Abstract: The present invention provides a method of identifying a target for preparing an inhibitory chimeric antigen receptor (iCAR) or a protective chimeric antigen receptor (pCAR) capable of preventing or attenuating undesired activation of an effector immune cell. Also provided are a list of iCAR targets, as well as vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: Provided herein are cell-distancing devices that protect cells that comprise them against host immune response when administered in a host. The disclosed cell-distancing devices engage with host immune cells and reduce their activity against cells that comprise the devices. Compositions of cell-distancing devices, cells comprising cell-distancing devices, and method of making and using such compositions are disclosed herein.

Abstract: The present invention provides a method of identifying a target for preparing an inhibitory chimeric antigen receptor (iCAR) or a protective chimeric antigen receptor (pCAR) capable of preventing or attenuating undesired activation of an effector immune cell. Also provided are a list of iCAR targets, as well as vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: Provided herein are novel blocking chimeric antigen receptors (“bCARs”) and immune cells (e.g., effector and regulatory immune cells) that express such bCARs. Such blocking CARs prevent undesired activation of the immune cells, particularly undesired activation of the immune cells against normal tissue in therapeutic applications. Thus, such bCARs advantageously allow for selective immune cell activation only upon interaction with specific target cells (e.g., tumor cell).

Abstract: A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (iCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: A synthetic nucleic acid expression system for production of a transcript of interest in a predefined cell-state is provided, the system comprising (a) a first nucleic acid sequence comprising a first promoter operably linked to a nucleic acid sequence encoding a first trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 5? fragment of said transcript of interest and a first RNA sequence required for spliceosome-dependent trans-splicing; and (b) a second nucleic acid sequence comprising a second promoter operably linked to a nucleic acid sequence encoding a second trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 3? fragment of said transcript of interest and a second RNA sequence required for spliceosome-dependent trans-splicing; wherein said first promoter and said second promoter are different and each one is specifically regulated by said predefined cell-state.

Abstract: A nucleic acid molecule encoding an activating chimeric antigen receptor (aCAR) comprising at least one signal transduction element derived from CD40 is provided.

Abstract: Nucleic acid molecules comprising a nucleotide sequence encoding an activating chimeric antigen receptor (aCARs) are provided, said aCARs comprising (i) an extracellular binding-domain specifically binding an antigen selected from an antigen of the commensal gut microflora and a self-cell surface antigen specific to the lamina propria (LP) or submucosa of the gastrointestinal tract; (ii) a transmembrane domain; (iii) an intracellular domain including at least one signal transduction element that activates and/or co-stimulates a T cell; and optionally (iv) a stalk region linking the extracellular domain and the transmembrane domain.

Abstract: A nucleic acid molecule comprising a nucleotide sequence encoding a homodimeric IL-10 linked to a transmembrane-intracellular stretch, optionally through a flexible hinge, is provided as well as a mammalian regulatory T cell (Treg) comprising and expressing the nucleic acid molecule and uses thereof.

Abstract: The present invention provides a method of identifying a target for preparing an inhibitory chimeric antigen receptor (iCAR) or a protective chimeric antigen receptor (pCAR) capable of preventing or attenuating undesired activation of an effector immune cell. Also provided are a list of iCAR targets, as well as vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (i CAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the i CAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: A nucleic acid molecule comprising a nucleotide sequence encoding a homodimeric IL-10 linked to a transmembrane-intracellular stretch, optionally through a flexible hinge, is provided as well as a mammalian regulatory T cell (Treg) comprising and expressing the nucleic acid molecule and uses thereof.

Abstract: The present invention provides a method for identifying a target pair comprising i) an inhibitory chimeric antigen receptor (iCAR) or a protective chimeric antigen receptor (pCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR or pCAR target is directed to a target extracellular polymorphic epitope, and ii) an activating chimeric antigen receptor (aCAR), wherein the aCAR is directed to a target non-polymorphic cell surface epitope of a protein, as well as methods of making and use of such pairs in the treatment of cancer.

Abstract: The present invention provides a method of identifying a target for preparing an inhibitory chimeric antigen receptor (iCAR) or a protective chimeric antigen receptor (pCAR) capable of preventing or attenuating undesired activation of an effector immune cell. Also provided are a list of iCAR targets, as well as vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (i CAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the i CAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Abstract: Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.

Abstract: Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.

Abstract: Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.

Abstract: The invention provides a polynucleotide comprising a sequence encoding a polypeptide that is capable of high level presentation of antigenic peptides on antigen-presenting cells, wherein the polypeptide comprises a ?2-microglobulin molecule that is linked through its carboxyl terminal to a bridge peptide which spans the whole distance to the cell membrane, said bridge peptide being linked to a polypeptide stretch consisting of the full or partial transmembrane and/or cytoplasmic domains selected from the group consisting of a toll-like receptor (TLR) polypeptide, a CD40 polypeptide, and TLR and CD40 polypeptides fused in tandem, that allows the anchorage of the ?2-microglobulin molecule to the cell membrane, and through its amino terminal to at least one antigenic peptide comprising an MHC class I epitope, wherein said antigenic peptide is preferably derived from a tumor-associated antigen or from a pathogenic antigen.

Abstract: The invention provides DNA molecules encoding a chimeric polypeptide comprising (a) a component of a MHC molecule capable of association on a cell surface with an endogenous MHC molecule component of the same class, and (b) an intracellular region of a signal transduction element capable of activating T cells. Component (a) may be a monomorphic component and is preferably beta 2-microglobulin, or a polymorphic class I or class II component. The signal transduction element (b) capable of activating T cells may be a component of T-cell receptor CD3, preferably the CD3 zeta (zeta) polypeptide, a B cell receptor polypeptide or an Fc receptor polypeptide. Immune cells such as a CTLs expressing said chimeric MHC molecules specifically eliminate or inactivate harmful T cells and are useful for treating graft rejection and autoimmune diseases.