Inhibitors of nfat and nfkb signaling for improving immune cell function
AssigneesMemorial Sloan Kettering Cancer Center, Sloan-Kettering Institute for Cancer Research, Memorial Hospital for Cancer and Allied Diseases
InventorsScott JAMES, Jacob S. FISCHMAN, Alexander P. BOARDMAN, Marcel VAN DEN BRINK
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Abstract
The present disclosure is directed to systems for inhibiting NFAT and/or NFkB signaling to improve the function of CAR expressing immune cells, e.g., CAR T cells. The system enables generation of immune cells engineered to express a CAR or multiple combinations of CARs (multi-CAR) and inhibitors of NFAT and/or NFkB signaling.
Claims27
A system comprising a plurality of nucleic acid constructs, wherein the plurality comprises:
- (a) a first nucleic acid construct encoding a membrane bound polypeptide comprising:
- (i) an extracellular domain comprising a first leucine zipper sequence;
- (ii) a transmembrane domain;
- and
- (iii) an intracellular domain;
- (b) a second nucleic acid construct encoding a soluble polypeptide comprising a second leucine zipper sequence capable of heterodimerizing with the first leucine zipper sequence and a signal peptide sequence;
- wherein each of the first and/or second nucleic acid constructs further encode one or more CAR, safety switch, switch receptor, and/or cytokine;
- and
- wherein the first or second nucleic acid construct further comprises a nucleic acid sequence encoding:
- (1) a nuclear factor of activated T cells (NFAT) inhibitor peptide or NFkB inhibitor peptide;
- and (2) a carrier protein.
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Dependencies are inferred from the claim text.