CPC C12N 5/0636 (2013.01) [A01N 1/0284 (2013.01); A61K 9/0019 (2013.01); A61K 31/675 (2013.01); A61K 31/7076 (2013.01); A61K 35/17 (2013.01); A61K 38/2013 (2013.01); A61P 35/00 (2018.01); C12N 5/0634 (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); 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)] | 30 Claims |
1. A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) performing a first expansion by (i) thawing cryopreserved dissociated tumor materials comprising a first population of TILs from a tumor that was resected from a subject with cancer, dissociated after the resection, and cryopreserved after the dissociation, and (ii) culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed system providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-14 days to obtain the second population of TILs;
(b) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for about 7-14 days to obtain the third population of TILs, wherein the second expansion is performed in the closed system providing a second gas-permeable surface area, and wherein the transition from step (a) to step (b) occurs without opening the closed system; and
(c) harvesting the third population of TILs, wherein the harvested third population of TILs is a therapeutic population of TILs, and wherein the transition from step (b) to step (c) occurs without opening the closed system.
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