121results about "Transforming growth factor" patented technology

Fusion molecules comprising an obesity-related peptide moiety, fused to a myostatin pathway inhibitor moiety are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods of using, the fusion molecules.

The invention relates to proteins for use in the prevention, treatment or amelioration of kidney diseases or kidney damage, more particularly where the protein is a follistatin-fusion protein.

Oncolytic viruses encoding recombinant TGF-β engineered to prevent homodimerization and recruitment of TGF-β receptor I are described. The engineered TGF-β minimonomer functions as a dominant-negative TGF-β inhibitor. Oncolytic viruses encoding TGF-β minimonomers can be used for cancer immunotherapy to inhibit the immunosuppressive tumor microenvironment. Provided are oncolytic viruses encoding recombinant TGF-β monomers, such as human recombinant TGF-β monomers.

Provided herein are macromolecules that conditionally induce a cellular effector function (e.g., a biological or therapeutic activity) based on the presence of a disease signature ligand, compositions comprising the same, and methods of using the same.

Provided herein are methods for generating a protein product, comprising: providing a plant seed; contacting said plant seed with a protein expression vector that encodes for a protein; transiently expressing said protein in said plant seed using said protein expression vector, and isolating said protein from said plant seed to obtain a protein product.

The invention relates to the technical field of biological medicines, and discloses application of INHBC as a target spot in prevention and / or treatment of metabolic diseases. Specifically, the invention relates to application of substances for promoting INHBC gene expression or improving protein activity in preparation of products for preventing and / or treating metabolic diseases, and the metabolic diseases comprise diseases caused by energy metabolism disorder, such as obesity, diabetes, fatty liver disease, hyperlipidemia and the like. According to the application disclosed by the invention, liver specific overexpression or INHBC knock-in can improve mouse liver fatty degeneration and abnormal glucose metabolism induced by high fat diet, and in addition, the heat production activity of mouse adipose tissues can be enhanced, so that obesity induced by high fat diet is inhibited; the compound has an important application value in preventing and / or treating metabolic diseases such as obesity, type 2 diabetes and fatty liver diseases.

Disclosed herein are a means to prevent and / or ameliorate age, disease and obesity associated metabolic diseases, such as diabetes and impaired glucose tolerance. Also disclosed are compositions and methods that relate to the findings that GDF11 prevents weight gain, improves glucose tolerance and reduces hepatosteatosis in aged mice administered a high fat diet. In particular, the methods and compositions described herein relate to increasing the level of GDF11 in a subject, thereby treating or preventing the development of obesity in the subject, reducing the metabolic consequences of obesity and improving the subject's metabolic health.

Recombinant TGF-β2 monomers engineered to prevent dimerization and block TGF-β signaling are described. The engineered monomers lack the ability to bind and recruit TGF-β type I receptor (TbRI), but retain the capacity to bind the high affinity TGF-β type II receptor (TbRII). The TGF-β2 monomers also include additional modifications that increase their affinity for TbRII, reduce their aggregation and / or improve their folding. Nucleic acid molecules and vectors encoding the recombinant TGF-β2 monomers are also described. Isolated cells, such as T cells, can be re-programmed with a TGF-β2 monomer-encoding nucleic acid or vector to secrete the monomer. Use of the recombinant TGF-β2 monomers and / or cells producing the recombinant TGF-β2 monomers, to inhibit TGF-β signaling, such as to treat disorders associated with aberrant TGF-β signaling, are also described.

The present invention relates to novel naturally occurring and synthetic active peptides or peptide-derived agents designed for the cosmetic treatment of human skin, as well as cosmetic formulations and compositions containing them. The active agents are effective in restoring, promoting, and maintaining healthy skin. In particular, the present invention discloses a combination or set of skin active agents, including stem cell factors, that modulate the skin microenvironment and regulate skin stem cell behavior, thereby effectively healing, regenerating, and improving the condition of aged or damaged skin.

The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and / or or neurodegeneration.

