The present invention provides programmable universal cell receptors (PUCRs) comprising a catalytic antibody region, a transmembrane domain and a cytoplasmic domain. The PUCRs disclosed herein may be conjugated to a specificity agent in order to program the receptor for specificity to any molecule of interest. Also provided are nucleic acids encoding such PUCRs, and cells expressing the PUCRs. Such cells may be used in treating a variety of medical conditions and diseases including cancer and infectious diseases.

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompansses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.

The application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described.

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Methods and compositions involving miR-122, miR-15b, miR-21, and miR-155, which are useful for the treatment of various diseases, such as cancers, are described. Further described are methods and compositions useful for increasing, activating, or regulating NK cells and surface antigens.

The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.

Provided are compositions and methods relating to regulatable chimeric antigen receptors (RCARs), natural killer cell receptor CARs (NKR-CARs), and regulatable NKR-CARs (RNKR-CARs), where the intracellular signaling or proliferation of the RCAR or RNKR-CAR can be controlled to optimize the use of an RCAR/NKR-CAR- or RNKR-CAR-expressing cell to provide an immune response. Cells can be engineered to express a RNKR-CAR or to express a RCAR and a NKR-CAR (e.g., inhibitory NKR-CAR). For example, a RCAR or RNKR-CAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR or RNKR-CAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Methods and compositions for treating or ameliorating lower back pain by administering an effective amount of one or more cell types, alone, and/or in combination with a matrix, and/or in combination with growth factors, in order to stimulate lumbar angiogenesis, decrease inflammation, and stimulating regeneration.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

The invention relates to the field of cell therapy, particularly NK cell mediated therapy. The present invention relates to a method of producing an ex vivo population of cells, preferably NK cells, from at least two umbilical cord blood units (UCB units), or fraction thereof containing said cells, by pooling said at least two UCB units to produce said population of cells. The present invention relates to the use of said cells, preferably NK cells, obtainable or obtained by the process according to the invention, as a composition for therapeutic use, preferably for the treatment of cancer and chronic infectious disease.