Provided herein are EMCN-specific antigen-binding domains, and chimeric proteins including the EMCN-specific antigen-binding. Also provided herein are cells, nucleic acids, vectors, compositions, and methods directed to proteins including the EMCN-specific antigen-binding domains.

The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor antigens. It relates to cells comprising: an antigen-recognizing receptor (e.g., a chimeric antigen receptor, a TCR, or a TCR like fusion molecule); and a gene disruption of a CD70 locus. The gene disruption of the CD70 locus can improve the activity and/or efficiency of the cells.

Engineered Treg-like cells, CD4.sup.LVFOXP3 T cells, and their use in cellular therapy to promote immune tolerance are disclosed. In particular, CD4.sup.LVFOXP3 T cells are produced by transduction of CD4.sup.+ T cells with a lentiviral vector expressing FOXP3 under the control of a constitutive promoter. Transduced cells express FOXP3 at high and persistent levels and acquire immune suppressive characteristics resembling naturally occurring Treg cells.

A bi-specific genetically modified immune cell, comprising a first antigen binding moiety that is specific to CD83 and a second antigen binding moiety that is specific to interleukin 6 receptor (IL-6R). Also provided herein are uses of such bi-specific genetically modified immune cells for suppressing alloreactive donor cells in cell transplantation.

Methods of generating an isolated population of non-graft versus host disease (GVHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation, are disclosed. Cells generated by the methods, pharmaceutical compositions and methods of treatment are also disclosed.

An example genetically engineered natural killer (NK) cell comprises an exogenous polynucleotide sequence that includes a receptor element, an actuator element, and an effector element. The receptor element encodes a chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain operably linked to a transmembrane domain, and an intracellular signaling domain, wherein the extracellular antigen binding domain recognizes a surface antigen of a target cell. The actuator element encodes a transcription factor binding site that upregulates synthesis of an effector protein. The effector element encodes the effector protein operably linked to a signal peptide, wherein, in response to the antigen binding domain of the CAR binding to the antigen of the target cell, the engineered NK cell is configured to activate and, to synthesize and secrete the effector protein.

The present disclosure provides materials and methods for the treatment of autoimmune diseases (including vitiligo).

The present invention provides a composition comprising A) immune cells such as T cells comprising a) an inducible gene expression system comprising I) a first nucleic acid comprising a drug-inducible promoter operably linked to a second nucleic acid, and II) said second nucleic acid encoding a polypeptide or a non-coding RNA (ncRNA) which decreases cell surface expression level of major histocompatibility complex (MHC) class I relative to cell surface expression level of MHC class I of an immune cell that does not express said polypeptide or ncRNA; and b) a third nucleic acid encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR); and B) a drug that induces said drug-inducible promoter. Preferentially, said polypeptide may be a viral protein which decreases cell surface expression level of major histocompatibility complex (MHC) class I relative to cell surface expression level of MHC class I of an immune cell that does not express the viral protein.

Chimeric autoantibody receptors (CAARs) can include separate signaling and recognition constructs that are able to bind ligands that target autoantigens made of conventional amino acids, non-conventional amino acids, carbohydrates, or nucleic acids. Additionally, the present disclosure describes cells modified to express such constructs and the use of such constructs and/or cells in the treatment of autoimmune disease.

Described herein are immunoresponsive cells which are useful for their preventive and therapeutic potential against autoimmune diseases and rejections of solid organ transplants.