Abstract: Embodiments of the disclosure encompass compositions comprising immune effector cells, such as natural killer (NK) cells, where the cells comprise one or more exogenously provided interleukins (IL), and wherein the cell optionally comprises one or more engineered receptors. In specific embodiments, the IL is not IL-15, and is IL-12, IL-21, or both. The NK cells may be utilized for treatment of cancer of any kind, including at least glioblastoma.

Abstract: Embodiments of the disclosure encompass methods and compositions for producing engineered T cells. The disclosure concerns large-scale processes for producing T cells that may be engineered to have disruption of expression of one or more genes using CRISPR and also express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process. The T cells may or may not be viral-specific.

Abstract: Embodiments of the disclosure provide methods and compositions that facilitate cancer treatment including at least because they concern therapies that circumvent the tumor microenvironment. In specific embodiments, compositions are utilized for therapy that utilize NK cells that are protected from the direct inhibition of their activity (using TGF-beta inhibitors) and/or that are indirectly protected from TGF-beta (using integrin inhibitors). In specific embodiments, the NK cells have deficient expression and/or activity for TGF-beta Receptor 2 and/or glucocorticoid receptor.