The disclosure relates to delivery systems, and corresponding methods, for selecting and delivering an allogeneic T-cell line for administration to a patient, e.g., according to the HLA profile of the patient's somatic or diseased cells.

The presently disclosed subject matter provides novel T cell receptors (TCRs) that target an EWSR1/WT1 fusion protein. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with EWSR1/WT1 fusion protein.

Provided is a method for inducing CD4.sup.CD8.sup.+ T cells having an antigen specific cytotoxic activity from pluripotent stem cells, comprising the steps of: (1) differentiating pluripotent stem cells to give a cell culture comprising CD4.sup.CD8.sup. T cells and CD4.sup.+CD8.sup.+ T cells, (2) removing CD4.sup.CD8.sup. cells from the cell culture obtained in step (1), and (3) differentiating the CD4.sup.+CD8.sup.+ cells in the cell culture into CD4.sup.CD8.sup.+ T cells.

The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

The present invention relates to a method for activating helper T cells, which includes the step of activating helper T cells by adding a WT1 peptide to antigen presenting cells, wherein the WT1 peptide has the ability to bind to any MHC class II molecule of an HLA-DRB1*0101 molecule, an HLA-DRB1*0401 molecule, an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB1*0901 molecule, an HLA-DRB1*1101 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule or an HLA-DPB1*0301 molecule, and the like.

Provided herein, inter alia, are methods and compositions for engineering T cells. The methods include contacting a T cell with a nucleic acid and one or more cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway inhibitors. The methods provided herein are contemplated to increase cell viability, expansion and gene editing efficiency, thereby allowing an increase in the total number of engineered T cells.

The present invention relates generally to a population of stem cells (e.g., iPSCs or HSCs) that comprise nucleic acids encoding a T cell receptor and a chimeric antigen receptor directed to multiple distinct antigenic determinants, for example two distinct tumour antigenic determinants. The present invention is also directed to a population of T cells that co-express a T cell receptor and a chimeric antigen receptor directed to multiple distinct antigenic determinants, such as two distinct tumour antigenic determinants. The cells of the present invention can be derived from chosen donors whose HLA type is compatible with significant sectors of the populations, and are useful in a wide variety of applications, in particular in the context of the therapeutic treatment of neoplastic conditions.

The present disclosure provides T cell receptors (TCRs) and related binding proteins with high functional avidity against tumor associated antigen p37 from Wilms tumor protein 1 (WT1), T cells expressing such high affinity WT1 specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress WT1 and/or produce the p37 antigen, such as in cancer.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express an antigen-targeted chimeric antigen receptor and a prodrug converting enzyme for the treatment of inflammation, inflammatory diseases, or pathogenic infections.

The present invention provides co-cultures of organoids and immune cells, and methods of using these to identify agents for treating diseases.