abstract |
The present invention provides chimeric antigen receptor (CAR) polypeptides, which may be used with adoptive transfer of cells to target and kill cancers, which comprise a costimulatory signaling region comprising a mutated form of a cytoplasmic domain of CD28 which improves T-cell (CAR-T) function, for example by reducing the depletion of T-Cells. The invention also relates to immune effector cells, such as T lymphocytes or natural killer (NK) cells, which are manipulated to express these CARs. Therefore, the invention also relates to methods of conferring anti-tumor immunity in a subject with an antigen-expressing cancer-associated tumor that involves adoptive transfer of the described immune effector cells manipulated to express the described CARs. |