126 results about "TLR2" patented technology

Methods are disclosed for treating an inflammatory skin condition in a subject. The methods comprise administering to a subject an HMGB antagonist, such as a high mobility group box (HMGB) A box or a biologically active fragment thereof, an antibody to HMGB or an antigen-binding fragment thereof, an HMGB small molecule antagonist, an antibody to TLR2 or an antigen-binding fragment thereof, a soluble TLR2 polypeptide, an antibody to RAGE or an antigen-binding fragment thereof, a soluble RAGE polypeptide and a RAGE small molecule antagonist.

An intraorally administrable vaccine composition useful to be a preventive or therapeutic agent for infectious diseases, and effectively induces a systemic immune response or a mucosal immune response is provided. A vaccine composition for administration to the oral cavity of a human or an animal, the vaccine composition containing at least one antigen derived from an infectious disease, and at least one selected from the group consisting of a toll-like receptor 4 (TLR4) agonist, a toll-like receptor 2 / 6 (TLR2 / 6) agonist, and cyclic dinucleotide, or a derivative or salt thereof.

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and / or reduce host immunity and / or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and / or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The invention relates to the field of tumor cellular immunotherapy, and in particular relates to a recombinant lentivirus and application thereof. The recombinant lentivirus comprises a chimeric antigen receptor, wherein the chimeric antigen receptor mainly comprises signal peptide, an antigen recognition domain, a transmembrane domain, an intracellular co-stimulation signal transduction domain and a CD3 zeta signal transduction domain which are serially connected; the intracellular co-stimulation signal transduction domain mainly comprises a human TLR2 (Toll Like Receptor 2) intracellular domain. A GPC3 CAT T (Glypican 3 CAT T) cell prepared from the recombinant lentivirus has an intense cell killing effect on liver cancer cells, a Th1 cell factor can be highly expressed, a tumor killing effect caused by non-CAR T (Chimeric Antigen Receptor T) cell can be stimulated to the maximum extent, escape and potential reoccurrence risk of GPC 3-tumor cells can be effectively prevented, the tumor cells can be killed by T cells expressing the chimeric antigen receptor, normal tissue can be slightly damaged, a tumor immunosuppression micro environment can be broken through, and thus a relatively good treatment effect on solid tumor can be achieved.

This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and / or subtypes of Crohn's disease (CD) and / or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and / or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and / or treatment of IBD, including CD and / or UC.

The discovery of Toll-like receptors (TLRs) on the surface of hematopoietic cells provides new methods for the stimulation and differentiation of various classes of progenitor cells. TLR2 and TLR4 agonists (natural ligands, mimetics, antibodies) are particularly useful in these methods. The cells can be isolated and used for various purpose including tissue regeneration and grafting. In contrast, antagonists of TLRs can be used to protect cells from various insults such as chemo- and radiotherapy, acute and chronic infection, and transplantation by inhibiting activation and differentiation. TLR2, TLR4 and TLR9 pathway antagonists (soluble TLR, mimetics, antibodies) are particularly useful in these methods. Cells can be isolated and used for various purposes including transplantation.

The invention provides compositions comprising liposomes, an antigen capable of inducing a humoral immune response, a carrier comprising a continuous phase of a hydrophobic substance, and an adjuvant that activates or increases the activity of TLR2. The invention also provides uses for such compositions in inducing a humoral response and methods for their use in the treatment of a disease, disorder or ailment ameliorated by a humoral immune response.

Disclosed are compositions, including LcrV antigenic polypeptides, vaccines and antibodies, as well as associated methods for treating and / or preventing Yersinia infection in a host. The invention further provides immunomodulatory LcrV proteins and polypeptides comprising TLR2 and IFN-gammaR-IFN-gamma-binding sequences that stimulate host anti-inflammatory responses and repress pro-inflammatory responses.

Antisense oligonucleotide compounds, compositions and methods for downregulating TLR2 expression are provided. The composition comprises an antisense oligonucleotide targeted to a nucleic acid encoding TLR2. The composition may also comprise an antisense oligonucleotide targeted to a nucleic acid encoding TLR2 in combination with other therapeutic and / or prophylactic compounds and / or compositions. Methods of using these compounds and compositions to downregulate TLR2 expression and prevent or treat diseases that would benefit from modulating TLR2 expression are provided.

