32 results about "Chondroitin Sulfate Proteoglycans" patented technology

The invention relates to the discovery of a novel Chondroitinase Glycoproteins (CHASEGP's), methods of manufacture, and potential uses in conditions where removal of chondroitin sulfates may be of therapeutic benefit. Chondroitinase Glycoproteins require both a substantial portion of the catalytic domain of the CHASEGP polypeptide and asparagine-linked glycosylation for optimal chondroitinase activity. The invention also includes carboxy-terminal deletion variants of CHASEGP that result in secreted variants of the protein to facilitate manufacture of a recombinant CHASEGP. Further described are suitable formulations of a substantially purified recombinant CHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity. CHASEGP is useful for the degradation of glycosaminoglycans and chondroitin sulfate proteoglycans under clinical conditions where their removal is of therapeutic value.

Neural outgrowth in the central nervous system is achieved by administering chondroitinase AC and / or chondroitinase B to degrade chondroitin sulfate proteoglycans that inhibit or contribute to the inhibition of nervous tissue regeneration.

Oligosaccharides, and in particular disaccharides, which are degradation products of chondroitin sulfate proteoglycan are effective for use in treating, inhibiting, or ameliorating the effects of injuries or diseases or disorders that result in or are caused by neuronal degeneration or of disorders resulting in mental and cognitive dysfunction. They are also useful for promoting neurogenesis.

The invention discloses a tissue engineering nerval stent and a preparation method and an application thereof. The chemical extraction method is adopted for removing main antigens, namely cells, axons and myelin sheaths, which can cause the rejection, and chondroitinase ABC is further adopted for removing chondroitin sulfate proteoglycan in xenogeneic nerves, thereby getting acellular xenogenic nerves with a complete vessel of a basilar membrane of an extracellular matrix and can be used as the tissue engineering nerval stent. The tissue engineering nerval stent is applicable to restoring peripheral nerve defect of rats, rabbits, dogs, human beings and the like, plays a very obvious role in promoting the regeneration of the axons and can further increase the length of restoring the peripheral nerve defect, thereby being a great nerve transplantation medical material.

The present invention examined the accumulation of chondroitin sulfate proteoglycans (CSPGs). The present invention relates to neurodegeneration-suppressing agents that are suitable for gene therapy or prevention of neural fibrotic degenerative diseases which induce neural cell death due to an accumulation of abnormal proteins, where the therapies are based on siRNAs against N-acetylgalactosamine-4-O-sulfotransferases (N-acetylgalactosamine-4-O-sulfotransferase-1, N-acetylgalactosamine-4-O-sulfotransferase-2, and N-acetylgalactosamine-4-sulfate 6-O-sulfotransferase (GalNAc4ST-1, GalNAc4ST-2, and GALNAC4S-6ST, respectively)), which are sulfotransferases for acetylgalactosamine, a CSPG side chain, and chondroitinase ABC, an enzyme that degrades chondroitin sulfate, another CSPG side chain.

A method of promoting neural cell regeneration is carried out by contacting a neural cell with a compound that inhibits the binding of a chondroitin sulfate proteoglycan (CSPG) to a cellular (e.g., trans-membrane) PTPσ protein. The neural cell is associated with an injury or neurodegenerative condition.

The present inventors discovered for the first time that intestinal inflammation could be efficiently suppressed by suppressing the production or accumulation of chondroitin sulfate proteoglycans. Specifically, inflammation in the large intestine can be suppressed by using siRNA to suppress the expression of versican, which is one of the chondroitin sulfate proteoglycans. Compounds used as siRNA, such as nucleic acids, can be used as effective agents for suppressing intestinal inflammation. Furthermore, the above finding also suggests that such intestinal inflammation-suppressing agents can be found by screening for compounds that suppress the production or accumulation of chondroitin sulfate proteoglycans.

The present invention relates to hepatic fibrosis-suppressing agents that are suitable for treating or preventing fibrotic liver diseases such as cirrhosis, which comprise as an active ingredient a substance that inhibits the production or accumulation of chondroitin sulfate proteoglycans including chondroitinase ABC and ADAMTS-4; and methods of screening for the agents.The present inventors discovered for the first time that hepatic fibrosis could be efficiently suppressed by suppressing the production or accumulation of chondroitin sulfate proteoglycans. Specifically, fibrosis of liver tissues can be suppressed by administering chondroitinase ABC, a chondroitin sulfate proteoglycan-degrading enzyme, or by using siRNA to suppress the expression of C4ST-1, C6ST-1, or C6ST-2, a sulfotransferase for chondroitin sulfate proteoglycans. Compounds such as nucleic acids that are used as siRNA can be used as effective agents for suppressing hepatic fibrosis. Furthermore, hepatic fibrosis-suppressing agents can be found by screening for compounds that suppress the production or accumulation of chondroitin sulfate proteoglycans.

