Abstract: Embodiments of the disclosure concern methods and compositions related to preparation and use of combinatorial immunotherapies. In specific embodiments, compositions comprising engineered NK cells prepared in a particular manner also include certain antibodies. These compositions are utilized for treatment, such as for cancer treatment. In particular embodiments, the compositions include complexes of the engineered NK cells and the antibodies in which the antibody is bound to the engineered NK cells and may also bind to another antigen, such as on a cancer cell.

Abstract: Aspects of the present disclosure include methods and compositions related to therapeutic immune cells having enhanced metabolic fitness. In certain aspects, polynucleotides encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism and, optionally, one or more antigen-specific receptors, are disclosed. In some aspects, disclosed are methods for enhancing the metabolic fitness of an immune cell comprising introducing into the immune cell a polynucleotide encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism. Cells (e.g., NK cells, T cells) expressing polynucleotides encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism and, optionally, one or more antigen-specific receptors are described. Also described are therapeutic methods using polynucleotides of the disclosure.

Abstract: Embodiments of the disclosure encompass particular chimeric antigen receptor constructs that comprise optionally a hinge, one of the CD28 transmembrane domain or the DAP10 transmembrane domain, DAP10 costimulatory domain, and CD3zeta. In particular embodiments, the chimeric antigen receptor is expressed by natural killer (NK) cells, and in some cases the NK cells are further modified, such as to express one or more cytokines and optionally a suicide gene.

Abstract: Embodiments of the disclosure include methods and compositions related to targeting of CD5-expressing cells with particular engineered receptors. In specific embodiments, NK cells are specifically engineered to bind the CD5 antigen using particular chimeric antigen receptor constructs. In certain embodiments, vectors that express the CD5-targeting CARs also express particular a suicide gene and/or one or more particular cytokines.

Abstract: Embodiments of the disclosure encompass methods and compositions for producing engineered natural killer (NK) cells. The disclosure concerns large-scale processes for producing NK cells that are engineered to have disruption of expression of one or more genes, such as using CRISPR, and also engineered express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process.

Abstract: Provided herein are methods for producing NK cells expressing chimeric antigen receptors and having no expression of CISH. Further provided are methods for treating diseases by administering the CAR NK cells.