The invention discloses ginseng derived nano-particles, as well as a preparation method and application thereof. The ginseng derived nano-particles have a membrane structure, wherein the particle size range is 150 to 500nm, and the peak particle size is 280 to 350nm. The ginseng derived nano-particle is prepared by performing centrifugation and filtering impurity removal for many times. By the ginseng derived nano-particle, a bone marrow derived monocyte-macrophage can be effectively induced to be proliferated and activated, meanwhile, multiple surfactant molecules such as a TLR2 / 4 (toll-like receptor 2 / 4) and a CD80 (cluster of differentiation 80) are up-regulated, and cell factors such as a TNF-a (tumor necrosis factor-a) and an IL-6 (interleukin-6) are secreted. The ginseng derived nano-particle has broad application prospect in development of a medicament for preparing a natural immunoenhancer.

An intraorally administrable vaccine composition useful to be a preventive or therapeutic agent for infectious diseases, and effectively induces a systemic immune response or a mucosal immune response is provided. A vaccine composition for administration to the oral cavity of a human or an animal, the vaccine composition containing at least one antigen derived from an infectious disease, and at least one selected from the group consisting of a toll-like receptor 4 (TLR4) agonist, a toll-like receptor 2 / 6 (TLR2 / 6) agonist, and cyclic dinucleotide, or a derivative or salt thereof.

The invention discloses an exosome and a preparing method and application thereof, and relates to the field of exosome medicines. In order to solve the problem of postoperative cognition dysfunction,mesenchymal stem cells are separated out of cornu cervi tissue; after culturing, a cell culture solution is collected, and the exosome from cornu cervi mesenchymal stem cells are extracted through separation. It is proved that CPB rat nerve function deficit and oxidative stress response can be relived, a protection effect is realized for CPB rat nerve cell apoptosis and CPB rat POCD can be relieved through a TLR2 / TLR4 signal channel. The exosome can be used for preparing medicines for improving or treating the cognition dysfunction.

The invention provides a chimeric antigen receptor targeting GPC3 and an application of the chimeric antigen receptor. The chimeric antigen receptor comprises an antigen binding structural region, a hinge region, a transmembrane structural region and a signal transduction structural region, wherein the antigen binding structural region is an anti-GPC3 single-chain antibody; the hinge region is IgG4-CH3; and the signal transduction structural region is a combination of a CD28 intracellular region, CD3 zeta, and TLR2. The IgG4-CH3 is adopted as the hinge region of the chimeric antigen receptor,the CD28 intracellular region, the CD3 zeta and the TLR2 which are connected in series are adopted as the signal transduction structural region of the chimeric antigen receptor, the hinge region and the signal transduction structural region cooperate with each other, in-vitro amplification of CD4 + CAR-T cells is promoted, and cell signals transmitted by an extracellular region are expanded. The killing effect of the CAR-T cells is enhanced.

The present invention provides modified TLR2 ligands useful for modulating inflammatory responses. In particular, the ligands comprise (a) a fatty acid di- or tri-linoleate and (b) a GM1-binding peptide. The linoleate provides the anti-inflammtory function, while the GM1-binding peptide facilitates endocytosis.

The invention provides a chimeric antigen receptor T cell targeting BCMA and application of the chimeric antigen receptor T cell. A chimeric antigen receptor comprises a signal peptide, an antigen binding structural domain, a transmembrane structural domain and a signal transduction structural domain, Wherein the antigen binding domain comprises an anti-BCMA single-chain antibody; and the signal transduction structural domain comprises 4-1BB, CD3 [zeta] and TLR2. According to the chimeric antigen receptor T cell, 4-1BB, CD3[zeta] and TLR2 which are connected in series are used as signal transduction structural domains of the chimeric antigen receptor, and are matched with a specific antigen binding structural domain anti-BCMA single-chain antibody, so that the constructed chimeric antigenreceptor T cell has remarkably enhanced capability of specifically recognizing and killing BCMA positive tumor cells, and is high in safety, and bright clinical application prospects are realized in the field of B cell malignant tumor treatment.

The invention relates to the field of biomedicines, in particular to application of zymosan-A or derivative thereof in preparing a medicine for protecting acute radioactive bone marrow injury. The application is characterized in that after proofed by mouse in-vivo experiment, the zymosan-A can obviously reduce the injury degree to a bone marrow hematopoietic system due to ionizing radiation, promote the restoration of the hematopoietic system, and inhibit the decreasing of peripheral blood leucocyte caused by the ionizing radiation; after proofed by in-vitro cytology experiments, the zymosan-A can reduce the cell withering rate after radiation, and improve the cell proliferation ability after radiation; after proofed by TLR2 knocking the mouse, the zymosan-A can play the radiation protecting function after activating a TLR2 signal channel in a targeting way; after proofed by the experiments, the zymosan-A can decrease the radioactive injury of the bone marrow hematopoietic system of the mouse via activating the TLR2 signal channel, and protect the peripheral blood leucocyte, so that a new reference is provided for the zymosan-A protecting the acute radioactive bone marrow injury.

