308results about "Transforming growth factor" patented technology

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a dual mutant transforming growth factor beta 1 (dmTGFB1) under control of a promoter sequence and a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TGFBR2. In certain embodiments, the cells further comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA; a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG; and insertion of sequence(s) encoding a regulatory T cell promoting molecule, and compositions and uses thereof.

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.

To identify lipid metabolites that control Th17 cell differentiation and lipid biosynthetic enzymes involved therein, and based on that, to provide a screening method for a therapeutic agent for diseases caused by excessive Th17 cell responses.SOLUTION: Provided is 1-oleoyl-lysophosphatidylethanolamine (LPE(1-18:1)) as a lipid metabolic product that controls Th17 cell differentiation. Since LPE(1-18:1) binds to RORγt with high specificity and promotes differentiation into Th17 cells, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained by selecting a compound that inhibits the binding of LPE(1-18:1) to RORγt. Also provided are five lipid metabolic enzymes (Gpam, Gpat3, Lplat1, Pla2g12a, and Scd2) that are responsible for the biosynthesis of LPE(1-18:1) and control Th17 cell differentiation. By selecting a compound that inhibits the activity or expression of these lipid metabolic enzymes, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained.SELECTED DRAWING: None

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a dual mutant transforming growth factor beta 1 (dmTGFB1) under control of a promoter sequence and a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TGFBR2. In certain embodiments, the cells further comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA; a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG; and insertion of sequence(s) encoding a regulatory T cell promoting molecule, and compositions and uses thereof.

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.

To provide induced regulatory T cells with high function and stable immunosuppressive function.SOLUTION: The present invention provides an induced human regulatory T cell having at least one characteristic selected from the group consisting of FoxP3-positive, CTLA4-positive, NT5E-positive, ITGAE (CD103)-positive, AREG-positive, CD172 g-positive, and CD26-positive, which is induced by obtaining stable inducible T cells induced from human peripheral T cells by stimulation with an anti-CD3 antibody when regulatory T cells are induced from human peripheral T cells, subsequently subjecting the cells to resting culture, stimulating the cells with anti-CD3 antibody again to culture them, and further subjecting the cells to resting culture.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.

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.

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 application relates to the field of oncology, cancer immunotherapy, molecular biology and recombinant nucleic acid technology. In particular, the invention relates to genetically-modified eukaryotic cells comprising modulated TGF Beta signaling. The application further relates to the use of such genetically-modified eukaryotic cells for treating a disease, including cancer, in a subject.

The invention features methods of treating a transfusion dependent subject having myelofibrosis, a cytopenia associated with myelofibrosis, such as anemia, thrombocytopenia, or neutropenia, or receiving treatment with a cytopenia-associated myelofibrosis treatment by administering to the subject an activin receptor type II (ActRII) signaling inhibitor, optionally in combination with a cytopenia- associated myelofibrosis treatment. The ActRII signaling inhibitor may be an antibody that binds to an ActRII ligand, an ActRII antibody, or an ActRII ligand trap.

The present disclosure provides a polypeptide complex comprising a target binding polypeptide that binds to a molecule on a target cell or a molecule in an extracellular matrix (ECM); and small latent complexes comprising in particular a dimer latent related polypeptide (LAP) or a fragment or derivative thereof, and a dimer mature transforming growth factor beta (TGF beta) family polypeptide or a fragment or derivative thereof. Polypeptides (e.g., fusion polypeptides), and related polynucleotides, vectors, cells, and pharmaceutical compositions are also provided. Also provided are methods of treating subjects using, for example, these polypeptide complexes and / or these fusion polypeptides or pharmaceutical compositions thereof.

