A method of creating antigen-specific, chimeric antigen receptor (CAR) T cells capable of secreting regenerative growth factors upon activation of said CAR. In one embodiment said regenerative CAR-T cells possess a CAR capable of selectively recognizing damaged tissue. In one embodiment said CAR recognizes damage-associated molecular patterns (DAMPs) such as ATP, HMGB-1, matricryptins, cold-inducible RNA-binding protein, histones and mitochondrial DNA. Upon activation of said CAR said regenerative CAR-T cell is induced to produce one or more regenerative growth factors. In some embodiments the invention provides a suicide gene in said regenerative CAR-T cells in order to remove said cells after their therapeutic purpose is completed.

The peptide of the present invention performs a function, which is the same as or similar to that of natural interleukin (IL)-3, and has superior skin permeability due to the small size thereof. In addition, the peptide of the present invention suppresses the activation of NF-κB and nuclear transition by inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK signaling pathway, and suppresses the expression of a RANKL or an inflammatory cytokine-induced tartrate-resistant acid phosphatase (TRAP), cathepsin K, or TNF receptor type 1 or type 2, thereby inhibiting osteoclast differentiation depending on the treatment concentration. Moreover, the peptide of the present invention can contribute to osteoblast differentiation by promoting the expression of osteoblast differentiation markers such as osteocalcin (OCN), osteoprotegerin (OPG), bone sialoprotein (BSP), or osteopontin (OPN). Therefore, the superior activity and stability of the peptide of the present invention are useful for medicines, sanitary aids, or cosmetics.

The present invention relates to recombinant optimized polynucleotide encoding a cytokine or cytokine receptor and to methods of making a recombinant optimized polynucleotide encoding a cytokine or cytokine receptor.

Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and/or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

An object of the present invention is to provide a humanized mouse in which human hematopoietic stem cells can be engrafted for a long term. The present invention relates to a humanized rodent having human neutrophils circulating in a periphery, obtained by transplanting a human hematopoietic stem cell into a human G-CSF gene knock-in rodent, which is an immunodeficient rodent deficient in a G-CSF receptor function by knock-in of a human G-CSF gene at a G-CSF receptor locus, wherein a human G-CSF is expressed and a rodent G-CSF receptor is not expressed.

The present disclosure provides an immunodeficient NOD.Cg-Prkdc.sup.scidIl2rg.sup.tm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and a HLA-A2/H2-D/B2M transgene encoding (i) a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha 1, and alpha2 binding domains of a human HLA-A2.1 gene and (ii) alpha3 cytoplasmic and transmembrane domains of murine H2-db.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.