The present invention provides inducible chimeric cytokine receptors responsive to a ligand, e.g., a small molecule or protein, uses of such receptors for improving the functional activities of genetically modified immune cells, such as T cells, comprising the inducible chimeric cytokine receptors, and compositions comprising such cells.

Human or humanized tissues and organs suitable for transplant are disclosed herein. Gene editing of a host animal provides a niche for complementation of the missing genetic information by donor stem cells. Editing of a host genome to knock out or disrupt genes responsible for the growth and/or differentiation of a target organ and injecting that animal at an embryo stage with donor stem cells to complement the missing genetic information for the growth and development of the organ. The result is a chimeric animal in which the complemented tissue (human/humanized organ) matches the genotype and phenotype of the donor. Such organs may be made in a single generation and the stem cell may be taken or generated from the patient's own body. As disclosed herein, it is possible to do so by simultaneously editing multiple genes in a cell or embryo creating a niche for the complemented tissue. Multiple genes can be targeted for editing using targeted nucleases and homology directed repair (HDR) templates in vertebrate cells or embryos.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The use of luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to enrich for primitive hematopoietic stem cell (pHSC) populations, to target pHSC for ablation, and/or to expand pHSC populations are described. The methods can be used to prepare therapeutic hematopoietic stem cell (HSC) populations, to prepare patients for therapeutic HSC transplants, and/or to treat malignancies, such as those associated with hyperproliferative HSC.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Materials and methods of treating a patient with type 2 diabetes mellitus, metabolic syndrome, obesity, infertility, high blood pressure, hyperthyroidism, and hypothyroidism, hyperlipidaemia, osteoporosis, osteoarthritis, hypoadrenalism, polycystic ovary syndrome, or Parkinson's disease comprising administering a therapeutically effective amount of ex vivo cultured activated peripheral blood mononuclear cells (PBMCs) to the patient. The ex vivo cultured activated cells are activated and cultured in a presence of a cytokine and may be autologous or allogeneic relative to the patient.

Materials and methods of treating a patient with type 2 diabetes mellitus, metabolic syndrome, obesity, infertility, high blood pressure, hyperthyroidism, and hypothyroidism, hyperlipidaemia, osteoporosis, osteoarthritis, hypoadrenalism, polycystic ovary syndrome, or Parkinson's disease comprising administering a therapeutically effective amount of ex vivo cultured activated peripheral blood mononuclear cells (PBMCs) to the patient. The ex vivo cultured activated cells are activated and cultured in a presence of a cytokine and may be autologous or allogeneic relative to the patient.