106 results about "TLR9" patented technology

The invention provides methods of inducing an immune response to cancer comprising co-administering to a cancer patient one or more TLR9 agonists and one or more checkpoint inhibitors. Preferably, the one or more TLR9 agonists are administered to the patient via intratumoral (i.t.) administration.

The invention relates to TLR9 antagonist compounds and their therapeutic or prophylactic use. The invention provides novel immune regulatory oligonucleotides and immunomers as antagonist of TLRs and methods of use thereof. These immune regulatory oligonucleotides have unique sequences that suppress, without completely ablating, TLR-mediated signaling in response to a TLR ligand or TLR signaling agonist. The methods may have use in the prevention and treatment of autoimmunity, inflammation, inflammatory bowel disease, lupus, allergy, asthma, infection, sepsis, cancer and immunodeficiency.

The instant invention is to provide a method for detecting and measuring malaria infection utilizing the induction by hemozoin (HZ); a method for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection using the method for detecting and measuring; and a means for regulating the induction of innate immunity using the HZ, synthetic HZ, or derivatives thereof as an adjuvant or immunostimulant. Malaria infection is detected and measured of by detecting and measuring HZ-induced, TLR9-mediated, and MyD88-dependent innate immune activity. The detection and measurement of malaria infection can be used to diagnose malaria infection. The method for detecting and measuring is also used for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection. Further, HZ, synthetic HZ, or derivatives thereof are used as an adjuvant or immunostimulant to regulate HZ-induced innate immune induction.

The present invention relates to the combination therapy of antibodies against human CSF-1R with a TLR9 agonist.

The present invention relates to the combination therapy of antibodies against human CSF-1R with a TLR9 agonist.

The present invention provides a heterocyclic compound having a TLR7, TLR9, TLR7 / 8, TLR7 / 9 or TLR7 / 8 / 9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases, inflammatory diseases and the like, in particular, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.

The present disclosure provides methods of inhibiting an immune response to a viral vector used in gene therapy, such as adeno-associated virus (AAV), which involves co-administration of viral vector and an interfering molecule. The interfering molecule functions by either disrupting the TLR9-MyD88-type I IFN signaling pathway and / or neutralizing Type I IFNs, thereby inhibiting the immune response directed against the viral vector. The methods additionally encompass the step of re-administering the viral vector.

The invention relates to TLR9 antagonist compounds and their therapeutic or prophylactic use. The invention provides novel immune regulatory oligonucleotides and immunomers as antagonist of TLRs and methods of use thereof. These immune regulatory oligonucleotides have unique sequences that suppress, without completely ablating, TLR-mediated signaling in response to a TLR ligand or TLR signaling agonist. The methods may have use in the prevention and treatment of autoimmunity, inflammation, inflammatory bowel disease, lupus, allergy, asthma, infection, sepsis, cancer and immunodeficiency.

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.

Embodiments of the invention are directed to methods of treating, inhibiting or attenuating a microbial infection in an individual who has or is at risk for developing such an infection, comprising the step of administering an effective amount of a TLR9 agonist and a TLR 2 / 6 agonist to the individual.

An oligonucleotide with a nucleotide sequence of 5′-cctcctcctcctcctcctcctcct-3′ (SEQ ID NO: 1) inhibits proliferation of human PBMC activated by TLR9 agonist and interferon production from human PBMC induced by TLR9 agonist, HSV-1, flu virus and serum from SLE patients, and rescues the mice from cytokine-mediated lethal shock. This oligonucleotide can be used as a remedy for the treatment of systemic lupus erythematosus (SLE), sepsis, multiple organ dysfunction syndromes and other immune-mediated disorders.

The present invention provides a heterocyclic compound having a TLR7, TLR9, TLR7 / 8, TLR7 / 9 or TLR7 / 8 / 9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases, inflammatory diseases and the like, in particular, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.

The invention provides the use of immune regulatory oligonucleotides (IRO) as antagonist of TLRs and potentiators of anti-inflammatory agents that inhibit TNF for the prevention and treatment of inflammatory and autoimmune diseases.

