Provided are engineered cells for adoptive therapy, including T cells. Also provided are methods and compositions for engineering and producing the cells, compositions containing the cells, and method for their administration to subjects. In some embodiments, the cells, such as T cells, contain genetically engineered antigen receptors that specifically bind to antigens, such as a chimeric antigen receptor (CAR). In some embodiments, the cells, such as a CAR-expressing T cell, contains an agent that is capable of reducing an inhibitory effect by repressing and/or disrupting a gene in an engineered cell, such as a gene involved in inhibiting the immune response. In some embodiments, features of the cells and methods provide for increased or improved activity, efficacy and/or persistence.
