Chimeric antigen receptors with mutated dap10 costimulatory domains
AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorMarco Davila
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Abstract
Disclosed herein are chimeric antigen receptor (CAR) polypeptides, which can be used with adoptive cell transfer to target and kill cancers, that comprise a co-stimulatory signaling region having a mutated form of a cytoplasmic domain of DAP10 that enhances CAR-T cell function, e.g. by reducing CAR-T cell exhaustion. Also disclosed are immune effector cells, such as γδ T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a tumor associated antigen-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.
Claims20
A chimeric antigen receptor (CAR) polypeptide, comprising a ligand binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, wherein the co-stimulatory signaling region comprises a mutated form of a cytoplasmic domain of DAP10, wherein the YINM subdomain has been substituted with a PRRP or PYAP subdomain.
A chimeric antigen receptor (CAR) polypeptide, comprising a ligand binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, wherein the co-stimulatory signaling region comprises a a cytoplasmic domain of DAP10 and wherein the intracellular signaling domain comprises the backbone of a DAP12 signaling domain comprising one or more heterologous ITAM subdomains.
Dependencies are inferred from the claim text.