US 11,903,968 B2
Engineered immune cells resistant to tumor microenvironment
Philippe Duchateau, Draveil (FR); Anne-Sophie Gautron, Etrechy (FR); Laurent Poirot, Paris (FR); and Julien Valton, New York, NY (US)
Assigned to CELLECTIS, Paris (FR)
Appl. No. 16/629,506
Filed by CELLECTIS, Paris (FR)
PCT Filed Jul. 20, 2018, PCT No. PCT/EP2018/069734
§ 371(c)(1), (2) Date Jan. 8, 2020,
PCT Pub. No. WO2019/016360, PCT Pub. Date Jan. 24, 2019.
Claims priority of provisional application 62/535,448, filed on Jul. 21, 2017.
Claims priority of application No. PA201770603 (DK), filed on Aug. 7, 2017.
Prior Publication US 2021/0128613 A1, May 6, 2021
Int. Cl. C12N 5/00 (2006.01); A61K 35/17 (2015.01); A61K 39/395 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); C12N 15/113 (2010.01)
CPC A61K 35/17 (2013.01) [A61K 39/39541 (2013.01); C07K 16/2818 (2013.01); C12N 5/0636 (2013.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01); C12N 2510/00 (2013.01)] 9 Claims
 
1. An engineered immune cell,
wherein said engineered immune cell has been genetically modified by intracellular expression of a rare-cutting endonuclease selected from a TALEN, RNA-guided endonuclease, ZFN, meganuclease, and megaTAL that cleaves an endogenous polynucleotide sequence encoding a SERCA3 protein to inactivate the expression of the SERCA3 protein encoded by the endogenous polynucleotide sequence and interrupt calcium transport and signaling,
wherein said engineered immune cell further expresses a chimeric antigen receptor (CAR), and
wherein the inactivation of the expression of the protein results in increased proliferation of the engineered immune cell at low glucose level.