The present invention relates to a novel IL-10 variant protein and use thereof, and more particularly, to a novel IL-10 variant protein whose immune stimulatory activity is inhibited and yield of production is increased by forming monomers when expressed.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

Mesenchymal stromal cells are engineered to express a chimeric antigen receptor (CAR), that specifically binds a marker of activated myeloid cells, including without limitation folate receptor beta; and are administered to an individual for treatment of inflammation at sites characterized by the presence of activated myeloid cells.

De novo designed polypeptides that bind to IL-2 receptor β.sub.c heterodimer (IL-2Rβ.sub.c), IL-4 receptor α.sub.c heterodimer (IL-4Rα.sub.c), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.

A composition for wound healing, comprising an amount of a macrophage proresolving polarizer, wherein the amount is effective to promote wound healing. The composition includes wherein the macrophage proresolving polarizer is lipin-1. The composition includes wherein the composition includes one, two, or three of IL-4, apoptotic cells (ACs), and AC derived lipids. The composition includes wherein the macrophage proresolving polarizer is a lipin-1 transcriptional coregulatory activity promoter. The composition includes, wherein the lipin-1 transcriptional coregulatory activity promoter is an inhibitor of lipin-1 macrophage pro-inflammatory responses enzymatic activity. A method for promoting wound healing, comprising contacting a wound on a skin of a mammal with the composition. A kit comprising one or more containers including the composition in sterile packaging. A wound healing device comprising a substrate and an amount of an amount of a macrophage proresolving polarizer, wherein the amount is effective to promote wound healing.

An object of the present invention is to improve the efficiency of a method for producing chimeric antigen receptor (CAR)-expressing cells. The present invention provides a method for producing genetically modified mammalian cells, comprising the steps of: a) introducing a polynucleotide encoding a chimeric antigen receptor (CAR) protein to a cell population comprising T cells derived from a mammal by a transposon method to obtain a genetically modified cell population; b) providing an endogenous cell population derived from the mammal expressing a protein that binds to the CAR; and c) coculturing the genetically modified cell population of the step a) and the endogenous cell population of the step b).

Safe, rapid, and efficient methods for producing antigen-specific T cells recognizing human papilloma virus (HPV antigens); HPV-specific T cells, and methods for treating HPV infections and HPV-related malignancies by adoptive transfer of HPV-specific T cells.

There is described herein a method for inducing Tc22 lineage T cells from a population of CD8+ T cells, the method comprising: a) providing a population of CD8+ T cells; b) activating the population of CD8+ T cells; and c) culturing or contacting the population of CD8+ T cells with IL-6.

Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

The present invention relates to interleukin-4 receptor-binding fusion proteins. More specifically, the invention provides, in part, fusion proteins that include an interleukin-4 or interleukin-13 protein moiety joined to an anti-apoptotic Bcl-2 family member protein moiety.