The present invention provides methods and kits for prognosing the progression of fibrosis in a subject having fibrosis, as well as methods for identifying a compound that can slow down the progression of fibrosis in a subject having fibrosis, methods of monitoring the effectiveness of a therapy in reducing the progression of fibrosis in a subject having fibrosis, methods of selecting a subject for participation in a clinical trial for the treatment of fibrosis, and methods for inhibiting progression of fibrosis in a cell or a subject having fibrosis. The methods are based on determining the level of Toll-like recepter 9 (TLR9).

A molecule or molecule complex capable of binding to TLR9 and to CD32 comprising at least one epitope of at least one antigen, and its use a medicament for the treatment of allergies.

Cell surface TLR9 and TLR9 ligand binding agents are disclosed. The binding agents include antibodies and other proteins. The binding agents are useful as therapeutics, diagnostics or research reagents.

The present invention discloses a compound adjuvant for tuberculosis subunit vaccine, containing cationic liposome dimo-thylidioctyl ammonium bromide (DDA), TLR9 ligand CpG oligodeoxynucleotides 2395 and TLR3 ligand PolyICLC, and also provides the tuberculosis subunit vaccine and preparation method and application thereof. The beneficial effect of the invention is that the compound adjuvant for tuberculosis subunit vaccine provided by the present invention enhances the immunogenicity of the fusion protein of Mycobacterium tuberculosis, contributing to the induction of the tuberculosis fusion protein to Th1-type anti-tuberculosis immune response.

The present invention relates, inter alia, to methods and compositions for regulating the host response to biomaterials, including inhibiting inflammation from and rejection of biomaterials using salicylate compounds and / or TLR7 / TLR9 antagonists as described herein.

The invention provides an HPV (human papillomavirus) peptide / DC (dendritic cell) mixed vaccine prepared in the presence of a TLR (toll-like receptor) agonist. The mixed vaccine comprises one part of HPV11E77-15, one part of mouse bone marrow-derived dendritic cells which are cultured in vitro and one part of TLR9 agonist as an adjuvant, wherein the dendritic cells are extracted from mouse bone marrow and further cultured in vitro, the co-incubation with one section of HPV11E7CTL (cytotoxic T lymphocyte) epitope peptide with strongest immunogenicity is firstly carried out, the co-incubation with the TLR ligand CpG and the like is further respectively carried out for promoting the maturation of the DC, the degree of maturation can be confirmed by detecting the change of a marker on the surface of the DC after incubation, and the DC vaccine which is simulated to mature can be used for immunizing mice. The TLR ligand and the HPV11E7 peptide are utilized jointly to promote the degree of maturation of the DC, the level of TNF-alpha (tumor necrosis factor-alpha) and IFN-gamma (immunoreactive fibronectin-gamma) of factors of secretory cells of T cells can be particularly improved after combination of the CpG, and the HPV peptide / DC mixed vaccine can be used for preventing and treating genital warts and cervical cancer.

A molecule or molecule complex capable of binding to TLR9 and to CD32 comprising at least one epitope of at least one antigen, its production and its use a medicament, especially for the treatment of allergies.

Embodiments of the invention are directed to methods of treating, inhibiting or attenuating a microbial infection in an individual who has or is at risk for developing such an infection, comprising the step of administering an effective amount of a TLR9 agonist and a TLR 2 / 6 agonist to the individual.

The invention relates to a medicine for treating psoriasis. The medicine is prepared from a phosphorothioate modified molecule preparation and phosphate buffer, wherein the phosphorothioate modified molecule preparation is used as the active ingredient and has the sequence shown in SEQ ID NO:1. The medicine can resist activation of TLR7 / 8 and TLR9, restrain release of proinflammatory factors such as TNF and IL, and achieve an inflammation restraining effect. By means of a surface microneedle system, micropores penetrating through a cuticle are established without causing the pain feeling, the medicine smoothly enters affected parts through inunction and is diffused in corium layers, activation of aggregated immune cells is prevented, and the pathological injury by psoriasis can be remarkably relieved.

