Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. As a preferred example, the present disclosure relates to fusion polypeptides comprising (a) a first polypeptide comprising a first secretion signal, a first multimerization domain, a first transmembrane domain, and an actuator domain, (b) a viral self-cleaving polypeptide, and (c) a second polypeptide comprising a second secretion signal, a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand, a second multimerization domain, and a second transmembrane domain.

The present invention relates, inter alia, to compositions and methods, including chimeric proteins comprising an extracellular domain of a Type I transmembrane protein or a portion of a membrane-anchored extracellular protein and a portion of the extracellular domain of a Type II transmembrane protein, wherein the Type II transmembrane protein is naturally expressed on the surface of a Natural Killer (NK) cell that find use in the treatment of disease, such as cancer and viral infections.

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that arc engineered to express a CTX-CAR described herein.

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).

Disclosed herein are antibodies and compositions used for binding to Gal3. Some embodiments allow for disrupting interactions between Galectin-3 (Gal3) and cell surface markers and/or proteins associated with neurological diseases and/or proteopathies, such as Alzheimer's disease. Additionally, disclosed herein are methods of treatment and uses of the antibodies or binding fragments thereof for the treatment of fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, pulmonary fibrosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, sepsis, atopic dermatitis, psoriasis, cancer, brain cancer, breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, bladder cancer, stomach cancer, hematological malignancy, neurological diseases and/or proteopathies. Furthermore, some embodiments provided herein can cross the blood-brain barrier and can be conjugated or otherwise associated with one or more payloads for the treatment of a neurological disease.

Provided are NKG2D fusion proteins and their uses for the treatment of various diseases.

Implantable scaffolds that treat solid tumors and escape variants and that provide effective vaccinations against cancer recurrence are described. The scaffolds include genetically-reprogrammed lymphocytes and a lymphocyte-activating moiety.