US 12,226,522 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 lovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed on Jan. 11, 2024, as Appl. No. 18/410,900.
Application 18/410,900 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 2024/0240146 A1, Jul. 18, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A61K 9/00 (2006.01); A61K 35/17 (2015.01); A61K 38/20 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01)
CPC A61K 9/0019 (2013.01) [A61K 38/2013 (2013.01); A61K 39/4611 (2023.05); A61K 39/4644 (2023.05); 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)] 15 Claims
 
1. A method of administering tumor infiltrating lymphocytes (TILs) to a subject with endometrial cancer, wherein the method comprises:
(a) adding into a closed system a plurality of tumor fragments comprising a first population of TILs obtained by processing a sample of tumor tissue resected from the 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 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 (a) to step (b) occurs without opening the system;
(c) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional 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 second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (b) to step (c) occurs without opening the system;
(d) harvesting the third 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 third TIL population from step (d) to an infusion bag, wherein the transfer from step (d) to (e) occurs without opening the system;
(f) cryopreserving the infusion bag comprising the harvested TIL population from step (e) using a cryopreservation process; and
(g) administering a therapeutically effective dosage of the third population of TILs from the infusion bag in step (f) to the subject.