CPC A61K 35/17 (2013.01) [A01N 1/0284 (2013.01); A61K 9/0019 (2013.01); A61K 31/675 (2013.01); A61K 31/7076 (2013.01); A61K 38/2013 (2013.01); A61K 39/4611 (2023.05); A61K 39/464499 (2023.05); A61P 35/00 (2018.01); C12N 5/0634 (2013.01); C12N 5/0636 (2013.01); C12N 5/0638 (2013.01); A61K 38/217 (2013.01); A61K 39/0011 (2013.01); A61K 2039/5154 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); A61K 2039/55533 (2013.01); A61K 2239/26 (2023.05); C12N 2501/04 (2013.01); C12N 2501/2302 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2501/24 (2013.01); C12N 2501/603 (2013.01); C12N 2502/11 (2013.01); C12N 2506/30 (2013.01)] | 13 Claims |
1. A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) obtaining a first population of TILs from a tumor resected from a subject by processing a tumor sample obtained from the subject into multiple tumor fragments;
(b) adding the tumor fragments into a closed system;
(c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising pegylated IL-2 to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-11 days to obtain the second population of TILs, and wherein the transition from step (b) to step (c) occurs without opening the system;
(d) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional pegylated IL-2, OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for about 7-11 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (c) to step (d) occurs without opening the system;
(e) harvesting the therapeutic population of TILs obtained from step (d), wherein the transition from step (d) to step (e) occurs without opening the system;
(f) transferring the harvested TIL population from step (e) to an infusion bag, wherein the transfer from step (e) to (f) occurs without opening the system; and
(g) cryopreserving the infusion bag comprising the harvested TIL population from step (f) using a cryopreservation process.
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