37 results about "Auto antigen" patented technology

The invention discloses application of ADAM10 or ADAM17 serving as a target spot in preparation of a medicine for preventing / treating membranous nephropathy and application of an ADAM10 or ADAM17 inhibitor in preparation of the medicine for preventing / treating membranous nephropathy. The invention finds that ADAMs mediate the deposition process of immune complexes of autoantigens such as PLA2R1 of membranous nephropathy, and enzyme digestion of podocytes to transmembrane autoantigen proteins such as PLA2R can be inhibited by performing targeted intervention on the activity of ADAMs, especially the activity of ADAM10 and ADAM17, so that immune complexes deposited in glomerulus are reduced, the podocyte damage of membranous nephropathy is improved, and the therapeutic effect is achieved.

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an anti-phospholipase A2 receptor (PLA2R) autoantibody-based B cell receptor (BCR), polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR, and recombinant cells (e.g., T cells) comprising the CAAR, wherein the CAAR comprises a PLA2R autoantigen comprising an extended cysteine rich (eCysR) domain comprising (a) a PLA2R N-terminal peptide and a cysteine rich (CysR) domain, and (b) a C-type lectin domain 7 (CTLD7). The invention also includes methods of making a genetically modified cell, e.g., a genetically modified T cell, expressing a PLA2R-CAAR wherein the expressed CAAR comprises a PLA2R autoantigen comprising an extended cysteine rich (eCysR) domain comprising (a) a PLA2R N-terminal peptide and a cysteine rich (CysR) domain, and (b) a C-type lectin domain 7 (CTLD7).

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as anti-pathogenic T cells to prevent, treat and / or ameliorate autoimmune diseases.

Described herein are methods for treating an autoimmune or inflammatory disease in a patient, comprising administering a composition comprising: a) a plurality of antigen-major histocompatibility class II complexes (antigen-MHCIIs), each antigen-MHCII of the plurality comprising a ubiquitous autoantigen associated with a binding groove of an MHC class II molecule, wherein the ubiquitous autoantigen is chosen from PDC-E2353-367, PDC-E272-86, and PDC-E2422-436 for DRB3*0202; PDC-E2353-367, PDC-E280-94, and PDC-E2535-549 for DRB5*0101; PDC-E2629-648, PDC-E2122-135, and PDC-E2249-263 for DRB4*0101; and PDC-E2249-263 for DRB1*0801; and b) a nanoparticle core possessing a diameter of between 1 and about 100 nanometers; wherein the antigen-MHCs are coupled to the nanoparticle core or a biocompatible layer surrounding the nanoparticle core; and wherein the autoimmune or inflammatory disease is chosen from multiple sclerosis and psoriasis.

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.

The application relates to the technical field of biological medicine, and discloses a drug composition containing nuclear autoantigen sperm protein for promoting myocardial regeneration and repair and application, which comprises an NASP gene; the nucleotide sequence of the NASP gene is shown as SEQ ID NO:1, and the amino acid sequence encoded by the NASP gene is shown as SEQ ID NO:2. The drug composition can promote the number of myocardial cells, repair the necrotic myocardium, and thus improve acute myocardial infarction at the gene level.

A platform for therapy provides a multi-target therapeutic molecule comprising an anti-CD3 antigen binding fragment of an anti-CD3 antibody linked with a linker to two or more auto-antigen(s). The auto-antigens include Dsg1, Dsg3, bullous pemphigoid antigen 180, bullous pemphigoid antigen 230, MuSK, anti-phospholipase A2 Receptor. A pharmaceutical composition comprises a disclosed multi-target therapeutic molecule is disclosed. Methods of treating diseases using the disclosed molecules are disclosed

The present disclosure provides Siglec ligands that have particular linkers. Also provided are conjugates that include a biologically active substance that is covalently bonded to the connecting group of the Siglec ligands. For instance, the biologically active substance can be a biotherapeutic or an autoantigen. The linkers can have advantageous properties that improve the technical qualities of the corresponding conjugates.