The invention discloses a brain glioma animal model construction method based on an AAV mediated immune microenvironment. The method comprises the following steps: selecting an immunodeficient mouse at the right age; human CD34 + hematopoietic stem cells are injected for immune system reconstruction; human CD45 + immune cells in the peripheral blood PBMC are detected; the method comprises the following steps: selecting tumor tissues with high-expression brain glioma marker genes, carrying out rapid qPCR (quantitative polymerase chain reaction) or targeted RNA-seq immunohistochemical multiple verification, and screening consistent tumor tissues; the method comprises the following steps: physically dicing tumor tissues, treating the tumor tissues with pretreatment liquid, digesting the tumor tissues into single-cell suspension, and inoculating the single-cell suspension into a mouse cranium; an AAV vector carrying a specific immune regulation gene is injected into the tail vein of the mouse, and the brain glioma immune microenvironment is regulated; when it is observed that the tumor tissue grows stably and has immune cell infiltration characteristics, construction of the brain glioma animal model is completed. Compared with an existing model, the brain glioma model which is more stable, more scientific and closer to the human immune background is provided, and the brain glioma model is suitable for related immunotherapy drug screening and mechanism research.

Provided are multispecific binding agents comprising anti-fibroblast activation protein (FAP) antibodies and one or more monovalent ligand traps. The multispecific binding agents may be used in therapeutic methods for treating FAP associated diseases or disorders.

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.

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.

Disclosed are methods of treating an eye disease by administering a recombinant adeno-associated virus (AAV) vector that encodes the proteoglycan decorin to the eye of a subject. Also provided are animal models of glaucoma that are generated using a recombinant AAV vector that encodes a constitutively active variant of transforming growth factor beta 2 (TGFβ2CS).

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.

In part, the present disclosure relates methods for treating heterotopic ossification or one or more complications of heterotopic ossification. In particular, the disclosure provided methods for treating heterotopic ossification by administering to a patient in need thereof one or more TGFβ antagonists, optionally in combination with one or more additional active agents or supportive therapies for treating heterotopic ossification. For example, in some embodiments, the disclosure provided methods for treating heterotopic ossifications by administering to a patient in need thereof an effective amount of a TβRII polypeptide.

Provided herein are codon-optimized Smad7 polynucleotides and vectors comprising codon-optimized Smad7 polynucleotides for use in increasing or prolonging Smad7 expression in a subject.

The present disclosure provides for a synthetic immunogenic protein for use as an immuno-modulatory agent to enhance mammalian immune reactions towards conjugated protein or peptide containing antigens that are otherwise poorly immunogenic, including but not limited to self-antigens. The chimeric immunogenic proteins of the present disclosure can be used in the treatment of many illnesses, including but not limited to cancers, infectious disease, autoimmune disease, allergies and any clinical indication involving or affected by the immune response of a mammalian host.

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 present disclosure relates to T cells capable of co-expressing a T cell receptor ("TCR") with a dominant negative TGFβ receptor ("dnTGFβR") polypeptide and / or a CD8 polypeptide, and their use in adoptive cell therapy. The present disclosure further provides dnTGFβR polypeptides, vectors thereof, and related methods. The present disclosure also provides modified CD8 polypeptides, vectors thereof, and related methods of making and using.

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.

The present invention relates to a pretreatment method for separating and purifying TGF-β3 protein from Escherichia coli with high efficiency and high purity, and a method for purifying TGF-β3 protein including the same. When using the pretreatment method of the present invention and the purification method including the same, since E. coli is used, the process is simpler and higher productivity is expected compared to animal cell culture methods, and therefore highly pure TGF-β3 protein can be separated and purified from E. coli with high efficiency.

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.

A fusion protein containing an anti-TIGIT antibody and TGF-βR, and a pharmaceutical composition and the use thereof. Specifically, disclosed is a fusion protein containing a first protein functional region for targeting TIGIT, and a second protein functional region having a TGF-β binding activity, wherein the first protein functional region is an anti-TIGIT antibody or an antigen-binding fragment thereof, and the heavy chain variable region of the anti-TIGIT antibody contains HCDR1-HCDR3 with amino acid sequences as respectively shown in SEQ ID NOs: 3-5, and the light chain variable region thereof contains LCDR1-LCDR3 with amino acid sequences as respectively shown in SEQ ID NOs: 8-10. The fusion protein can simultaneously inhibit TIGIT and reduce the TGF-β level, and has good potential for preparing an anti-tumor drug.