The discovery of Toll-like receptors (TLRs) on the surface of hematopoietic cells provides new methods for the stimulation and differentiation of various classes of progenitor cells. TLR2 and TLR4 agonists (natural ligands, mimetics, antibodies) are particularly useful in these methods. The cells can be isolated and used for various purpose including tissue regeneration and grafting. In contrast, antagonists of TLRs can be used to protect cells from various insults such as chemo- and radiotherapy, acute and chronic infection, and transplantation by inhibiting activation and differentiation. TLR2, TLR4 and TLR9 pathway antagonists (soluble TLR, mimetics, antibodies) are particularly useful in these methods. Cells can be isolated and used for various purposes including transplantation.

The invention discloses a duck TLR2 extracellular region polyclonal antibody as well as a preparation method and application thereof. The method comprises the following steps: (1) artificially synthesizing a TLR2 extracellular region sequence; (2) constructing the TLR2 extracellular region sequence to an expression carrier pET28a and screening to obtain recombinant plasmid pET28a-TLR2; (3) converting recombinant plasmid pET28a-TLR2 to Escherichia coli BL21 and expressing TLR2-His recombinant protein in the Escherichia coli BL21; (4) utilizing the TLR2-His recombinant protein to immunize domestic rabbits and separating immunized domestic rabbit serum to obtain the duck TLR2 extracellular region polyclonal antibody. The serum titer of the prepared polyclonal antibody disclosed by the invention exceeds 1 to 50000, the polyclonal antibody has the characteristics of good specificity and high purity, recombinant protein and tissue endogenous TLR2 can be specifically detected, and the prepared polyclonal antibody provides advantageous conditions for further researching biological functions of TLR2.

The invention provides compositions comprising liposomes, an antigen capable of inducing a humoral immune response, a carrier comprising a continuous phase of a hydrophobic substance, and an adjuvant that activates or increases the activity of TLR2. The invention also provides uses for such compositions in inducing a humoral response and methods for their use in the treatment of a disease, disorder or ailment ameliorated by a humoral immune response.

The invention provides a CD19 and CD22 double-target chimeric antigen receptor T cell and application thereof. The chimeric antigen receptor T cell expresses a chimeric antigen receptor which is specifically combined with CD19 and CD22, wherein the chimeric antigen receptor comprises a signal peptide, an antigen binding structural domain, a transmembrane structural domain and a signal transductionstructural domain; the antigen binding structural domain comprises an anti-CD19 single-chain antibody and an anti-CD22 single-chain antibody; and the signal transduction structural domain is 4-1BB, CD3 zeta and TLR2. According to the invention, 4-1BB, CD3zeta and TLR2 which are connected in series are used as a signal transduction structural domain of the chimeric antigen receptor to construct the CD19 and CD22 targeting double-target CAR-T cell, and the CAR-T cell has efficient CD19 and CD22 targeting activity and killing ability, and is beneficial to avoiding immune escape phenomenon.

Antisense oligonucleotide compounds, compositions and methods are provided for down regulating the expression of TLR2. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding TLR2. The compositions may also comprise antisense oligonucleotides targeted to nucleic acids encoding TLR2 in combination with other therapeutic and / or prophylactic compounds and / or compositions. Methods of using these compounds and compositions for down-regulating TLR2 expression and for prevention or treatment of diseases wherein modulation of TLR2 expression would be beneficial are provided.

The invention provides a method for identifying pure Hareford bulls and hybrid Hareford bulls, which is to determine if a Hareford bull is pure or hybrid or of other variety by detecting the loci from 300bp to 307bp in a promoter area 627bp of a TLR2 gene of the bull. The method has the characteristics of simplicity, high speed, accuracy, reliability, low cost and the like and has high practicality. The method of the invention has a promising application prospect in Hareford bull introduction, Hareford import and export trade, local crossbreeding improvement, beef cattle novel variety breeding, beef product molecular marking and tracking and the like.

