The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. In certain embodiments, the compositions and methods described herein lead to the mobilization of a population of CD34.sup.dim cells that have immunosuppressive effects and that can reduce the incidence of graft vs. host disease.

A ProteAse Released chemoKines protein (PARK) comprises a prochemokine moiety comprising a propeptide moiety fused to a chemokine moiety, wherein the chemokine moiety comprises a N-terminus and a C-terminus; and a targeting moiety linked to the prochemokine moiety, wherein the targeting moiety has a binding specificity to a tumor, fibrosis or Alzheimer's Disease associated antigen or receptor.

Embodiments of the disclosure encompass methods and compositions for bone repair and bone injury healing. In some embodiments, the bone repair and bone injury healing utilizes the enhancement of migration of certain types of bone cells upon stimulation by a particular cytokine. In specific embodiments, migration of periosteal skeletal stem cells upon delivery of CCL5 and/or TNFα is enhanced and fosters bone repair and healing.

The present invention relates to the field of structural biology. More specifically, the present invention relates to novel fusion proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use in structure-based drug design and screening. Even more specifically, the invention relates to a functional fusion protein of a cytokine and a scaffold protein wherein the scaffold is a folded protein that interrupts the topology of the cytokine to form a rigid fusion protein that retains its receptor binding and activation capacity. More specifically, chemokine- and interleukin-based functional fusion proteins, and their production and uses, are disclosed herein.

Provided herein are modified NK-92 cells comprising a nucleic acid encoding C—C chemokine receptor type 7 (CCR7) operably linked to a promoter. Optionally, the cells further comprise a nucleic acid encoding C—C motif ligand 21 (CCL21), a nucleic acid encoding C—C motif ligand 19 (CCL19) or a combination thereof. Also provided are compositions and kits comprising the modified NK-92 cells. Provided are methods of making the modified cells and methods of treating cancer using the cells.

The present invention provides immune cells (such as CAR-T cells) having higher antitumor activity than immune cells (such as CAR-T cells) expressing a CAR alone (not expressing cytokines and/or chemokines). A T cell provided in one aspect of the present invention expresses (1) a chimeric antigen receptor (CAR), (2) at least one selected from the group consisting of interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21), and interleukin-27 (IL-27), and (3) CC chemokine ligand 19 (CCL19).

The present invention relates to methods and pharmaceutical compositions for the treatment of tissue lesions. The inventors showed that CCR2 is expressed on FMCs, especially on a subpopulation of progenitor cells, that they call “fetal myeloid progenitor cells” (FMPCs), and mediates the recruitment of these cells to maternal wound tissue. Moreover, the inventors reported that recruited FMCs/FMPCs improve maternal skin wound healing by organizing blood vessel endothelium and secreting pro-angiogenesis peptides, particularly chemokine CXCL1, to enhance angiogenesis in wound. In particular, the present invention relates to CCR2 agonists for use in the treatment of tissue lesions in a subject in need thereof.

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

Provided herein are novel p62 compositions for the modulation of expression of a proinflammatory cytokines, osteogenic transcription factors, a bone resorptive factors and endogenous p62. Consequently, such p62 compositions are useful for prophylaxis and treatment of inflammatory diseases and related methods. In certain embodiments the inflammatory diseases are not cancer-related. In various embodiments, the inflammatory diseases include, but are not limited to osteoporosis, obesity, metabolic syndrome, type 2 diabetes, fat liver, inflammatory bowel disease, chronic pancreatitis, asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), osteoarthritis, multiple sclerosis (MS), psoriasis, congestive heart failure (CHF), atherosclerosis, neurodegenerative diseases (ALS, Parkinson, Alzheimer's, Huntington disease), depression, schizophrenia, gout, asbestosis and silicosis.

Provided are a fusion protein having a CCL3 variant with improved in vivo persistency, protein stability and pharmacological activity and a use thereof, more particularly, a fusion protein comprising a CCL3 variant and an immunoglobulin Fc region and a use thereof as a therapeutic agent for lymphopenia, cancer or infection, in which an N-terminal amino acid of a wild-type CCL3α or CCL3β is deleted and an amino acid at a specific position is substituted with a different amino acid at the same position of the wild-type CCL3α or CCL3β in the CCL3 variant.