Methods for activating and expanding TILs using unconventional cytokines are provided. These methods include techniques for activating and expanding TILs using streamlined approaches, including one-step approaches, approaches using agonists for stimulation, approaches more suitable for clinical manufacturing, and approaches without the requirement of feeder cells, are provided. Compositions of expanded populations of TILs are also provided, in addition to populations of expanded TILs enriched in central memory T cell phenotype.

Provided is an engineered T cell. The expression level of an HLA class I molecule on the surface of the T cell is down-regulated to 10-50% of that of a non-engineered T cell. The expression of the T cell down-regulates a functional protein of the HLA class I molecule. The functional protein down-regulates at least one of HLA-A, HLA-B, and HLA-E molecules of the HLA class I molecule. The T cell may be an allogeneic CAR-T cell. Also provided is an application of the T cell or the allogeneic CAR-T cell.

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 disclosure provides systems for inducing activity of immune cells and methods of immunotherapy. Systems of the present disclosure for inducing immune cell activity comprise a chimeric antigen receptor, a T cell receptor, and various combinations thereof.

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 invention relates to a method of expanding and generating a population of cytokine-induced killer (CIK) cells from peripheral blood mononuclear cells comprising steps of a) separating the mononuclear cells from the peripheral blood; b) transferring the separated mononuclear cells into a culture medium; c) adding cytokines into the culture medium to induce expansion and generation of the CIK cells; and d) obtaining the expanded and generated population of CIK cells.

The disclosure provides compositions and method that promote adoptive cellular therapy. The disclosure provides polynucleotides, vectors, systems and cells comprising chimeric antigen receptors (CARs), synthetic immune receptors (SIRs), and the like in combination the specific activators of NFkB activity, thus improving cellular proliferation, expression and reduced apoptosis, which improves cell persistence in adoptive cell therapy.

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.