US 12,031,157 B2
Closed process for expansion and gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy
Cecile Chartier-Courtaud, Palo Alto, CA (US); and Krit Ritthipichai, Tampa, FL (US)
Assigned to Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed on Jul. 1, 2022, as Appl. No. 17/810,537.
Application 17/810,537 is a continuation of application No. 17/387,357, filed on Jul. 28, 2021, granted, now 11,384,337.
Application 17/387,357 is a continuation of application No. 17/050,552, previously published as PCT/US2019/029286, filed on Apr. 26, 2019.
Claims priority of provisional application 62/680,821, filed on Jun. 5, 2018.
Claims priority of provisional application 62/663,885, filed on Apr. 27, 2018.
Prior Publication US 2022/0403334 A1, Dec. 22, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A01N 1/02 (2006.01); A61K 35/17 (2015.01); C12N 9/22 (2006.01); C12N 15/113 (2010.01)
CPC C12N 5/0638 (2013.01) [A01N 1/0221 (2013.01); A01N 1/0226 (2013.01); A61K 35/17 (2013.01); C12N 9/22 (2013.01); C12N 15/113 (2013.01); C12N 2310/20 (2017.05); C12N 2501/2302 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2501/515 (2013.01)] 30 Claims
 
1. A therapeutic population of tumor infiltrating lymphocytes (TILs) obtainable by a method comprising:
(a) adding tumor fragments processed from a tumor resected from a patient into a closed system to obtain a first population of TILs;
(b) performing a first expansion by 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 container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-12 days to obtain the second population of TILs, wherein the transition from step (a) to step (b) occurs without opening the system;
(c) performing a second expansion of the second population of TILs in a cell culture medium comprising 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 7-12 days to obtain the third population of TILs, wherein the third population of TILs comprises a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas permeable surface area;
(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; and
(e) at any time during the method, gene-editing at least a portion of the TILs.