Abstract: Aspects of the present disclosure are directed to immune cells comprising polynucleotides encoding genetically engineered receptors (e.g., chimeric antigen receptors, T-cell receptors) and having anti-CD20 antibodies (or fragments thereof) attached to their surface. Certain aspects are directed to preactivated and/or expanded natural killer cells having anti-CD20 antibodies (or fragments thereof) attached to their surface. Also disclosed are compositions comprising such cells, and methods for using such compositions to treat an individual having CD20-positive cancer. Further aspects encompass methods for cell preparation comprising culturing natural killer cells with cytokines (e.g., IL-12, IL-15, and/or IL-18) and incubating the cells with an anti-CD20 antibody.

Abstract: The present application provides BCMA targeting chimeric antigen receptor (CAR) comprising a BCMA binding region and an intracellular costimulatory domain derived from DAP10. Further provided are engineered immune effector cells (such as NK cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

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 include methods and compositions in which NK cells are modified by the hand of man to express the T-cell receptor and CD3 co-receptor on NK cells that do not naturally express them. Such modified NK cells work effectively with bispecific or multi-specific antibodies that are tailored to comprise anti-CD3 antibodies that bind the modified NK cells, thereby triggering signaling, activation, and cytotoxicity of target cells to which the antibodies also bind. Thus, the NK cells are specifically configured to be able to work effectively with Bispecific NK cell engagers (BiKEs) as well as Bispecific T cell Engagers (BiTEs).

Abstract: Embodiments of the disclosure concern systems, methods, and compositions related to identification of a suitable cell therapy for an individual in need thereof. A cell line is selected from a plurality of cell lines for suitability for an individual based on an algorithm and cell identification number that includes values for HLA matching and the frequency of reactive CD4 and CD8 cytotoxic T lymphocytes as measured by interferon-? and IL-2. Particular parameters for HLA matching and reactive frequencies are utilized to calculate points towards the cell identification number, and the cell line with the highest cell identification number may be utilized.

Abstract: Embodiments of the disclosure include methods and compositions related to targeting of TROP-2-expressing cells with particular engineered receptors. In specific embodiments, NK cells are specifically engineered to bind TROP-2 using particular chimeric antigen receptor constructs. In certain embodiments, vectors that express the TROP-2-targeting CARs also express a particular suicide gene and/or one or more particular cytokines.

Abstract: Embodiments of the present disclosure include methods and compositions related to CD70-targeting polypeptides. In certain aspects, anti-CD70 antibodies are disclosed. In some aspects, disclosed are chimeric receptors engineered to bind to CD70. Also disclosed are immune cell engagers comprising a CD70-binding region and one or more immune cell binding regions. Cells (e.g., NNK cells, T cells) expressing CD70-targeting peptides are described. Also described are therapeutic methods using polypeptides of the disclosure.

Abstract: Embodiments of the disclosure encompass methods and compositions that enhance adoptive cell therapy by preventing or at least reducing on-target off-tumor effects of adoptive cell therapy. The disclosure concerns an immune effector cells of any type that are engineered to express two separate chimeric molecules: an activating chimeric antigen receptor that activates the immune effector cell through costimulatory domains following binding to a first antigen, and an inhibitory chimeric antigen receptor that inhibits cell-mediated activation upon binding to a second antigen. In specific cases, the inhibitory chimeric antigen receptor prevents fratricide and exhaustion by inhibiting activation of the cell through the activating chimeric antigen receptor when the inhibitory chimeric antigen receptor binds a particular antigen, including one adopted by sibling engineered immune effector cells through trogocytosis.

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

Abstract: Aspects of the disclosure encompass systems, methods, and compositions for producing exosomes from mesenchymal stem cells and, optionally, loading said exosomes with one or more therapeutic agents. The systems, methods, and compositions may 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. The exosomes may be loaded with one or more therapeutic agents using electroporation. In specific aspects, the exosomes may be provided to an individual in need thereof, including in some cases where the individual in need thereof is an individual having a medical disorder for which the exosomes would be therapeutic.

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 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: 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.