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.
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