Abstract: T cell manufacturing methods that co-culture T cells with autologous cell types to stimulate the T cells during manufacture are described. The T cells express a recombinant receptor. A binding domain expressed by the T cells binds an epitope on stimulating autologous cell types and/or an immune cell activating multi-specific binding molecule (e.g., a bi-specific antibody) during the co-culture. The methods can also allow for the expression of large transgenes by utilizing electroporation and transposons to deliver transgenes encoding the recombinant receptor. The disclosed methods create manufactured T cell populations with a high number of cells in comparison to starting cell numbers, a high percentage of recombinant receptor-expressing T cells within the cell number, and a beneficial naïve T cell marker profile.

Abstract: Some embodiments of the methods and compositions provided herein include methods and/or systems for increasing an activity of a cell comprising a chimeric antigen receptor (CAR), comprising use of a first nucleic acid encoding a transcription response element (TRE); and a second nucleic acid encoding a CAR, wherein the activity of the cell is increased compared to a cell lacking the first nucleic acid. In some embodiments, the increased activity of the cell is selected from: (i) survival of a subject administered the cell, wherein the subject comprises a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen; (ii) killing of a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen; and (iii) proliferation of the cell in the presence of a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen.

Abstract: Some embodiments of the methods and compositions provided herein relate to chimeric proteins comprising a programmed cell death protein 1 (PD 1) extracellular domain and an intracellular immunostimulatory domain. Some embodiments include a cell containing a PD 1 chimeric polypeptide and a chimeric antigen receptor (CAR). In some embodiments, the CAR comprises a ligand binding domain capable of specifically binding to a target antigen on a solid tumor. More embodiments relate to therapies to treat, inhibit or ameliorate certain disorders, such as a cancer, such as a solid tumor.

Abstract: A laparoscopic netting assembly is provided for conducting a gallbladder or bile duct procedure through one of the throughbores in a carrier sheath, which in turn may be positioned within a laparoscopic port. The carrier sheath includes at least one through channel for conducting a frame control rod, and optionally a deployment rod. The netting assembly includes a collapsible and expandable frame and a fluid permeable netting, which is preferably comprises a plurality of netting layers, suspended on the frame for collecting stones released from the gallbladder or bile duct. The frame is sized to also collect the gallbladder. The carrier sheath may also include one or more through channels for a cutting instrument.

Abstract: A device for the prevention or treatment of ulcers includes an absorbent layer 20 and an upper layer 30, 84 which may be transparent or opaque, and is preferably curved downward to engage the absorbent layer and minimize contact to the ulcer. A sensor or signaling member is provided for outputting an electrical signal in response to the flexible deformation of the upper layer indicative of the excessive pressure. A warning member, such as a light or alarm, is responsive to the signaling member for notifying the patient or caregiver of excessive pressure. In another embodiment, the device includes a plurality of shear detector sensors for outputting an electrical signal in response to shear movement between the absorbent layer and the patient's skin.