Disclosed are improved methods for manufacturing large-scale populations of robust, highly pure, and functional T regulatory cells (Tregs). Also disclosed are expanded Treg populations, cryopreserved Treg populations and methods and uses of these cells in compositions formulated for treating one or more mammalian diseases, including, for example, treatment, prophylaxis, and/or amelioration of one or more symptoms of a human neurodegenerative disorder. In particular, the compositions and methods provided herein find clinical use in the treatment and amelioration of one or more symptoms of amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and other neurological diseases and disorders.

Regulatory T cells (T.sub.reg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4.sup.+ T.sub.reg cells have been described—naturally occurring T.sub.reg cells and adaptive T.sub.reg cells. Disclosed herein are methods for producing efficacious CAR T.sub.reg cells in a GMP-scalable system.

Provided are a novel compound having CDK8 and/or CDK19 inhibitory activity, and a production method for Tregs. The treatment of T cells with a CDK8 and/or CDK19 inhibitor induces Foxp3 in the T cells. Foxp3.sup.+ T cells can be induced by treating Foxp3.sup.− T cells with the CDK8 and/or CDK19 inhibitor in vitro. Thus, Tregs can be induced.

Provided herein are combinations of an IL-2 molecule or mutein and a TNFR agonist, and complexes comprising IL-2/TNFR agonist molecules, such as Fc-bound IL-2/TNFR agonist molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

The present invention relates to chimeric receptors (e.g. CARs including both single chain and multichain CARs) that bind to TREM2 ligands and their use in therapy. In particular, the invention provides a chimeric receptor comprising: (a) an exodomain comprising the ligand binding domain of TREM2 or a functional variant thereof, optionally wherein said exodomain is resistant to cleavage by a sheddase; (b) a transmembrane domain; and (c) an endodomain comprising an intracellular signalling domain.

A method for expanding a population of γδ T-cells is provided in which isolated activated Peripheral Blood Mononuclear Cells (PBMCs) are cultured in a medium comprising transforming growth factor beta (TGF-β) under conditions in which the production of effector γδ T-cells having therapeutic activity against malignant disease is favored. The use of TGF-β in the production of effector cells in particular Vγ9Vδ2 T-cells is also described and claimed.

A vector comprising a first polynucleotide encoding a FOXP3 polypeptide and a second polynucleotide encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen recognition domain which specifically binds to a human leukocyte antigen (HLA), wherein the first polynucleotide and the second polynucleotide are operably linked to the same promoter, and wherein the first polynucleotide is upstream of the second polynucleotide.

The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.

The present invention relates to a method for effectively proliferating regulatory T cells, by which, particularly, in the presence of a fusion protein dimer comprising IL-2 protein or a variant thereof and CD80 protein or a fragment thereof, CD4+, CD25+, and CD127− T cells can be effectively proliferated. In particular, when combined with a predetermined cell culture medium, regulatory T cells such as CD4+, CD25+, and CD127− can be effectively and specifically proliferated. In addition, when the method is used, it has been confirmed that the survival rate of regulatory T cells is remarkably increased as compared to a conventionally used culture method using IL-2, and a significant increase in the yield of Foxp3+ regulatory T cells has been confirmed. Thus, such a proliferation method can be used in the field of cell therapeutic agents using regulatory T cells.

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), for example.