US 12,291,724 B2
Tumor-infiltrating lymphocytes for adoptive cell therapy
Amod A. Sarnaik, Tampa, FL (US); Shari Pilon-Thomas, Tampa, FL (US); Mark McLaughlin, Tampa, FL (US); and Hao Liu, Tampa, FL (US)
Assigned to H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC., Tampa, FL (US); and UNIVERSITY OF SOUTH FLORIDA, Tampa, FL (US)
Filed by H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC., Tampa, FL (US); and UNIVERSITY OF SOUTH FLORIDA, Tampa, FL (US)
Filed on May 24, 2022, as Appl. No. 17/752,481.
Application 17/752,481 is a continuation of application No. 16/272,524, filed on Feb. 11, 2019, granted, now 11,518,980.
Application 16/272,524 is a continuation of application No. 15/126,436, abandoned, previously published as PCT/US2015/021759, filed on Mar. 20, 2015.
Claims priority of provisional application 61/973,002, filed on Mar. 31, 2014.
Claims priority of provisional application 61/955,970, filed on Mar. 20, 2014.
Prior Publication US 2022/0282215 A1, Sep. 8, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A61K 35/12 (2015.01); A61K 39/00 (2006.01); G01N 33/50 (2006.01)
CPC C12N 5/0636 (2013.01) [A61K 35/12 (2013.01); A61K 39/4611 (2023.05); A61K 39/46449 (2023.05); G01N 33/505 (2013.01); A61K 2239/57 (2023.05); C12N 2501/05 (2013.01); C12N 2501/056 (2013.01); C12N 2501/2302 (2013.01); C12N 2501/50 (2013.01); C12N 2501/998 (2013.01); C12N 2501/999 (2013.01)] 25 Claims
 
1. A method of producing ex vivo expanded tumor-infiltrating lymphocytes (TILs), the method comprising:
(a) culturing TILs from a subject in a two-step process comprising:
(i) a pre-rapid expansion (pre-REP) stage in a first culture medium in the presence of IL-2; and
(ii) culturing the TILs from step (i) in a rapid expansion (REP) stage in a second culture medium, comprising reagents different from reagents of the first culture medium, in the presence of IL-2 to produce expanded TILs; and
(b) adding a toll like receptor (TLR) agonist to one or more of the first culture medium and the second culture medium in an amount effective to improve the tumor-specificity of the expanded TILs, wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR3, and TLR9.