The present invention relates generally to immunotherapy, in particular immunotherapy for treating cancer, infectious diseases or autoimmune diseases. More specifically, the invention relates to Mucosal-Associated Invariant T (MAIT) cells expressing Chimeric Antigen Receptors (CARs), wherein the MAIT cell is allogenic with respect to the subject to be treated.

Some embodiments of the methods and compositions provided herein relate to modulating signaling of anti-hapten CAR T cells, such as anti-fluorescein CAR T cells, by the use or administration of an unconjugated hapten, such as unconjugated fluorescein or a salt or derivative thereof.

Provided are therapeutic agent including nucleic acid and CAR-modified immune cell and the use thereof. The therapeutic agent comprises first composition and second composition, the first composition comprises a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell; the labeling polypeptide has an extracellular antigen determining region, a spacer portion, and a transmembrane portion that are operatively linked, which can be expressed to form modification on the surface of the tumor cell and/or cancer cell; the extracellular antigen determining region comprises one or more epitope polypeptides; wherein, amino acid sequences of proteins on cell membrane or secreted proteins of mammal do not comprise the epitope polypeptide amino acid sequence in the natural state; the second composition comprises chimeric antigen receptor modified immune cell which specifically recognize and bind to the extracellular antigen determining region. The therapeutic agent achieves synergistic therapeutic effect.

Genetically modified cells, including a recombinant nucleic acid expression construct including a first nucleic acid sequence region encoding a chimeric antigen receptor (CAR) that includes an extracellular antigen-binding domain recognizing a carcinoembryonic antigen (CEA) protein, a second nucleic acid sequence region encoding a checkpoint inhibitory molecule, and a third nucleic acid sequence region encoding an immune stimulatory cytokine. In some aspects, the genetically modified cells are T cells or NK cells, preferably cytotoxic T lymphocytes. Anti-CEA CAR-T cells or anti-CEA CAR-NK cells preferentially recognize a membrane-bound CEA protein and express a checkpoint inhibitory molecule and/or an immune stimulatory interleukin in proximity to tumor tissue. Medical use of the cells may relate to treatment of a medical disorder associated with the presence of pathogenic cells expressing CEA, preferably cancer cells, more preferably cancer cells of solid malignancies.

Disclosed are compositions and methods for treating autoimmune diseases such as lupus, including immune cells expressing at least a chimeric antigen receptor (CAR) polypeptides that binds CD83 and uses thereof for suppressing and/or killing autoreactive cells in a subject having an autoimmune disease.

A method of generating a population of genetically modified veto cells is disclosed. The method comprising: (a) providing a population of cells comprising T cells, the T cells comprising at least 40% memory CD8.sup.+ T cells; (b) culturing the population of cells comprising T cells with an antigen or antigens under conditions which allow enrichment of tolerance-inducing antigen-specific cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being depleted of graft versus host (GVH) reactivity; and (c) transducing the cells with a polynucleotide encoding a heterologous cell surface receptor comprising a T cell receptor signaling module, thereby generating the population of genetically modified veto cells.

A method for performing gene editing on a target site in a cell, specifically a method for performing gene editing on a target site of a cell genome, comprising: (a) providing a cell to be genetically edited; (b) introducing into the cell (i) a gene editing enzyme or the encoding nucleic acid thereof or a first expression vector expressing the gene editing enzyme; and (ii) gRNA or a second expression vector expressing the gRNA, and performing gene editing on a target site of the cell genome, the gRNA directing the gene editing enzyme to perform fixed-point cutting on the target site; the targeting sequence of the gRNA targeting comprises one or more of the sequences shown in SEQ ID. No. 1-9. The method enables efficient gene editing to be performed on the target site.

The present disclosure provides compositions and methods for delivering a nucleic acid sequence encoding a chimeric antigen receptor (CAR) to an immune cell using a retroviral vector comprising an optimized Cocal vesiculovirus envelope protein.

A population of genetically engineered T cells, comprising a nucleic acid encoding an anti-CD83 CAR, a disrupted Reg1 gene, and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD83 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-β, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

The present disclosure provides hybrid promoter sequences comprising an MND promoter and HTLV enhancer capable of driving high levels of sustained expression of a heterologous sequence in immune cells, particularly Natural Killer (NK) cells. The disclosure also provides compositions comprising such vectors, immune cells which have been genetically modified to contain the vectors, as well as methods of using the same for inducing immune responses and treating cancer and other conditions.