The invention provides a regulatory T cell with improved phenotype and functional stability and a preparation method and application thereof. The regulatory T cell disclosed by the invention is co-expressed by membrane protein GARP and TGF-beta, and specifically, the TGF-beta comprises a C33S point mutation precursor TGF-beta 1; further, the regulatory T cell co-expresses a cytokine and a sorting marker, specifically, the cytokine comprises IL-10, and the sorting marker comprises a truncated nerve growth factor receptor tNGFR. The regulatory T cell has more stable phenotype and function stability in in-vivo and in-vitro environments, has important enlightenment value for improving the function stability problem of the regulatory T cell in an inflammatory environment, and has wide application prospects in the fields of treatment of autoimmune diseases, intervention of organ transplantation rejection and the like.

The present invention relates to a composition for treating or preventing neurodevelopmental disorders, particularly autism spectrum disorder, by selectively activating brain-resident regulatory T cells (Tregs). The present composition comprises IL-2 or an IL-2 gene (AAV-GFAP-IL-2) as an active ingredient, and induces Treg proliferation in the brain to alleviate neuroinflammation and improve behavioral defects.

This invention provides a TGFβRII-ECD-based trap with tuned isoform specificity. [Solution] A tetravalent TGFβ receptor-extracellular domain-based trap having a tuned isoform specificity profile for neutralizing TGFβ ligands, and methods for using the same in the treatment of diseases and conditions related to TGFβ, particularly TGFβ1 and TGFβ3, are provided. In particular, a TGFβ conjugate is provided that is designed to tune TGFβ isoform specificity in order to maximize therapeutic effect in specific disease indications while minimizing adverse effects. The TGFβ conjugate comprises two polypeptides assembled via a multimerizing domain, each polypeptide having two TGFβII receptor (TGFβR) ligand-binding domains linked as a doublet, where the linker is selected to tune isoform specificity.

In one aspect, the invention relates to synthetic molecules, compositions and pharmaceutical compositions, which are useful for delivering a bioactive moiety to a site of injury. Also disclosed are methods of treating a tendon injury, methods of treating a fracture, methods of treating a bone stress injury, methods of enhancing incorporation of allograft tissues, methods of promoting repair or regeneration of enthesis tissue during or after an orthopedic surgical procedure, and method of treating osteoporosis, osteoarthritis and / or cartilage defects using the disclosed molecules, compositions and pharmaceutical compositions.

This invention relates to a method for producing extracellular matrix using connective tissue cell culture and to the uses of the produced extracellular matrix. More specifically, it relates to a method for culturing connective tissue cells using a serum-free and heterogeneous culture medium, which can be effectively used to increase the amount of extracellular matrix produced. Furthermore, the extracellular matrix produced by the production method of this invention is derived from human cells and does not contain any heterogeneous components such as fetal bovine serum, making it safe and useful for future development of cell therapy agents, medical supplies, medical devices for tissue treatment, or cosmetic raw materials.

This disclosure provides transforming growth factor β (TGF-β) peptide constructs and complexes that can be used for the therapeutic treatment of diseases, including autoimmune diseases. Nucleic acids encoding the constructs and complexes, as well as methods for preparing the constructs and complexes in a cell-based expression system, are also described.

In a method of treating an inflammatory disease induced by a hyperimmune response, a composition is administered to a subject. The composition includes at least one of a chondrocyte and a cell capable of differentiating into a chondrocyte, and a cell into which a gene encoding TGF-β1 is introduced and derived from human embryonic kidney 293 (HEK-293) cell. The composition may be used for treating an inflammatory disease induced by a hyperimmune response.

Provided herein are macromolecules that conditionally induce a cellular effector function (e.g., a biological or therapeutic activity) based on the presence of a disease signature ligand, compositions comprising the same, and methods of using the same.

One embodiment of the present invention relates to a fusion protein or a dimer thereof comprising a polypeptide represented by formula (I) and a polypeptide represented by formula (II). The fusion protein or a dimer thereof according to the present invention is a material with improved in vivo durability, protein productivity, and stability, and has excellent effects on weight loss and blood glucose regulation.

Provided herein are compositions and methods for treating musculoskeletal fibrosis and / or scarring by ablating intracellular signaling through specific cell surface receptors through genetic editing. In some aspects, the compositions and methods are directed to the TGFB1 ligand. In other aspects, the compositions and methods are directed to the TGFB1 receptors (TGFBR1 / TGFBR2). In some aspects, the compositions and method are to treat or prevent post-trauma fibrosis and / or scarring. In some aspects, the compositions and method are to treat or prevent postoperative fibrosis and / or scarring. In some aspects, the compositions and method are for treating or preventing localized nociception, inflammation, degeneration, or morphological changes associated with fibrosis and / or scarring.

