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: Provided herein are methods of manufacturing clinical grade exosomes derived from mesenchymal stem cells (MSCs). Further provided are methods of loading the exosomes with therapeutic agents, such as siRNA. Also provided herein are methods of treating diseases by administering the clinical grade exosome.

Abstract: Embodiments of the disclosure include systems, methods, and compositions for producing megakaryocytes and platelets for recipient individuals in need thereof. The megakaryocytes and platelets are produced following co-culture of MSCs and CD34+ cells in media comprising stem cell factor, thrombopoietin, and IL-6, and wherein at least the CD34+ cells have a knock-in of HLA-E at the beta-2-microglobulin genomic locus, in specific embodiments. In some cases, ROCK inhibitors are utilized.

Abstract: Provided herein are methods of manufacturing clinical grade exosomes derived from mesenchymal stem cells (MSCs). Further provided are methods of loading the exosomes with therapeutic agents, such as siRNA. Also provided herein are methods of treating diseases by administering the clinical grade exosomes.

Abstract: Embodiments of the disclosure encompass systems, methods, and compositions for producing exosomes from primed mesenchymal stem cells that are expanded in the presence of IFN?, TNF?, IL-1?, and IL-17. The systems, methods, and compositions ay occur in an automated cell expansion system that allows for controllable parameters and from which cells and exosomes may be harvested at one or more times as part of a particular regimen. In specific embodiments, the exosomes may be provided to an individual in need thereof, including in some cases when the exosomes comprise one or more therapeutic agents.

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: Provided herein are chimeric antigen receptors (CARs) comprising a truncated EGFRvIII (Ev3) in the hinge region of the CAR and/or a humanized scFv. Further provided herein are immune cells expressing the CARs as well as methods of their use in the treatment of immune disorders.

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 include methods and compositions related to targeting of CD70-expressing cells with NK cells specifically engineered to bind the CD70 antigen. In particular embodiments, NK cells that are manipulated to expressing CD70-targeting engineered receptors, such as CARs, are utilized to target cancers that express CD70. In certain embodiments, vectors that express the CD70-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 mesenchymal stem/stromal cells (MSCs). The disclosure concerns large-scale processes for producing MSCs 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 improvements on cell therapies by allowing the cells to be more effective for cancer treatment, including in a solid tumor microenvironment. In specific cases, the cells are modified to have reduced or inhibited levels of expression of T-Cell Death Associated Gene 8 (TDAG8), such as by CRISPR gene editing. In specific cases, the cells are further modified to express, for example, one or more engineered receptors, one or more cytokines, and optionally a suicide gene.

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 tumor-infiltrating lymphocytes and/or engineered T cells that are protected from immunosuppression from the tumor microenvironment because they are engineered to have reduced or eliminated expression of transforming growth factor-beta receptor 2 and/or I-cell-Ig-and-ITIM-domain and/or CD7 genes.

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 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 methods for expanding NK cells expressing chimeric antigen receptors and/or T cell receptors. Further provided are methods for treating diseases by administering the CAR NK cells.

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.

Abstract: Provided herein are immune cells expressing antigenic receptors, such as a chimeric antigen receptor and a T cell receptor. Further provided herein are methods of treating immune-related disorder by administering the antigen-specific immune cells.