148 results about "HMGB1" patented technology

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to a vertebrate high mobility group box (HMGB) polypeptide, methods of detecting and / or identifying an agent that binds to an HMGB polypeptide, methods of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade and methods of detecting an HMGB polypeptide in a sample.

Disclosed is a novel NASH marker for use in a method for detecting NASH or evaluating the severity of NASH, which utilizes at least one factor selected from the group consisting of an IL-1 receptor antagonist, sCD40, HMGB1, sPLA2 group IIA and an sPLA2 activity as the marker. Also disclosed is a method for detecting NASH or evaluating the severity of NASH in a subject, which utilizes the marker.

The present invention relates to novel immunogenic compositions (e.g., vaccines), the production of such immunogenic compositions and methods of using such compositions. More specially, this invention provides unique immunogenic molecules comprising an HMGB1 polypeptide (e.g., an HMGB1 B-box polypeptide) and an antigen. Even more specifically, this invention provides novel fusion proteins comprising an isolated HMGB1 polypeptide and an antigen such that administration of these fusion proteins provides the two signals required for native T-cell activation.

In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to a vertebrate high mobility group box (HMGB) polypeptide, methods of detecting and / or identifying an agent that binds to an HMGB polypeptide, methods of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade and methods of detecting an HMGB polypeptide in a sample.

Disclosed herein are methods and devices for stimulating an immune response to a disease in a subject, which involves passing sub-microsecond long pulses of electric fields having an amplitude between 5 kV / cm and 68 kV / cm through an abnormal growth of a subject sufficient to suppress myeloid-derived suppressor cell (MDSC) or regulatory T cell (Treg) production, increase adenosine triphosphate (ATP) or high mobility group box 1 (HMGB1) production, or stimulate dendritic cell activation in the subject.

Use of the protein HMGB1 or a variant or fragment thereof or a polynucleotide encoding therefor for inducing the activation of an antigen presenting cell (APC).

Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and / or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.

Methods and compositions are disclosed for protecting an organ or tissue from inflammation and organ injury following ischemia, reperfusion, and trauma through the administration of an HMGB1 protein within a time period sufficient to protect the organ or tissue from injury.

It is described a composition comprising an effective amount of the HMGBl protein or functional parts thereof, of HMGBl expressing vectors, for the treatment of tissue damage and / or to promote tissue repair and regeneration. It is further described a composition comprising an effective amount of an antagonist of the HMGBl protein for the treatment of adverse effects induced by necrotic tissue, such as recruitment and activation of mveloid cells, loss of the barrier function of endothelia, edema.

The present technology provides methods and compositions for the treatment of tissue-damage related immune dysregulation by administering a composition comprising one or more of CD24; CD24 fragments, variants and derivatives, CD24Fc fusion proteins; HMBG1-binding proteins, binding proteins to HMBG1 Box B; antagonists of HMGB1, polyclonal, monoclonal, recombinant, chimeric, humanized scFv antibodies and antibody fragments to HMGB1 or fragments of HMGB1 and antibodies that bind and suppress the activity of HMGB1 Box B; Siglec 10 agonists such as anti-Siglec 10 antibodies; and combinations thereof to a patient.

The present invention for the first time demonstrated that:(1) bone marrow-derived pluripotent tissue stem cells can be induced in peripheral blood by intravenously administering tissue extract prepared from isolated skin pieces;(2) the substance in the isolated skin pieces, which is responsible for mobilizing bone marrow-derived pluripotent tissue stem cells to peripheral blood, is HMGB1; and(3) HMGB1 with the activity of mobilizing bone marrow-derived pluripotent stem cells to peripheral blood can be easily purified from cultured cells.

The present invention for the first time demonstrated that:(1) bone marrow-derived pluripotent tissue stem cells can be induced in peripheral blood by intravenously administering tissue extract prepared from isolated skin pieces;(2) the substance in the isolated skin pieces, which is responsible for mobilizing bone marrow-derived pluripotent tissue stem cells to peripheral blood, is HMGB1; and(3) HMGB1 with the activity of mobilizing bone marrow-derived pluripotent stem cells to peripheral blood can be easily purified from cultured cells.

The invention provides a thrombin activity based chimeric peptide with double targeting effects, a preparation method and an application thereof. The chimeric peptide provided by the invention contains three segments: segment 1 has an amino acid sequence having 20th to 90th amino acid from N-terminal of HMGB1 protein; segment 2 has an amino acid sequence of Exendin-4 protein; and segment 3 which contains cleavage sites of thrombin and dipeptidyl peptidase is a junction fragment of segment 1 and segment 2. According to the preparation method provided by the invention, the thrombin activity based chimeric peptide with double targeting effects can be obtained by synthesis of a polypeptide synthesis technology or construction of an expression vector which contains nucleotide sequence encoding the chimeric peptide, expression of the protein in a gene engineering strain and purification of the protein. The chimeric peptide provided by the invention has double targeting effects of inhibiting inflammatory response and decreasing blood glucose, and can be applied in the preparation of anti-inflammatory and / or hypoglycemic drugs.