The invention provides carbohydrate based compounds, methods of preparation, and compositions useful for modulating signaling through Toll-like receptors. The methods involve contacting a TLR-expressing cell with a carbohydrate based compound of the invention having a core structure comprising of one or more sugar moieties. The carbohydrate based compounds are useful for inhibiting immune stimulation involving TLR ligands, especially TLR4 and TLR2. The compounds also are suitable for inhibition of inflammatory conditions resulting from infections. The compounds have use in the treatment of inflammation, autoimmunity, allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer, and immunodeficiency.

The present invention provides a pro-inflammatory synthetic polysaccharide antigen (SPA), or a pharmaceutically acceptable salt thereof, comprising a TLR2-targeting synthetic peptidoglycan (PGN) moiety onto which a first epitope and a second epitope are each covalently attached. The first epitope comprises one or more than one generic T helper peptide sequence, and the second epitope comprises one or more than one target epitope. The first and second epitopes are present in one or more copies each within the SPA. Each target epitope is a peptide sequence or a carbohydrate moiety, and is an immunogen to CD8+ T cells or B cells. The present invention also provides a suppressive synthetic polysaccharide antigen (SPA), or a pharmaceutically acceptable salt thereof, comprising a TLR2-targeting synthetic peptidoglycan (PGN) moiety onto which one or more than one target epitope is covalently attached. Each target epitope is a peptide sequence or carbohydrate moiety and is present in one or more copies within the SPA.

The present disclosure relates to compositions and methods of modulating inflammatory and immune responses through binding of SAA to TLR2 in a subject (e.g., human, non-human primate, rodent, etc.), and compositions and methods for screening TLR2 agonists and antagonists. In the studies described herein, a potential role of SAA in neutrophilia was investigated and the results demonstrated that SAA is a potent inducer for macrophage secretion of G-CSF, which leads to neutrophilia in mice. Using G-CSF− / − and TLR2− / − mice, it was found that the SAA-induced neutrophilia is dependent on TLR2-mediated production of G-CSF. Based on direct binding assay and gain-of-function studies in TLR2-transfected cells, SAA was identified as a novel ligand for TLR2 and a link between increased SAA concentration and TLR2-mediated inflammatory responses such as neutrophilia was established. Additional embodiments are disclosed.

The present invention discloses an anti-TLP2 antibody. Said anti-TLR2 antibody can inhibit tumor, specially can inhibit the metastasis of B16 melanin tumor. Said anti-TLR2 antibody not only can block TLR2 activity, but also can obviously reduce number of metastatic foci of lung. At the same time, said invention finds that the bleomycin and said anti-TLR2 antibody have good synergistic action.

The invention provides an enhanced MUC1 targeting chimeric antigen receptor and an application thereof. The chimeric antigen receptor comprises an antigen binding structural domain, a transmembrane structural domain and a signal transduction structural domain, wherein the antigen binding structural domain comprises an anti-MUC1 single-chain antibody and the signal transduction structural domain comprises 4-1BB, CD3 [zeta] and TLR2. The chimeric antigen receptor disclosed by the invention not only has a targeting effect on MUC1 positive tumor cells, but also can efficiently activate T cells, eliminate the immunosuppressive effect of regulatory T cells and promote the formation of memory T cells, and the constructed T cells for expressing the chimeric antigen receptor have remarkably enhanced tumor cell killing capacity.

The invention provides a preparation method for maca polysaccharide and preliminary study on immunoregulatory activity thereof. The maca polysaccharide of a relatively high purity is extracted and separated by various means such as boiling water extraction, ethanol precipitation and passing DEAE-52 cellulose resin. Mmonosaccharide is detected to comprise glucose and arabinose with a molar ratio of (4-10): 1 and the molecular weight of the monosaccharide is 10000-30000Da. Meanwhile, the polysaccharide extracted by the method provided by the invention has certain promoting action on activity of a mouse macrophage RAW264.7 and expression of TLR4, TLR2 and an inflammatory factor of the mouse macrophage. The invention has characteristics that the process flow is simple, the operation is easy, the cost is relatively low, and large-scale production is facilitated; the polysaccharide extracted by the method provided by the invention has functions of preventing and resisting cancers, resisting aging, resisting oxidization, resisting autoimmune diseases and the like, thereby providing a theoretical basis for further researching and developing polysaccharide new drugs.

This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and / or subtypes of Crohn's disease (CD) and / or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and / or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and / or treatment of IBD, including CD and / or UC.