The present invention relates to a test kit for performing an assay to detect and measure at least one autoantibody molecule in a subject developing type 1 diabetes (T1D). The invention more specifically relates to a recombinant antigen molecule fused to a bioluminescent reporter protein to detect an autoantibody molecule against a self-antigen. Said self-antigen is preferably expressed by pancreatic islet beta cells and include insulin, proinsulin, Glutamate decarboxylase 65, islet antigen 2, and Zinc transporter 8. More specifically, the present invention relates to an assay comprising a set of at least three recombinant antigen molecules in a single composition, the antigen molecules being selected from the list comprising recombinant human Glutamate decarboxylase 65, recombinant human islet antigen 2, recombinant human Zinc transporter 8, recombinant human insulin, and recombinant human proinsulin. The invention further relates to methods for determining the presence and / or level of at least one autoantibody molecule in a sample from a human subject developing T1D using said recombinant antigen molecules. According to the invention, the presence, absence, or amount of one or more autoantibody molecules against said self-antigens is determined with a luciferase immune precipitation system (LIPS) assay or a modified version of a LIPS assay, i.e., a solid phase capture LIPS (scLIPS) assay.

The invention discloses an immune tolerance realization method based on immune cell negative selection, which comprises the following steps: step 1, separating mononuclear cells from peripheral blood of a patient, and inducing and differentiating the mononuclear cells into DCs in vitro; 2, introducing the Aire gene into DCs by using a virus vector adeno-associated virus (AAV) or a lentivirus; 3, over-expressing Aire protein by the modified DCs, so that the modified DCs can express a plurality of autoantigens; and step 4, injecting the DCs subjected to Aire overexpression back into the body of the patient, and inducing immune tolerance. The preparation method has the beneficial effects that the immune regulation function of DCs is enhanced through the Aire gene, the activity of autoreactive T cells is inhibited, and the damage to pancreatic beta cells is reduced; dependence on a traditional immunosuppressor is reduced, and side effects are reduced; a novel treatment method is provided for autoimmune diseases such as type 1 diabetes, and high safety and specificity are achieved.

A platform for therapy provides: a chimeric molecule comprising one or more auto-antigens linked by a linker to a fluorescent protein; a chimeric molecule comprising three or more components linked by linker, the components comprising two or more auto-antigens of an autoimmune disease and one or more ablative molecule and / or toxin or one or more fluorescent molecules; a chimeric molecule comprising two or more components linked by linker, the components comprising an antibody or an antigen binding fragment thereof to an autoimmune disease associated HLA class or HLA class II molecule and one or more ablative molecules and / or toxins or one or more fluorescent molecules; and a chimeric molecule comprising two or more components linked by linker, the components comprising an antibody or an antigen binding fragment thereof to a disease associated T-cell receptor and one or more fluorescent molecules or one or more ablative molecule and / or toxin

The present invention relates to a chimeric autoantibody receptor (CAAR) capable of targeting immune cells to B cells that produce autoantibodies. The CAAR comprises an autoantigen or a fragment thereof that binds to autoantibodies associated with a neuroautoimmune disease predominantly targeting the central nervous system. The present invention relates to a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid molecule comprising: a sequence encoding an autoantigen or a fragment thereof that binds to autoantibodies associated with a neuroautoimmune disease predominantly targeting the central nervous system; a sequence encoding a transmembrane domain; and a sequence encoding an intracellular signaling domain. In one embodiment, the autoantigen encoded by the nucleic acid sequence comprises or consists of the following: N-methyl-D-aspartic acid receptor (NMDAR) or one or more NMDAR fragments. The present invention further relates to the chimeric autoantibody receptor (CAAR) protein of the present invention, a vector comprising a nucleic acid molecule encoding the chimeric autoantibody receptor (CAAR) of the present invention, a genetically modified immune cell comprising a nucleic acid molecule encoding CAAR, and the use of the immune cell in the treatment or prevention of a neuroautoimmune disease predominantly targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

Chimeric autoantibody receptors (CAARs) can include separate signaling and recognition constructs that are able to bind ligands that target autoantigens made of conventional amino acids, non-conventional amino acids, carbohydrates, or nucleic acids. Additionally, the present disclosure describes cells modified to express such constructs and the use of such constructs and / or cells in the treatment of autoimmune disease.

Disclosed is a protein comprising no more than three human autoantigenic proteins, wherein a first human autoantigenic protein comprises a truncated myelin oligodendrocyte glycoprotein (MOG) amino acid sequence, a second human autoantigenic protein comprises a myelin basic protein (MBP) amino acid sequence, and a third human autoantigenic protein comprises a truncated proteolipid protein (PLP) amino acid sequence. Also disclosed are related nucleic acids, pharmaceutical compositions, methods of treating a demyelinating disease, and methods of producing the proteins.

