.
7. The TIL composition of claim 1 , wherein the composition comprises 1% human serum albumin (HSA).
8. The TIL composition of claim 1 , wherein the composition is capable of increasing IFN-γ at least two-fold to at least five-fold in vitro.
9. The TIL composition of claim 1 , wherein the composition is capable of increasing polyclonality at least one-fold to at least five-fold as compared to an untreated patient.
10. The TIL composition of claim 1 , wherein about 1×10 9 to about 9×10 10 TILs are administered to a patient.
11. The TEL composition of claim 1 , wherein the composition is capable of increasing IP-10 and/or MCP-1 at least one-fold to at least five-fold as compared to an untreated patient.
12. The TL composition of claim 11 , wherein the increase in IP-10 is measured as an increase in the blood of the treated patient.
13. The TIL composition of claim 11 , wherein the increase in MCP-1 is measured as an increase in the blood of the treated patient.
14. A container comprising the TIL composition of claim 1 .
15. The container of claim 14 , wherein the container is a bag.
16. The container of claim 14 , wherein the container is a gas-permeable bag.
17. The container of claim 14 , wherein the container is an infusion bag.
18. The TIL composition of claim 8 , wherein the composition is capable of increasing IFN-γ at least two-fold in vitro.
19. The TIL composition of claim 8 , wherein the composition is capable of increasing IFN-γ at least three-fold in vitro.
20. The TIL composition of claim 8 , wherein the composition is capable of increasing IFN-γ at least four-fold in vitro.
21. The TIL composition of claim 8 , wherein the composition is capable of increasing IFN-γ at least five-fold in vitro.
22. The TIL composition of claim 1 , wherein the IFN-γ secretion is measured in vitro by enzyme-linked immunosorbent assay.