Compositions and methods are provided for promoting elastin fiber formation (elastogenesis) in a cell, including methods that comprise contacting a cell that is capable of elastogenesis with (i) a mutated biglycan polypeptide that lacks chondroitin sulphate proteoglycan chains, (ii) a versican V3 isoform polypeptide that lacks most or all of the polypeptide regions encoded by one or more of exons 4, 5 or 6 or by exons 9-10 or 11-13, and / or with (iii) metastatin.

This invention provides methods and compositions for reducing chondroitin-sulfate-proteoglycan-mediated inhibition of neuronal growth. The methods and compositions provided herein are particularly useful for treatment of neuronal damage or degeneration.

A composition having tissue repair activity, which is capable of promoting reactions associated with tissue repair, contains at least one selected from the group consisting of a first component that is a protein having a monocyte chemotactic protein-1 (MCP-1) activity, a second component that is a protein having the extracellular domain activity of sialic acid-binding immunoglobulin-type lectin-9 (Siglec-9), and a third component that is at least one of chondroitin sulfate and chondroitin sulfate proteoglycan.

The invention relates to intelligent thermo-sensitive glycosyl hydrogel with a dumbbell structure and a preparation method of the hydrogel. The whole structure of the hydrogel is dumbbell-shaped, small molecular chondroitin sulfate proteoglycans are used as raw materials in preparation, a glycosyl monomer containing polymerizable double bonds is firstly synthesized by means of esterification and etherification reaction, and then double thioester serving as a chain transfer agent is polymerized with an N-alkyl acrylamide thermo-sensitive monomer by a reversible addition fragmentation chain transfer agent free radical polymerization method to prepare the novel intelligent glycosyl hydrogel with the dumbbell structure. The hydrogel has the advantages that the structure can be controlled, the molecular weight of the hydrogel is between that of supramolecular gel and that of polymer gel, the shortcomings of the supramolecular gel and the polymer gel are overcome, carbohydrates are used as raw materials, and the hydrogel serving as a natural biomass resource has fine biocompatibility, biodegradability, non-toxicity, no stimulation and the like that petrochemical raw materials do not have.

The invention relates to a star-shaped polyester compound and a preparation method thereof, which relate to the field of polymer materials. The preparation method is characterized by adopting chondroitin sulfate proteoglycans as a chain transfer center, carrying out ring-opening polymerization reaction on a cyclic ester monomer under the catalysis of an organic metal catalyst, and thus high-efficiently obtaining the polyester compound with a star-shaped topology structure with a high conversion rate. The preparation method is cheap and easy-to-get in raw materials, convenient and practical inoperation, and suitable for large-scale industrial production. The length of a branch chain of the star-shaped polyester compound can be controlled through adjusting a feeding ratio, so that a betterpractical value is achieved. According to the star-shaped polyester compound prepared by adopting the preparation method of the star-shaped polyester compound, the hydrophily is increased, the mechanical property is improved, the molecular weight is controllable, and the star-shaped polyester compound can be used as a raw material of a macromolecule drug carrying microsphere so as to have a greatapplication prospect.

The invention provides a T lymphocyte of a chimeric chondroitin sulfate proteoglycan 4 receptor. The T lymphocyte comprises an extracellular domain structure, a human CD28 transmembrane sequence and an intracellular domain structure, wherein the extracellular domain structure is formed by sequentially connecting a signal peptide sequence, an optimized CSPG4 single-chain antibody sequence and a sequence with a human immunoglobulin G2 mutation sequence as a hinge region in series; a genetic sequence of the optimized CSPG4 single-chain antibody is as shown in any one of SEQ ID NO.33-42; a geneticsequence of the hinge region is as shown in SEQ ID NO.31; and the intracellular domain structure is formed by connecting a human CD28 or 41BB intracellular domain costimulatory domain sequence and ahuman CD3[zeta] intracellular domain sequence in series. The invention also provides a preparation method of the T lymphocyte of the chimeric chondroitin sulfate proteoglycan 4 receptor. Meanwhile, the invention provides an application of the T lymphocyte in preparation of drugs for treatment of head and neck tumors. The optimized CSPG4.CAR-T cell can be used for effectively killing the CSPG4 positive tumor cells in vitro and vivo.