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn s disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

The invention belongs to a biological dosemeter of ionizing radiation, in particular to application of high mobility group box 1 (HMGB1) as a biological dosemeter of ionizing radiation. After isolated cells especial blood is radiated, the increase of HMGB1 content is proportional to received ionizing radiation dose to form certain dose-effect relation, and the ELISA (Enzyme-Linked Immuno Sorbent Assay) method and other simple, convenient and feasible methods can be adopted for rapid detection after 24 h of irradiation. Thus, the HMGB1 can be used as the biological dosemeter of ionizing radiation; moreover, the HMGB1 can be used for measuring the biological radiation dose of human bodies and animals exposed to ionizing radiation.

Compositions and methods for modulating human immunodeficiency virus (HIV) infection involving substances that inhibit the ability of high mobility box 1 (HMGB1) protein to interact with natural killer (NK) cells. Therapeutic compositions comprising antibodies and drugs, such as glycyrrhizin, which bind to HMGB1. Methods of detecting or monitoring HIV infection involving detection or quantitation of HMGB1 or antibodies specific for HMGB1 in a biological sample.

A fragment peptide having a proper length composed of a part of an HMGB1 protein was synthesized and the peptide was confirmed to exhibit therapeutic effects on myocardial infarction.

Methods of identifying specific target molecules for design of anti-angiogenic and vascular targeting approaches are disclosed. Transcriptional profiles of tumor endothelial cells were compared with that of normal resting endothelial cells, normal but angiogenically activated placental endothelial cells, and cultured endothelial cells. Although the majority of transcripts were classified as general angiogenesis markers, 17 genes were identified that show specific overexpression in tumor endothelium. Antibody targeting of four cell-surface expressed or secreted products (vimentin, CD59, HMGB1 and IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. The results demonstrate the utility of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.

It is described a method to promote stem cell migration and / or proliferation in cell culture or in vivo comprising the step of exposing such cells to an effective amount of the HMGB1 protein or its active fragment.

Compositions and methods for modulating human immunodeficiency virus (HIV) infection involving substances that inhibit the ability of high mobility box 1 (HMGB1) protein to interact with natural killer (NK) cells. Therapeutic compositions comprising antibodies and drugs, such as glycyrrhizin, which bind to HMGB1. Methods of detecting or monitoring HIV infection involving detection or quantitation of HMGB1 or antibodies specific for HMGB1 in a biological sample.

A method of screening a small molecule compound for use in treating unipolar depression, comprising screening a test compound against a target selected from the group consisting of the gene products encoded by ADCYAP1R1, HMGB1, MIP, NIPSNAP3A, SRC, WFS1, CLIC6, GABRR3, KDR, PKD1L1, ADARB2, MAP3K1, PPARGC1A, DRD3, PTHR1, BF, CART, CLCN7, EDIL3, GPR73L1, PAQR8, USP2, CCL5, GABBR1, AADACL1, CDK4, DPP4 / SLC4A10, FCER2, FZD5, LOC197350, MS4A8B, NOS2A, NTSR1, PSMA4, SREBF1, TAAR2 / TAAR3, TLR10, or TPCN1, where activity against said target indicates the test compound has potential use in treating unipolar depression.

The present invention relates to HMGB1 variants that maintain HMGB1 wild type chemoattractant function while displaying abolished cytokine and / or chemokine stimulating properties. Such molecules are useful in therapy.

The invention discloses a plasmid for silencing cytokine signal inhibitory factor 1 and expressing high mobility group B1 protein and tumor associated antigen and a preparation method thereof, which belongs to genetic engineering technology. According to the invention, based on a gene recombination method, a cytokine signal inhibitory factor 1 small interfering RNA fragment shSOCS1, a fusion genecoding sequence of NY-ESO-1and MAGE3, and a coding sequence of HMGB1 are connected in the same vector of pIRES-EGFP; respective expression is guaranteed to be correct; and a plasmid coexpressing shSOCS1, HMGB1 and tumor associated antigen is constructed. A new-generation dendritic cell vaccine prepared by the plasmid of the invention can induce high-efficiency immune response of CTL cells with almost no side effects, and can become safe and effective immunotherapy.

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.