US 12,280,140 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)
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed on Jan. 12, 2024, as Appl. No. 18/411,991.
Application 18/411,991 is a continuation of application No. 17/290,708, previously published as PCT/US2019/059718, filed on Nov. 4, 2019.
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 2024/0228963 A1, Jul. 11, 2024
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)] 12 Claims
 
1. A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) adding into a first closed container in a closed system 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 endometrial cancer into the plurality of tumor fragments;
(b) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed in the first closed container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3 to 11 days to obtain the second population of TILs;
(c) performing a second expansion by supplementing the cell culture medium with additional IL-2, OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed in a second closed container providing a second gas-permeable surface area, wherein the second expansion is performed for about 7 to 11 days in order to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, and wherein the transition from step (b) to step (c) occurs without opening the system;
(d) harvesting the therapeutic population of TILs obtained from step (c), wherein the transition from step (c) to step (d) occurs without opening the system;
(e) transferring the harvested therapeutic population of TILs from step (d) into an infusion bag, wherein the transition from step (d) to step (e) occurs without opening the system; and
(f) cryopreserving the infusion bag comprising the harvested TIL population from step (e) using a cryopreservation process.