	US 12,343,380 B2
	Expansion of TILs utilizing AKT pathways inhibitors
Cecile Chartier-Courtaud, Palo Alto, CA (US); and Maria Fardis, San Carlos, CA (US)
Assigned to Iovance Biotherapeutics, Inc.
Appl. No. 17/290,639
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
PCT Filed Nov. 4, 2019, PCT No. PCT/US2019/059598 § 371(c)(1), (2) Date Apr. 30, 2021, PCT Pub. No. WO2020/096927, PCT Pub. Date May 14, 2020.
Claims priority of provisional application 62/756,031, filed on Nov. 5, 2018.
Prior Publication US 2022/0033775 A1, Feb. 3, 2022
Int. Cl. A61K 35/17 (2025.01); A61K 38/20 (2006.01); A61K 39/395 (2006.01); A61K 40/11 (2025.01); A61K 40/42 (2025.01); C12N 5/0783 (2010.01)

CPC A61K 38/2013 (2013.01) [A61K 39/3955 (2013.01); A61K 40/11 (2025.01); A61K 40/42 (2025.01); C12N 5/0638 (2013.01); C12N 2501/2302 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2501/515 (2013.01); C12N 2501/727 (2013.01); C12N 2501/999 (2013.01); C12N 2502/11 (2013.01)]

28 Claims

1. A method for preparing tumor infiltrating lymphocytes (TILs) for adoptive T-cell therapy, the method comprising a two-step process comprising:

(a) a pre-rapid expansion (pre-REP) stage by treating a tumor fragment with a first cell culture medium comprising interleukin 2 (IL-2), OKT-3 antibody, and one or more AKT pathway inhibitor (AKTi) comprising an AKT kinase inhibitor, an mTOR inhibitor, and/or an PI3K inhibitor to provide TILs;

(b) a rapid expansion (REP) stage by expanding the TILs from step (a) with a second cell culture medium comprising cell culture media, irradiated feeder cells, OKT-3 antibody, and IL-2 to provide an expanded number of TILs; and,