US 11,866,731 B2
Modified immune cells and uses thereof
Weiyue Gu, Beijing (CN)
Assigned to CHINEO MEDICAL TECHNOLOGY CO., LTD, Beijing (CN)
Appl. No. 15/733,076
Filed by CHINEO MEDICAL TECHNOLOGY CO., LTD., Beijing (CN)
PCT Filed Nov. 12, 2018, PCT No. PCT/CN2018/115079
§ 371(c)(1), (2) Date May 8, 2020,
PCT Pub. No. WO2019/091478, PCT Pub. Date May 16, 2019.
Claims priority of application No. 201711101450.X (CN), filed on Nov. 10, 2017; application No. 201810017770.5 (CN), filed on Jan. 9, 2018; application No. 201810037682.1 (CN), filed on Jan. 16, 2018; application No. PCT/CN2018/090638 (WO), filed on Jun. 11, 2018; application No. PCT/CN2018/094126 (WO), filed on Jul. 2, 2018; and application No. PCT/CN2018/114897 (WO), filed on Nov. 9, 2018.
Prior Publication US 2020/0354676 A1, Nov. 12, 2020
Int. Cl. A61P 35/00 (2006.01); A61K 35/17 (2015.01); C07K 16/30 (2006.01); C12N 15/86 (2006.01); C12N 5/0783 (2010.01); C07K 14/725 (2006.01); C07K 16/28 (2006.01)
CPC C12N 5/0636 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 16/2803 (2013.01); C07K 16/30 (2013.01); C12N 15/86 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C12N 2740/15043 (2013.01)] 14 Claims
 
1. An isolated population of modified immune cells comprising modified immune cells that specifically binds to a tumor antigen,
wherein each modified immune cell comprises
a peripheral blood mononuclear cell (PBMC) expressing both
endogenous PD1 and
a chimeric stimulating molecule or a switch molecule, wherein said chimeric stimulating molecule or a switch molecule comprises:
an extracellular domain (ECD) of a protein that, in an unmodified immune cell, elicits an immune cell inactivation signal upon binding to its ligand, wherein said ECD is fused to an intracellular domain (ICD) of a co-stimulatory molecule that mediates an immune cell activation signal,
wherein binding of the chimeric stimulating molecule or the switch molecule to the ligand yields said immune cell activation signal in said modified immune cell instead of said immune cell inactivation signal and
wherein the isolated population comprises a higher concentration of PBMCs endogenously expressing PD1 compared to a population of PBMCs in a subject.