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.

Abstract: This disclosure describes a gate driver with voltage boosting capabilities. In some embodiments, the gate driver may comprise a charge pump that includes capacitor(s) and switch(es). Responsive a logic low input signal, the gate driver may bypass the capacitor(s) to allow the input digital signal to drive the gating signal directly. Conversely, responsive to a logic high input signal, the gate driver may couple the capacitor(s) in series with the input digital signal to generate a boosted gating signal. In some embodiments, the gate driver may comprise an inductor-capacitor resonant circuit to create a doubled output gating signal with respect to the input digital signal. In some embodiments, the resonant gate driver may include an additional voltage boosting capability that can be selectively enabled to compensate for a voltage drop during the signal transfer from the input to the output.

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 suppress alloreactive donor cells. 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 suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill transformed and infected cells. 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 immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: A transformer-based switching power converter can include a slew rate limiter coupled to the switching stage and configured to limit rate of change of voltage across one or more switching devices of the switching stage, thereby reducing voltage spikes appearing on the secondary winding. The slew rate limiter may be configured to selectively operate to limit rate of change of voltage across one or more switching devices of the switching stage during startup of the switching stage, upon waking from burst mode, or at any time when zero voltage switching of the one or more switching devices is unavailable. The slew rate limiter can include at least one circuit element configured to selectively alter a time constant of a gate drive circuit of at least one switching device in the switching stage to increase a turn-on transition time of the at least one switching device.

Abstract: This disclosure describes a flyback converter with a series-parallel mode (SPM) active clamp. The active clamp, coupled in parallel with the primary coil, may include a clamp switch, two or more snubber capacitors, and associated diodes. The active clamp may be configured to absorb and retain the leakage energy from the leakage inductance of the flyback converter. The clamp switch may be turned on selectively as the primary switch approaches one of a plurality peak values to adjust frequencies of the switching devices. With the active clamp circuit, the flyback converter may first re-capture the leakage energy in the active clamp circuit and then recover it back to the power source.

Abstract: A leakage energy steering circuit for a flyback converter can include a leakage energy steering capacitor and a leakage energy steering diode configured to be coupled between a first output terminal and a first secondary winding terminal of a flyback converter. The leakage energy steering circuit can further include a reset circuit having an impedance element and a diode configured to be coupled between a junction of the leakage energy steering capacitor and the leakage energy steering diode and a junction of a second secondary winding terminal and a second output terminal of the flyback converter. The impedance element may be a resistor or an inductor.

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: This disclosure describes a gate driver with voltage boosting capabilities. In some embodiments, the gate driver may comprise a charge pump that includes capacitor(s) and switch(es). Responsive a logic low input signal, the gate driver may bypass the capacitor(s) to allow the input digital signal to drive the gating signal directly. Conversely, responsive to a logic high input signal, the gate driver may couple the capacitor(s) in series with the input digital signal to generate a boosted gating signal. In some embodiments, the gate driver may comprise an inductor-capacitor resonant circuit to create a doubled output gating signal with respect to the input digital signal. In some embodiments, the resonant gate driver may include an additional voltage boosting capability that can be selectively enabled to compensate for a voltage drop during the signal transfer from the input to the output.