Abstract: The disclosure provides a method of treating or reducing the risk of developing an alloimmune condition or an autoimmune condition in a subject in need thereof. The method comprises (a) measuring CD83 in a population of immune cells from the subject, and (b) administering to the subject a CD83-targeted therapeutic.

Abstract: Disclosed herein are chimeric antigen receptor (CAR) polypeptides, which can be used with adoptive cell transfer to target and kill cancers, that comprise a co-stimulatory signaling region having a mutated form of a cytoplasmic domain of DAP10 that enhances CAR-T cell function, e.g. by reducing CAR-T cell exhaustion. Also disclosed are immune effector cells, such as ?? T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a tumor associated antigen-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed are artificial antigen presenting cells (aAPCs) and the use of said aAPC in the creation of a universal T cell potency assays; such assays comprising a) obtaining a population of cells comprising T cells (including, but not limited CD4+ T cells, CD8+ T cells, chimeric antigen receptor T cells, and/or a population of tumor infiltrating lymphocytes (TILs); b) culturing the population of T cells with a population of MHC class 1/MHC class II negative artificial antigen presenting cells (aAPC) comprising one or more membrane bound antigen binding molecules (such as, for example antigen binding molecule that specifically bind CD3, CD28, and/or 4-1BBL including, but not limited to antibodies, diabodies, nanobodies, and/or antibody fragments (including, but not limited to scFv) that specifically bind CD3, CD28, and/or 4-1BBL); and c) detecting cytolytic action of the T cells (such as, for example, by ELISpot, ELISA, 51Cr release, intracellular cytokine stain, or flow cytometry).

Abstract: A power converter can include an input PFC stage that receives a rectified input voltage coupled to a flyback stage including a center-tapped primary winding magnetically coupled to a secondary winding and a main switch coupled in series with the primary winding. The output of the PFC stage can be coupled to the center tap of the primary winding, and an output of the power converter can be coupled to the secondary winding of the flyback stage. The converter can further include control circuitry coupled to the main switch and an auxiliary switch in the PFC stage that operates the main switch to regulate an output voltage of the power converter, selectively enables the auxiliary switch responsive to a low line voltage condition at the input of the power converter, and operates the enabled auxiliary switch synchronously with the main switch.

Abstract: Disclosed herein are methods and compositions relating to the resistance of adoptive immunotherapy caused by the induction of iNOS in tumor associated macrophage.

Abstract: Particular interest has arisen regarding the therapeutic potential of regulatory T cells (Tregs) in ischemic stroke. However, the ex vivo-expansion of Tregs usually takes several weeks to achieve a target number of cells. Allogeneic (off-the-shelf) Tregs would be desirable, but are limited by acute graft-versus-host disease (GVHD). As disclosed herein, CD83 is differentially expressed on alloreactive T cells. Therefore, disclosed herein are immune effector cells genetically modified to express a chimeric antigen receptor (CAR) polypeptide targeting CD83 that are capable of suppressing this alloreactivity. In some embodiments, the immune effector cell is used in combination with an autologous Treg therapy. In other embodiments, the autologous Treg is itself genetically modified to express the CAR polypeptide targeting CD83.

Abstract: Bi-specific CAR-T cells are disclosed for treating NSCLCs. The disclosed CAR-T cells contain CAR polypeptides that can bind EGFR/MUC1-expressing cells. Therefore, also disclosed is an immune effector cell genetically modified to express an anti-EGFR CAR binding agent and an anti-MUC1 binding agent. Also disclosed are methods of providing an anti-tumor immunity in a subject with a EGFR and MVUC1-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to suppress alloreactive donor cells. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed regulatory T cells engineered to express the disclosed CARs. Also disclosed is a method of preventing rejection of off-the-shelf therapeutic immune effector cells, such as CAR-T cells, in a subject that involves administering to the subject an effective amount of a regulatory T cell genetically modified with a disclosed CD83-specific CAR.

Abstract: Disclosed are compositions and methods for targeted treatment of myeloid and B cell malignancies. In particular, chimeric antigen receptor (CAR) T cells are disclosed that can be used with adoptive cell transfer to target and kill myeloid and B cell malignancies with reduced antigen escape. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a myeloid and B cell malignancies that involves adoptive transfer of the disclosed CAR T cells.

Abstract: A power converter can include an input PFC stage that receives a rectified input voltage coupled to a flyback stage including a center-tapped primary winding magnetically coupled to a secondary winding and a main switch coupled in series with the primary winding. The output of the PFC stage can be coupled to the center tap of the primary winding, and an output of the power converter can be coupled to the secondary winding of the flyback stage. The converter can further include control circuitry coupled to the main switch and an auxiliary switch in the PFC stage that operates the main switch to regulate an output voltage of the power converter, selectively enables the auxiliary switch responsive to a low line voltage condition at the input of the power converter, and operates the enabled auxiliary switch synchronously with the main switch.

