The present disclosure provides transgenic T cells expressing engineered dimeric antigen receptors (DARs) that bind GD2. where the DAR includes a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. The transgenic T cells can be used for directed cell therapy.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The present invention relates to a combination comprising at least fusion protein comprising a binding protein specifically recognizing a cancer-related antigen and an inflammatory cytokine, and a chimeric antigen receptor (CAR)-T cell recognizing a cancer-related antigen.

The disclosure provides a method of preconditioning a subject for chimeric antigen receptor (CAR) T cell therapy. The method comprises administering to the subject a composition comprising a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, at least one day prior to administering CAR T cell therapy to the subject. The disclosure also provides a method of treating a solid tumor in a subject, the method comprising administering to a subject comprising a surface antigen negative solid tumor a first composition comprising the nanoparticle, wherein the nucleic acid within the nanoparticle encodes the surface antigen, and a second composition comprising a CAR T cell that targets the surface antigen.

The disclosure provides a method of preconditioning a subject for chimeric antigen receptor (CAR) T cell therapy. The method comprises administering to the subject a composition comprising a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, at least one day prior to administering CAR T cell therapy to the subject. The disclosure also provides a method of treating a solid tumor in a subject, the method comprising administering to a subject comprising a surface antigen negative solid tumor a first composition comprising the nanoparticle, wherein the nucleic acid within the nanoparticle encodes the surface antigen, and a second composition comprising a CAR T cell that targets the surface antigen.

Provided are NK-92 cells expressing a chimeric antigen receptor (CAR). The CAR can comprise an intracellular domain of Fc?RI?. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer or a viral infection, comprising administering to the patient NK-92-CAR cells.

Provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising engineered immune cells that overexpress miR200c and/or EpCAM.

The present invention relates to engineered extra-cellular vesicle internalizing receptors that have the ability to enhance uptake, processing, and presentation to T-cells of tumor-associated antigens by an antigen-presenting cell. It further relates to vectors or antigen presenting cells expressing said receptors, composition and uses thereof for the prevention and/or treatment of a cancer.

The present invention regards methods and/or compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes IL-2, IL-4, IL-7, and/or IL-15 and additionally or alternatively comprise a chimeric antigen receptor (CAR). In specific embodiments, the CAR is a CAR that targets the GD2 antigen, for example in neuroblastoma

Provided is a method of activating a recombinant immune cell expressing a synthetic receptor comprising an intracellular domain derived from killer cell immunoglobulin-like receptor 4 (KIR2DL4). Synthetic receptors described herein allow for the activation of recombinant immune cells against an antigen of interest without the deleterious effects of immune cell hyperactivation by existing CARs. The recombinant immune cells can thus be used to in the treatment of cancers or infectious diseases in subjects in need thereof, while limiting the hyperactivation of an immune response associated with traditional recombinant cell-based therapies.