The present invention relates to melanoma-associated chondroitin sulfate proteoglycan (MCSP) epitopes recognized by T cells, especially by CD4+ T lymphocytes (short T-cells) and CD8+ T cells, on human melanoma cells. In more detail, the present invention relates to novel T-cell stimulatory tumour antigenic peptides corresponding to said epitopes (MCSP peptides); to fusion proteins comprising said MCSP peptides; to the use of said MCSP peptides, fusion proteins or of the full length MCSP protein itself or fragments thereof to induce an immune response, especially a T-cell response; to the use of said MCSP peptides, fusion proteins or full length MCSP protein itself or fragments thereof to prepare immune cells, such as mature dendritic cells (DCs) loaded with anyone of the peptides according to the invention, or peptide-specific T-cell clones, especially CD4+ or CD8+ T cell clones; to the use of said MCSP peptides, fusion proteins or MCSP itself or fragments thereof for research and development on / of a cancer treatment; to the use of said MCSP peptides, fusion proteins or MCSP itself or fragments thereof for preparing a medicament for inducing a T cell response in a patient, preferably for the treatment of cancer, more preferably for the treatment of melanoma, including cutaneous and ocular melanoma, and other MCSP expressing tumours such as breast cancer, notably lobular breast carcinoma, astrocytoma, glioma, glioblastoma, neuroblastoma, sarcoma and certain types of leukaemia; to the use of said MCSP peptides, fusion proteins or full length MCSP protein or fragments thereof for the preparation of a medicament, and a diagnostic agent for the treatment and prophylaxis as well the diagnosis of an immune response against tumours; and to the use of said peptide-specific T-cell clones for diagnosing or treating cancer.

A method for modifying access of cells to extravascular spaces and regions comprising administering to a patient an enzyme that cleaves chondroitin sulfate proteoglycans is provided. It has been found that administration of an enzyme that cleaves chondroitin sulfate proteoglycans to a patient disrupts extravasation of cells from the blood stream into tissue. The present invention provides methods of reducing penetration of cells associated with inflammation into tissue of a patient. Several methods are also provided for the regulation and suppression of inflammation comprising administering enzymes that digest chondroitin sulfates. Also provided are methods of treating and preventing inflammation associated with infection, injury and disease.

The use of a cancerous disease modifying antibody (CDMAB) 11 BD-2E11-2 for treating a tumor in humans and methods of isolating and identifying cancerous cells which express a melanoma-associated chondroitin sulfate proteoglycan (MCSP) antigenic moiety. The monoclonal antibody 11 BD-2E11-2 (ATCC accession number PTA-5643), which binds a MCSP antigenic moiety, is cytotoxic to cancer cells which express the antigenic moiety. The monoclonal antibody 11 BD-2E11-2 is useful for delaying the disease progression of a human tumor.

The invention relates to an antibody which binds to chondroitin sulfate proteoglycan 5 (CSPG5) or an antibody fragment thereof, a hybridoma which produces the antibody or the antibody fragment thereof, a nucleic acid comprising a nucleotide sequence encoding the antibody or the antibody fragment thereof, a transformant cell comprising a vector comprising the nucleic acid, a method for producing the antibody or the antibody fragment thereof, a composition comprising the antibody or the antibody fragment thereof, and a method for detecting or measuring an antigen present in the brain, a method for diagnosing or treating a brain disease, a method for enhancing the property of accumulating in a brain of an antibody, and a method for increasing the amount of an antibody in the brain, each of which using the antibody or the antibody fragment thereof, and the like.

A composition having tissue repair activity, which is capable of promoting reactions associated with tissue repair, contains at least one selected from the group consisting of a first component that is a protein having a monocyte chemotactic protein-1 (MCP-1) activity, a second component that is a protein having the extracellular domain activity of sialic acid-binding immunoglobulin-type lectin-9 (Siglec-9), and a third component that is at least one of chondroitin sulfate and chondroitin sulfate proteoglycan.