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.

Provided are a bispecific molecule and preparation and use thereof. The bispecific molecule includes a molecule that specifically binds an interleukin-1 receptor (IL-1R) and an antibody that targets a free inflammatory factor. The molecule that specifically binds the cell surface interleukin-1 receptor (IL-1R) aggregates the antibody that targets the free inflammatory factor linked thereto on or near the cell surface, thereby the local concentration of the bispecific molecule on or near the cell surface is increased, adverse reactions are avoided, treatment effectiveness is increased and the infection risk of patients is also reduced.

The present invention relates, in part, to targeted chimeric proteins with beneficial therapeutic effects, including, for example, effects mediated by chimeric proteins which comprise modified signaling agents two or more targeting moieties. Methods of treatment and pharmaceutical compositions comprising the chimeric proteins are also provided. The present invention finds use in the treatment of various disease and disorders.

Methods of treating a subject in need thereof are provided which include: administering a recombinant platelet derived growth factor D (PDGF D) composition to a mesenchymal stem cell of the subject and/or a progenitor derived therefrom, in vivo, or ex vivo, producing a treated mesenchymal stem cell of the subject and/or a progenitor derived therefrom, thereby stimulating the mesenchymal stem cell (MSC) and/or a progenitor derived therefrom. Cells expressing a recombinant PDGF D composition of the present are administered to the subject for in vivo delivery of the recombinant PDGF D composition according to aspects of the present disclosure. Methods and compositions are provided including recombinant PDGF D hemidimer (HD) including a full-length PDGF D polypeptide and a C-terminal growth factor domain of PDGF D, which lacks a CUB domain, promoting regulation of bone marrow MSC differentiation into osteogenic lineage cells.

The present invention provides compounds, compositions, and methods for detecting, diagnosing and treating cancers such as glioblastoma multiforme.

A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13Rα2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

Disclosed herein are extracellular vesicles such as exosomes that selectively target cells such as skeletal muscle cells. Such vesicles include skeletal muscle targeting moieties and can be used to selectively deliver a payload to skeletal muscle cells or tissue.

An EL-15 super agonist (IL-15N72D:IL-15RαSU/IgG1Fc; N-803) increases circulating NK cells, effector memory and effector memory RA cells in post-allogeneic hematopoietic stem cell transplant patients (HCT). Methods of treatment include administration of N-803 to subjects in need of such treatment.

The invention relates to novel Evasin polypeptides with novel chemokine-binding properties and their use in inhibiting chemokines or detecting chemokine expression and inflammation.

The present invention relates to a kit-of-parts comprising and a composition comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate comprising a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of binding to a cancer antigen; and at least one antibody, wherein said at least one antibody is capable of modulating an immune checkpoint protein. Further the invention relates to this composition or kit-of-parts for use in the treatment of cancer.