Abstract: Embodiments of the disclosure concern methods and compositions related to preparation and use of combinatorial immunotherapies. In specific embodiments, compositions comprising 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 NK cells and the antibodies in which the antibody is bound to the NK cells and may also bind to another antigen, such as on a cancer cell.

Abstract: Embodiments of the disclosure concern methods and compositions related to optimization of selection of cord blood units to produce immune cells, such as NK cells, for adoptive cell therapy use. In specific embodiments, particular characteristics of the cord blood units and/or characteristics of cells derived therefrom are analyzed. When a threshold measurement for one or more characteristics is met for the cord blood unit(s) and/or characteristics of cells derived therefrom, the cord blood unit(s) are utilized as a source for production of immune cells. Specific characteristics for measurement include cord blood cell viability, total nuclear cell recovery, and nucleated red blood cell content, each prior to cryopreservation, and optionally cytotoxicity and/or expansion of immune cells subsequent to cryopreservation.

Abstract: Embodiments of the disclosure includes methods of producing viral-specific therapy (VST) cells specific for the SARS-CoV-2 virus and uses of the cells. The methods may utilized peptide mixtures and stimulation of mononuclear cells using particular cytokine cocktails. The cells may also be genetically modified to lack expression of one or more endogenous genes, including one or more genes that renders the cells more effective and/or able to withstand deleterious conditions, such as the presence of glucocorticoids.

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 B cells. The disclosure concerns large-scale processes for producing B cells that are 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.

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: 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.

Abstract: Embodiments of the disclosure include methods and compositions related to targeting of BCMA-expressing cells by NK cells specifically engineered to bind the BCMA antigen. In particular embodiments, NK cells that are manipulated to expressing BCMA-targeting chimeric antigen receptors (CARs) are utilized to target cancers that express BCMA. In certain embodiments, vectors that express the BCMA-targeting CARs also express particular suicide genes and/or particular cytokines.

Abstract: Provided herein are cryopreservation compositions and methods for cells of any kind, including for cells for adoptive cell therapy that are off-the-shelf cells. The cells for cryopreservation may be expanding NK cells expressing chimeric antigen receptors. In specific cases, the cryopreservation media comprises a cryoprotectant, such as DMSO, glycerol or hydroxyethol starch; serum or a non-serum alternative, such as platelet lysate; and one or more cytokines that are either natural, modified, synthetic, or recombinant.