Provided herein are bedside systems and methods for performing customized cell-based therapies and treatments in a patient-connected, closed-loop continuous-flow manner, including cellular modifications and treatments, e.g., to produce chimeric antigen receptor-T (CAR-T) cells among other cellular modifications and treatments.

Upon administration of rAAV vectors the humoral immune response (neutralizing antibodies) is the first barrier that needs to be overcome. Surprisingly it was found that by using immunoadsorption for depletion of immunoglobulins from the blood (plasma), subjects can be highly efficiently treated with rAAV vectors, i.e. obtain highly efficient transduction after rAAV vector administration, in spite of the presence of high levels of nAb.

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), and compositions and reaction mixtures comprising the same.

Dialysis is enhanced by using nanoclay sorbents to better absorb body wastes in a flow-through system. The nanoclay sorbents, using montmorillonite, bentonite, and other clays, absorb significantly more ammonium, phosphate, and creatinine, and the like, than conventional sorbents. The montmorillonite, the bentonite, and the other clays may be used in wearable systems, in which a dialysis fluid is circulated through a filter with the nanoclay sorbents. Waste products are absorbed by the montmorillonite, the bentonite, and the other clays and the dialysis fluid is recycled to a patient's peritoneum. Using an ion-exchange capability of the montmorillonite, the bentonite, and the other clays, waste ions in the dialysis fluid are replaced with desirable ions, such as calcium, magnesium, and bicarbonate. The nanoclay sorbents are also useful for refreshing a dialysis fluid used in hemodialysis and thus reducing a quantity of the dialysis fluid needed for the hemodialysis.

A combined bio-artificial liver support system, includes branch tubes that are connected in sequence: a blood input branch tube, an upstream tail end of which is set as a blood input end, a first plasma separation branch tube comprising at least a first plasma separator, a non-biological purification branch tube comprising at least a plasma perfusion device and a bilirubin adsorber, a biological purification branch tube comprising at least a hepatocyte culture cartridge assembly, and a plasma return branch tube, a downstream tail end of which is set as a blood output end.

The presently disclosed subject-matter provides specific compositions, conjugates, device, kits and systems for depleting fibrinolytic agents from biological fluids. The presently disclosed subject-matter further relates to the resulting biological fluid products that are devoid in fibrinolytic activity, therapeutic methods and uses thereof. The conjugates comprise a particle, at least one linker and at least one amino acid, derivative thereof or analog thereof being at least one of 4-(aminomethyl)-cyclo-hexane-carboxylic acid (tranexamic acid), epsilon-amino caproic acid, lysine, cyclohexanecarboxylic acid and 4-methyl-cyclohexanecarboxylic acid. A plurality of different conjugates (e.g. differing in particle size or type of linker) can be used.

The present disclosure relates to devices for the extracorporeal treatment of a patient having a complement factor related disease. The devices are adapted to remove said complement factors from the blood or blood plasma of a patient in need. The disclosure further relates to extracorporeal circuits comprising such devices and methods for the treatment of a patient suffering from a complement factor related disease.

Dialysis is enhanced by using nanoclay sorbents to better absorb body wastes in a flow-through system. The nanoclay sorbents, using montmorillonite, bentonite, and other clays, absorb significantly more ammonium, phosphate, and creatinine, and the like, than conventional sorbents. The montmorillonite, the bentonite, and the other clays may be used in wearable systems, in which a dialysis fluid is circulated through a filter with the nanoclay sorbents. Waste products are absorbed by the montmorillonite, the bentonite, and the other clays and the dialysis fluid is recycled to a patient's peritoneum. Using an ion-exchange capability of the montmorillonite, the bentonite, and the other clays, waste ions in the dialysis fluid are replaced with desirable ions, such as calcium, magnesium, and bicarbonate. The nanoclay sorbents are also useful for refreshing a dialysis fluid used in hemodialysis and thus reducing a quantity of the dialysis fluid needed for the hemodialysis.

The invention provides a method and an apparatus or system for dialysis. The method and apparatus or system are useful for removing an undesirable protein-binding substance such as a toxin from a biological fluid such as blood or blood plasma. As such, the method and apparatus or system are useful for treating a subject in need of dialysis such as a subject suffering from hepatic disease. The methods feature a) dialyzing a biological fluid against a dialysis fluid containing an adsorber for a protein-binding substance to be removed through a semipermeable membrane, b) adjusting the dialysis fluid so that the binding affinity of the adsorber for the protein-bound substance to be removed is lowered and the substance to be removed passes into solution, and c) balancing the volume or flow of one or more fluids in the apparatus or system suitable for dialyzing a biological fluid containing a protein-binding substance to be removed. The apparatus or system features a) a biological fluid circuit (3); b) a dialysis fluid circuit (2); c) a means (4; 6; 7; 8; 9) for solubilizing the protein-binding substance to be removed; d) a dialysis, filtration or diafiltration device (5); e) a balancing system or apparatus suitable for balancing the volume or flow of one or more fluids in the apparatus or system suitable for dialyzing a biological fluid containing a protein-binding substance to be removed; and f) a dialysate regeneration unit.

This document provides bioartificial liver (BAL) devices. Methods for making and using BAL devices also are provided.