Abstract: A bi-specific genetically modified immune cell, comprising a first antigen binding moiety that is specific to CD83 and a second antigen binding moiety that is specific to interleukin 6 receptor (IL-6R). Also provided herein are uses of such bi-specific genetically modified immune cells for suppressing alloreactive donor cells in cell transplantation.

Abstract: Disclosed are compositions and methods for treating autoimmune diseases such as lupus, including immune cells expressing at least a chimeric antigen receptor (CAR) polypeptides that binds CD83 and uses thereof for suppressing and/or killing autoreactive cells in a subject having an autoimmune disease.

Abstract: Disclosed herein are methods of producing chimeric antigen receptor (CAR) T cells using substrates, such as artificial antigen presenting cells, containing on a surface a a heparin binding domain (HBD), anti-CD3 single chain antibodies, anti-CD28 single chain antibodies (scFv), and optionally anti-41BBL antibodies. Anti-CD3 and Anti-CD28 scFvs bind and activate expanding T cells ex vivo, while the Heparin Binding Domain binds the viral vector, thereby bringing the T cells into close proximity with virus for effective gene transfer. This is a less costly, renewable, modifiable, and efficacious alternative to coated beads and RetroNectin® for gene transfer.

Abstract: Disclosed herein are methods of producing chimeric antigen receptor (CAR) T cells using substrates, such as artificial antigen presenting cells, containing on a surface a a heparin binding domain (HBD), anti-CD3 single chain antibodies, anti-CD28 single chain antibodies (scFv), and optionally anti-41BBL antibodies. Anti-CD3 and Anti-CD28 scFvs bind and activate expanding T cells ex vivo, while the Heparin Binding Domain binds the viral vector, thereby bringing the T cells into close proximity with virus for effective gene transfer. This is a less costly, renewable, modifiable, and efficacious alternative to coated beads and RetroNectin® for gene transfer.

Abstract: Disclosed are compositions and methods for treating acute myeloid leukemia (AML) in subjects. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to treat AML. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of trating AML in a subject that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed are compositions and methods for suppressing without killing alloreactive and/or autoreactive lymphocytes. The methods can be used for preventing graft versus host disease (GVHD) in subjects receiving donor cells or treating autoimmunity. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to suppress alloreactive or autoreactive lymphocytes. Also disclosed are regulatory T cells that are engineered to express these CARs. Therefore, also disclosed are methods of suppressing alloreactive or autoreactive lymphocytes in a subject in need thereof that involves adoptive transfer of the disclosed regulatory T cells engineered to express the disclosed CARs.

Abstract: Disclosed herein are chimeric antigen receptor (CAR) polypeptides, which can be used with adoptive cell transfer to target and kill cancers, that comprise a co-stimulatory signaling region having a mutated form of a cytoplasmic domain of CD28 that enhances CAR-T cell function, e.g. by reducing CAR-T cell exhaustion. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a tumor associated antigen-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed herein are methods of expanding immune cells for immunotherapy and/or increasing the purity of a population of CAR T cells using artificial antigen presenting cells (aAPCs) having on their surface NKG2D ligand (such as for example MICA, MICB, RAET1E/ULBP4, RAET1G/ULBP5, RAET1 H/ULBP2, RAET1/ULBP1, RAET1UULBP6, and/or RAET1N/ULBP3 as well as mouse ligands H60, MULT-1, and Rae-1) and/or antibodies that bind NKG2D (including, but not limited to antibody fragments, such as, for example, F (ab?)2, Fab?, Fab, and/or scFv).

Abstract: Disclosed herein are methods of expanding immune cells for immunotherapy and/or increasing the purity of a population of CAR T cells using an immune and/or magnetic bead; wherein the beads comprises Protein L on its surface. The disclosed beads can also comprise antibodies that bind molecules of the T cell inhibitory pathway. For example, anti-CD3 scFv on the surface of the beads can bind and activate T cells, while anti-CD28 scFv and 4-1BBL on the surface of the beads can provide dual co-stimulation for the T cells resulting in decreased levels of the markers CD25, TIM3, LAG3, and PD1. For example, blocking PD1/PDL1 ligation can limit suppression that is mediated by the tumor microenvironment. This is a less costly and more efficient alternative to peripheral blood mononuclear cells (PBMCs) and cytokine treatments that result in better quality T cell for adoptive transfer back into patients.

Abstract: Disclosed herein are methods of expanding immune cells for immunotherapy and/or increasing the purity of a population of CART cells using artificial antigen presenting cells (aAPCs) having on their surface Protein L. The disclosed aAPCs can also secrete antibodies that bind molecules of the T cell inhibitory pathway. For example, anti-CD3 scFv on the surface of the aAPCs can bind and activate T cells, while anti-CD28 scFv and 4-1BBL on the surface of the aAPCs can provide dual co-stimulation for the T cells resulting in decreased levels of the markers CD25, TIM3, LAG3, and PD1. For example, blocking PD1/PDL1 ligation can limit suppression that is mediated by the tumor microenvironment. This is a less costly and more efficient alternative to peripheral blood mononuclear cells (PBMCs) and cytokine treatments that result in better quality T cell for adoptive transfer back into patients.