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.

Modified viral genomes are able to reduce induction of inflammatory and immune anti-viral responses. This manifests itself in reduced NF-kB activity, increased viral transduction rates, and increased expression of transgenes. Viral genomes are modified by incorporating one or more oligonucleotide sequences which are able to bind to TLR9 but not induce activation of it. The oligonucleotide sequences may be synthetic, bacterial, human, or from any other source.

The invention relates to a meningococcus vaccine comprising a chemical conjugate of meningococcus capsular polysaccharide and carrier protein, and a first adjuvant, wherein the first adjuvant is oligodeoxynucleotide comprising at least one non-methylation CpG dinucleotide, and the length of the oligodeoxynucleotide is 15-35 ribonucleotides. The adjuvant used for increasing the immunization effect of the meningococcus vaccine is a novel human vaccine adjuvant with favorable potential application prospect, and the chemical essence of the adjuvant is the oligodeoxynucleotide which is synthesized manually and contains the CpG dinucleotide. By a receptor TLR9 activated immune system on immune cells, the adjuvant reinforces specific immune response aiming at vaccine antigens. The immunization effect of a vaccine can be increased by adding the vaccine adjuvant into the vaccine, so that the dosage of the vaccine antigen can be reduced, the immunization injection times can be reduced and the vaccine cost can be reduced.

The invention belongs to the field of molecular biology, and discloses an siRNA segment capable of inhibiting mouse TLR9 expression and a vector built on the basis of the segment. A sequence of the siRNA segment is 5'-UGUAAGAACUUCAAGUUCA-3'; two Oligo single strands of which two corresponding ends have BamHI and Hind III restriction enzyme cutting sites are synthesized according to the sequence, and are annealed continuously and connected to the vector to build an interference vector pSilencerTM4.1-siRNA9.1. Specific examples, such as RT-PCR, western blot and the like, validate that the interference vector can be used for inhibiting the expression of a mouse Raw264.7 cell TLR9 and block a signal channel caused by the TLR9 successfully and specifically. Therefore, the siRNA9.1 sequence and the interference vector obtained by the siRNA9.1 sequence can be used for obtaining a large number of mouse cells with low TLR9 expression cells and blocking the TLR9 signal channel economically, fast and conveniently.

The invention relates to a poliomyelitis vaccine comprising an inactivated poliomyelitis virus used as an antigen, and a first adjuvant, wherein the first adjuvant is oligodeoxynucleotide comprising at least one non-methylation CpG dinucleotide, and the length of the oligodeoxynucleotide is 15-35 ribonucleotides. The adjuvant used for increasing the immunization effect of the inactivated poliomyelitis vaccine is a novel human vaccine adjuvant with favorable potential application prospect, and the chemical essence of the adjuvant is the oligodeoxynucleotide which is synthesized manually and contains the CpG dinucleotide. By a receptor TLR9 activated immune system on immune cells, the adjuvant reinforces specific immune response aiming at vaccine antigens. The immunization effect of a vaccine can be increased by adding the vaccine adjuvant into the vaccine, so that the dosage of the vaccine antigen can be reduced and the vaccine cost can be reduced finally.

Aspects of the invention relate to immunostimulatory spherical nucleic acids (IS-SNA) for the treatment of a disorder, such as cancer. The IS-SNA may be administered together with a checkpoint inhibitor.

The present invention derives from the finding that increased levels of Toll related receptor 9 (TLR9) and Toll related receptor 7 (TLR7) are associated with liver cancer and in particular hepatocellular carcinoma. Accordingly, the invention provides TLR9 and TLR7 antagonists for use in a method of treating liver cancer. The invention provides other strategies such as modulation of endosomal signalling by using compounds such as chloroquine to prevent or treat such liver cancer. The invention also provides agents capable of inducing an immune response against TLR9 and TLR7 for use in a method of treating liver cancer. The presence of TLR9 and TLR7 expression may be indicative of the presence of liver cancer and the amount of TLR9 and TLR7 expression may be indicative of the rate of growth or spreading of the cancer.