US 12,226,434 B2
Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
Seth Wardell, Tampa, FL (US); James Bender, Rancho Santa Margarita, CA (US); and Michael T. Lotze, Pittsburgh, PA (US)
Assigned to Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed on Jan. 12, 2021, as Appl. No. 17/147,096.
Application 17/147,096 is a division of application No. 15/863,634, filed on Jan. 5, 2018, granted, now 10,894,063.
Claims priority of provisional application 62/596,374, filed on Dec. 8, 2017.
Claims priority of provisional application 62/582,874, filed on Nov. 7, 2017.
Claims priority of provisional application 62/577,655, filed on Oct. 26, 2017.
Claims priority of provisional application 62/567,121, filed on Oct. 2, 2017.
Claims priority of provisional application 62/559,374, filed on Sep. 15, 2017.
Claims priority of provisional application 62/554,538, filed on Sep. 5, 2017.
Claims priority of provisional application 62/548,306, filed on Aug. 21, 2017.
Claims priority of provisional application 62/539,410, filed on Jul. 31, 2017.
Claims priority of provisional application 62/478,506, filed on Mar. 29, 2017.
Prior Publication US 2021/0128625 A1, May 6, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 35/26 (2015.01); A01N 1/02 (2006.01); A61K 9/00 (2006.01); A61K 31/675 (2006.01); A61K 31/7076 (2006.01); A61K 35/17 (2015.01); A61K 38/20 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C12N 5/00 (2006.01); C12N 5/078 (2010.01); C12N 5/0783 (2010.01); A61K 38/21 (2006.01)
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.