The present disclosure provides feeder hydrogel particles that can function to support the growth, proliferation, and/or activation of a target cell in culture. The present disclosure also provides methods of culturing target cells with feeder hydrogel particles.

Provided herein are methods that relate, in some aspects, to the incubation or culturing, such as to induce stimulation of expansion (proliferation), activation, costimulation and/or survival, of a composition of cells, such as a population of lymphocytes. In some aspects, provided are methods and reagents for the stimulation, e.g., of expansion (proliferation), survival or persistence, activation, costimulation, or other effect, of cell populations that involve binding of agents to a molecule on the surface of the cells, thereby providing one or more signals to the cells. In some cases, the reagents are reagents containing a plurality of binding sites for agents, such as multimerization reagents, and thus the one or more agents are multimerized by reversibly binding to the reagent, e.g., thereby creating a stimulatory reagent (multimerized agent), having stimulatory agents multimerized thereon. In some aspects, the multimerized agent can provide for expansion or proliferation or other stimulation of a population of cells, and then such stimulatory agents can be removed by disruption of the reversible bond. Also provided are compositions, apparatus and methods of use thereof.

The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.

In some embodiments, compositions and methods re¬lating to isolated artificial antigen presenting cells (aAPCs) are dis¬closed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors com¬prise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

Aspects of the present disclosure are directed to methods and compositions for inducing the generation of cells capable of killing cancer associated fibroblasts at least in part through the generation of ex vivo expanded cord blood cells which are programmed to kill cancer associated fibroblasts. Certain aspects relate to generation of immune cells, including T cell and Natural Killer (NK) cells, for use in targeting cancer cells and cancer associated fibroblasts. Further aspects are directed to gene editing and/or gene silencing of immune checkpoint proteins in therapeutic immune cells.

The present invention relates to an exosome for stimulating T cells and the pharmaceutical use thereof. Immune exosomes secreted from artificial antigen-presenting cells which express HLA, CD32, and co-stimulatory molecules CD32, CD80, CD83, and 4-1BBL are used to stimulate naive CD8+ T cells whereby preventive and therapeutic effects on tumors, pathogen infections, or autoimmune diseases can be provided.

The present invention relates generally to the treatment of PML by infusion of activated and expanded autologous lymphocytes.

Disclosed herein are cells that are immunoinhibitory cell, which cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the cell. In certain embodiments, the immunoinhibitory cell is a regulatory T cell. In another aspect, provided herein is a regulatory T cell that recombinantly expresses a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response. The cells can be sensitized to an antigen that is the target of a pathologic immune response associated with an immune-mediated disorder. Additionally provided are methods of using such cells to treat an immune-mediated disorder in a subject in need thereof.

The present invention provides compositions and methods for activation and expansion of T cells using a biocompatible solid substrate with tunable rigidity. Rigidity of a substrate is an important parameter that can be used to control the overall expansion and differentiation of T cells.

The present disclosure provides soluble mutant PD-L1 peptides, polynucleotides and vectors encoding the peptides, and methods of using the peptides to elicit differentiation of regulatory T cells.