The present invention provides a method for constructing an animal model of systemic lupus erythematosus, belonging to the technical field of methods for constructing disease animal models. In the present invention, mice GPX4<supgt;fl / wt< / supgt;VilCre+ containing heterozygous GPX4 gene and Cre gene are first obtained, and then SLE induction drugs are used to further induce the mice to develop the disease. In view of the specific gene knockdown in specific cells in the present invention, the etiology of the disease development in the model is clear, that is, the abnormal intestinal barrier system triggers adaptive immune changes, recognizes autoantigens, and ultimately leads to the development of lupus. At the same time, the finally obtained SLE model in the present invention can exhibit higher autoantibodies, lower complement, higher inflammatory factors, and more severe lung damage, and the decrease of intestinal GPX4 in these mice is similar to the intestinal expression characteristics of human SLE.

The present invention discloses the application of human TSHR A subunit in preventing Graves' disease. The present invention orally administers the key pathogenic autoantigen human TSHR A subunit of Graves' disease to neonatal Balb / c mice to induce neonatal oral tolerance to Graves' disease, and explores the dosage of TSHR A subunit. It is found that oral administration of a high dose of TSHR A subunit in the neonatal period can successfully induce immune tolerance of Balb / c female mice to Graves' disease, which provides a new idea and effective basis for the treatment and prevention of Graves' disease and other autoimmune diseases.

The invention provides an MHC class I autoantigen peptide for inducing immune tolerance. The amino acid sequence of the MHC class I autoantigen peptide is shown as SEQ ID NO. 4. The invention also provides a DNA (Deoxyribose Nucleic Acid) molecule for coding the MHC class I autoantigen peptide for inducing immune tolerance. The invention also provides a recombinant vector which contains the DNA molecule. The invention also provides application of the polypeptide in preparation of drugs for preventing or treating autoimmune diseases. The autoantigen peptide provided by the invention is derived from an autoantigen peptide presented on the surface of an activated CD4 + T cell, and can be specifically recognized by a self-reactive CD8 + T cell, so that immune response is induced, and regulation and control on a pathogenic T cell are realized. Through the mechanism, the antigen peptide can be used for inducing immune tolerance of the body, and has application value in improving or treating autoimmune diseases.

The present invention relates to an autoantigen-specific nanofusion vaccine composition for the treatment of systemic sclerosis, the composition being for simultaneous immunomodulation and antifibrosis. A nanofusion body carrying a vimentin peptide according to the present invention was found to inhibit tissue fibrosis in systemic sclerosis, reduce the amount of autoantibodies in serum, and regulate the expression of immune-regulatory cells and pathogenic cells associated with systemic sclerosis. The nanofusion body was also found to inhibit tissue fibrosis and to exhibit enhanced anti-fibrotic effects, when co-administered with a vimentin antibody, in an animal model reflecting the immune status of systemic sclerosis patients. In addition, the nano-vaccine was found to decrease the expression of fibrotic and pathogenic factors in tissues and was also found to improve disease activity not only in vimentin-specific systemic sclerosis but also in infection-associated systemic sclerosis.

Disclosed is a protein comprising no more than three human autoantigenic proteins, wherein a first human autoantigenic protein comprises a truncated myelin oligodendrocyte glycoprotein (MOG) amino acid sequence, a second human autoantigenic protein comprises a myelin basic protein (MBP) amino acid sequence, and a third human autoantigenic protein comprises a truncated proteolipid protein (PLP) amino acid sequence. Also disclosed are related nucleic acids, pharmaceutical compositions, methods of treating a demyelinating disease, and methods of producing the proteins.

The invention pertains to methods and means for the targeted modulation of B-cell mediated immune responses by bringing into contact a B-cell with a specific ratio of soluble single monovalent antigens and complexed multivalent antigens. The targeted modulation of B-cell immunity can be used in mammals for the diagnosis and therapy of various conditions associated with antibody-mediated immunity. Such conditions include proliferative disorders such as cancer, autoimmune disorders, pathogenic infections, inflammatory diseases, allergies and food intolerances. The invention is predicated on the observation that complexed multivalent antigenic structures induce a strong IgG type antibody B-cell response while surprisingly monovalent antigenic structures harbour the ability to suppress such IgG responses, or even induce in the case of autoantigens protective IgM responses, in particular protective oligomeric anti-insulin antibodies. The invention in this regard offers methods, compositions, therapeutics, diagnostics and food additives.

