US 12,453,697 B2
Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy
Seth Wardell, Tampa, FL (US); and Maritza Lienlaf Moreno, Tampa, FL (US)
Assigned to Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Appl. No. 17/290,708
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
PCT Filed Nov. 4, 2019, PCT No. PCT/US2019/059718
§ 371(c)(1), (2) Date Apr. 30, 2021,
PCT Pub. No. WO2020/096988, PCT Pub. Date May 14, 2020.
Claims priority of provisional application 62/903,585, filed on Sep. 20, 2019.
Claims priority of provisional application 62/755,954, filed on Nov. 5, 2018.
Prior Publication US 2022/0090018 A1, Mar. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A61K 9/00 (2006.01); A61K 35/17 (2025.01); A61K 38/20 (2006.01); A61K 40/11 (2025.01); A61K 40/42 (2025.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01)
CPC A61K 9/0019 (2013.01) [A61K 38/2013 (2013.01); A61K 40/11 (2025.01); A61K 40/42 (2025.01); A61P 35/00 (2018.01); C12N 5/0638 (2013.01); C07K 16/2809 (2013.01); C12N 2501/2302 (2013.01); C12N 2502/11 (2013.01)] 22 Claims
 
1. A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs comprising:
(a) adding into a first closed container in a closed system a plurality of tumor fragments comprising a first population of TILs obtained by processing a sample of tumor tissue resected from a subject with cancer into the plurality of tumor fragments;
(b) performing a priming first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, optionally OKT-3, and optionally antigen presenting cells (APCs) to produce a second population of TILs, wherein the priming first expansion is performed in the first closed container comprising a first gas-permeable surface area, wherein the priming first expansion is performed for a first period of about 3 to 7 or 8 days to obtain the second population of TILs, wherein the second population of TILs is greater in number than the first population of TILs;
(c) performing a rapid second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, OKT-3, and APCs, to produce a third population of TILs, optionally wherein the number of APCs added in the rapid second expansion is at least twice the number of APCs added in step (b), wherein the rapid second expansion is performed for a second period of about 7 to 11 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the rapid second expansion is performed in a second closed container comprising a second gas-permeable surface area;
(d) harvesting the therapeutic population of TILs obtained from step (c); and
(e) transferring the harvested TIL population from step (d) to an infusion bag.