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.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors (CAR) and/or genetically modified to reduce potential side effects of cellular immunotherapy. Several embodiments relate to genetic modifications to the immune cells, such as Natural Killer (NK) cells, to reduce, substantially, reduce, or eliminate expression of a combination of genes and their corresponding proteins. In several embodiments, one edit is to reduce expression of a marker by the immune cells that would otherwise cause them to be self-targeted by the CAR and at least two additional gene edits to enhance the cytotoxicity and/or persistence of the resulting cells. In several embodiments, the CAR targets CD70, and in some embodiments is used for renal cell carcinoma immunotherapy.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.

Described herein are chimeric receptors comprising G-CSFR extracellular domains and the intracellular domains of various multi-subunit cytokine receptors for selective activation of cytokine signaling in cells of interest. In certain aspects, the selective activation of cytokine signaling in cells expressing the chimeric receptors described herein includes the ability to specifically stimulate adoptively transferred cells.

Described herein are methods and compositions for selective activation of cells using variant cytokine receptor and cytokine pairs, wherein the cytokine receptors comprise an extracellular domain (ECD) of granulocyte-colony stimulating factor receptor (G-CSFR). In certain embodiments, the methods and compositions described herein are useful for exclusive activation of cells for adoptive cell transfer therapy. Thus, included herein are methods of producing cells expressing variant receptors that are selectively activated by a cytokine that does not bind its native receptor. Also disclosed herein are methods of treating a subject in need thereof, comprising administering to the subject cells expressing an variant receptor comprising an extracellular domain of G-CSFR and co-administering a variant cytokine that activates the variant receptor.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

An immune effector cell expressing a chimeric cytokine receptor comprising a first extracellular antigen binding domain, a first transmembrane domain, and a cytokine receptor intracellular domain; and a functional exogenous receptor comprising a second extracellular antigen binding domain, a second transmembrane domain, and an intracellular signaling domain.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

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.