A platform for therapy provides a therapeutic molecule comprising an auto-antigen linked by a linker to a toxin or other ablative molecule. Exemplary auto-antigen is Dsg3 or Dsg1. Other auto-antigens include Dsg1, Dsg3, bullous pemphigoid antigen 180, bullous pemphigoid antigen 230, MuSK, anti-phospholipase A2 Receptor, Factor VIII, one or more protein expressed by a viral vector administered to a subject for gene therapy, a DNA molecule carried by a gene therapy viral vector. A pharmaceutical composition comprising a disclosed therapeutic molecule is disclosed. Methods of treating diseases using the disclosed molecules are disclosed.

The invention discloses an establishment method and application of a type-1 autoimmune hepatitis mouse model, and relates to the technical field of biology, and the technical key points are as follows: an adenovirus is combined with an overexpression Sepsecs plasmid to realize continuous expression of autoantigen in the liver, a chronic liver inflammation model conforming to type-1 AIH characteristics is successfully induced in a mouse body for the first time, and the mouse model has a good application prospect. The model shows clinical pathological characteristics of continuous infiltration of inflammatory cells, abnormal liver function, autoantibody generation, hepatic tissue fibrosis and the like, and has good stability and repeatability. At present, no type 1 AIH mouse model constructed by using the Sepsecs antigen is publically reported at home and abroad, and the technical blank in the field of type 1 AIH chronic animal models is filled. The model can be used for AIH pathogenesis research, autoantigen screening, novel diagnostic marker discovery, immune intervention means evaluation and clinical verification before new medicine, has wide scientific research and industrial application prospects, and provides an ideal experimental animal model platform.

The invention relates to the technical field of biological medicines, and discloses a nuclear autoantigen sperm protein-containing pharmaceutical composition for promoting myocardial regeneration and repair and application of the nuclear autoantigen sperm protein-containing pharmaceutical composition. The nucleotide sequence of the NASP gene is as shown in SEQ ID NO: 1, and the coded amino acid sequence of the NASP gene is as shown in SEQ ID NO: 2. The pharmaceutical composition disclosed by the invention can promote the number of myocardial cells and repair necrotic myocardium on the gene level, so that acute myocardial infarction is improved.

The invention relates to an mRNA (messenger Ribonucleic Acid) vaccine targeting breast cancer cell line neoantigen epitopes as well as a preparation method and application thereof, and belongs to the technical field of tumor mRNA vaccines. According to the invention, new autoantigen epitopes are obtained by mutation screening in tumor cells through biosignal analysis, and the new autoantigen epitopes show better immunocompetence when being applied to mRNA vaccines.

The invention relates to a diagnostic kit and methods for detecting and quantifying autoantibodies associated with the onset of type 1 diabetes (T1D). The kit comprises recombinant antigen molecules fused to bioluminescent reporter proteins for the detection of autoantibodies directed against self-antigens expressed by pancreatic islet beta cells. The presence, absence, or amount of one or more autoantibody molecules against said self-antigens is determined with a luciferase immune precipitation system (LIPS) assay or a modified version of a LIPS assay, i.e., a solid phase capture LIPS (scLIPS) assay.

A novel treatment for Graves' Disease (GD) is disclosed and described. Chimeric autoantigen receptor (CAAR) T cells are engineered using a CAAR construct causing thyroid stimulating hormone receptor (TSHR) epitope expression such that the engineered CAAR T cells serve as bait for autoreactive B cells. The engineered CAAR T cells specifically eliminate the autoreactive B cells, thus eliminating the causative factor for GD. Certain CAAR T cells are further engineered to incorporate bispecific LINK CAR technology to further require the presence of CD19 or BCMA to further increase CAAR T cell targeting specificity to autoreactive B cells and plasma cells.

The invention provides an antibody which can competitively inhibit an autoantibody, effectively prevent or treat immune diseases related to decline of the function of an autoantigen, and has no side effect. Meanwhile, the invention also provides a pharmaceutical composition which contains the antibody and is used for treating immune diseases.