An umbilical cord mesenchymal stem cell and application thereof in treating osteoarthritis. The application discloses a dual-response hydrogel drug delivery system for osteoarthritis treatment and application thereof, and relates to a synergistic design of a bifunctional fusion protein BFP, an epigenetic regulator TSA and a temperature-sensitive-enzyme response hydrogel. The bifunctional protein BFP contains a cartilage induction domain CIP-2 and an anti-inflammatory domain AIP-3, which are connected in series through a rigid connection peptide EAKAK, and can specifically activate the TGF-beta pathway and respond to MMP9 to release the anti-inflammatory fragment. The temperature-sensitive-enzyme dual-response hydrogel is composed of thiolated hyaluronic acid and poloxamer 407, and can rapidly gelate within 3.5±0.5 minutes at 37 DEG C, the gel transition point is 29.2±0.3 DEG C, and the synergistic release of BFP / TSA can be realized in the presence of MMP9, and the 72-hour release rate reaches 86.7%. Experiments prove that the system can make the SOX9 / COL2A1 gene expression of UC-MSCs increase by 6.77 times and 5.9 times respectively, the GAG deposition amount reaches 0.81 OD630, the ICRS score in the rat OA model increases by 267%, and the serum MMP-13 level decreases by 78.3%. Therefore, the technology of the application provides a new direction for the precise treatment of osteoarthritis.

Provided herein are engineered receptors that engage cytokine signaling. Also provided herein are engineered receptors for modulating TGF-beta signaling, methods of modulating TGF-beta signaling, and methods of using chimeric antigen receptors to treat cancer.

The present invention relates to methods and compositions comprising a delivery vehicle for delivery of tissue trafficking modulators to modulate the trafficking of immune cell to a specific locus. The invention also relates to methods for treating or preventing a disease and disorder, including cancer, an infectious disease and an immunological disorder.

To provide compositions and methods for modulating TGFβ superfamily signaling.SOLUTION: The disclosure provides TβRII polypeptides and the use of such TβRII polypeptides as selective antagonists for GDF15, TGFβ1 or TGFβ3. As described herein, polypeptides comprising part or all of the TβRII extracellular domain (ECD), with or without additional mutations, bind to and / or inhibit GDF15, TGFβ1 or TGFβ3 with varying affinities. Thus, in certain aspects, the disclosure provides TβRII polypeptides for use in selectively inhibiting TGFβ superfamily associated disorders.SELECTED DRAWING: None

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

This invention relates to improving cancer treatment methods using PD-1 / PD-L1 antibodies. In particular, this invention is based on the finding that patients with a TGFβ-specific T cell response are likely to show favorable outcomes in cancer treatment with PD-1 / PD-L1 antibodies. Therefore, this invention provides treatment for such patient groups with PD-1 / PD-L1 antibodies and actively promotes the TGFβ-specific T cell response in order to enhance the therapeutic effect of PD-1 / PD-L1 antibodies.

The present disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the present invention have reduced or minimal cytokine receptor activating activity despite containing a functional cytokine polypeptide. When activated, for example, by cleavage of a linker connecting a blocking moiety, e.g., a steric blocking polypeptide, to the active cytokine, the cytokine can bind to its receptor and cause signal transduction. Typically, the fusion protein further comprises an in vivo half-life extending element that can be cleaved from the cytokine in the tumor microenvironment.

An object of the present invention is to provide EGFR CAR-T cells expected to be effective for tumors expressing EGFR. The present invention provides a polynucleotide encoding a chimeric antigen receptor (CAR) protein having a target-binding domain that binds to epidermal growth factor receptor (EGFR), a transmembrane domain, and an intracellular signaling domain, wherein the target-binding domain is a ligand for EGFR, and a vector comprising the polypeptide, and a genetically modified cell having the polypeptide or the vector introduced thereinto.

Aspects of the present disclosure relate to the discovery that antagonizing pyruvate carboxylase and glutaminase inhibits cell proliferation and extracellular matrix production. Thus, methods and compositions disclosed herein may be used to treat fibrotic disease and cancer by inhibiting cell proliferation and extracellular matrix production.