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AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorMarco L. Davila
Estimating the term…
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 CD28 that enhances CAR-T cell function, a mutated form of a cytoplasmic domain of 41BB that enhances nuclear factor kappaB (NFκB) signaling, or a combination thereof. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Also disclosed are immune effector cells co-expressing a CAR and one or more TRAF proteins. 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.
A chimeric antigen receptor (CAR) polypeptide, comprising a tumor associated antigen (TAA) 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 41BB that enhances nuclear factor kappaB (NFκB) signaling, a mutated form of a cytoplasmic domain of CD28 that enhances CAR-T cell fusion, or a combination thereof.
An immune effector cell, co-expressing a heterologous chimeric antigen receptor (CAR) polypeptide and one or more TRAF proteins.
The immune effector cell of claim 16 or 17, wherein the CAR comprises the recombinant polypeptide of any one of claims 1 to 9.
Dependencies are inferred from the claim text.