156 results about "TLR7" patented technology

This invention relates to methods for treating or preventing hepatitis C virus infections in mammals using Toll-Like Receptor (TLR)7 ligands and prodrugs thereof. More particularly, this invention relates to methods of orally administering a therapeutically effective amount of one or more prodrugs of TLR7 ligands for the treatment or prevention of hepatitis C viral infection. Oral administration of these TLR7 immunomodulating ligands and prodrugs thereof to a mammal provides therapeutically effective amounts and reduced undesirable side effects.

The invention relates to the therapeutic use of novel stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides novel RNA-based oligoribonucleotides with improved nuclease and RNase stability and that selectively induce immune modulatory activity through TLR7.

The present invention provides methods of modulating the activation of certain Toll-like receptors (TLRs) such as TLR7 / 8 using chemically modified nucleic acid molecules. The present invention also provides methods of using such modified nucleic acid molecules to treat diseases or disorders associated with TLR7 / 8 activation such as systemic lupus erythematosus. The present invention further provides compositions comprising a combination of modified nucleic acid molecules and nucleic acid molecules that silence expression of one or more target sequences. Methods of using such compositions to reduce or abolish target gene expression without inducing cytokine production are also provided.

The invention provides a method for the treatment of superficial bladder cancer and inflammatory diseases of the bladder which employs certain Toll-like Receptor (TLR)-agonists.

The invention relates to an antigen and TLR agonist targeting co-loaded cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant, and a preparation method and an application thereof. A hydrophobic inner core is encapsulated with a TLR7 agonist, a phospholipid layer is encapsulated with a TLR4 agonist, an antigen is adsorbed by cationic phospholipids in the phospholipid layer, and ligation of a mannose ligand makes the vaccine adjuvant like a specific targeting antigen to have the dendritic cell presenting ability, so the DC cell intake and the maturation promoting effect are enhanced; and the antigen is protected by hybridized nanoparticles, the antigen uptake by DC cells is improved, immune response after antigen stimulation is significantly enhanced by the TLR agonist, and thecross-presentation of the antigen is significantly improved, so vaccine adjuvant has a strong potent T cell killing effect, can induce cytokine secretion, has a long-acting memory T cell response, andhas an excellent prevention effect on tumors.

The invention relates to condensed ring based ketone derivatives, a preparation method thereof and an application of the derivatives in medicine, in particular to the new condensed ring based ketone derivatives shown as the general formula (I) in the description, the preparation method of the derivatives, pharmaceutical composition containing the derivatives and the application of the derivative as a therapeutic agent, especially a TLR7 (toll-like receptor 7) agonist. Substituent groups in the general formula (I) are defined as the description.

The invention relates to a cationic phospholipid-polymer hybridized nanoparticle vaccine adjuvant of a common-carrier antigen, MPLA (Monophosphoryl Lipid A) and IMQ (Imiquimod) as well as a preparation method and application thereof. The vaccine adjuvant is characterized in that the IMQ as a TLR7 agonist is loaded on a hydrophobic core; the MPLA as a TLR4 agonist is loaded in a phopholipid layer;cationic phospholipid DOTAP (1,2-dioleoy-3-trimethylammonium-propane) in the phopholipid layer is used for adsorbing an antigen; the antigen is protected through hybridized nanoparticles, and the ingestion of the antigen by dendritic cells is improved; immune response after antigen stimulation is improved remarkably through the TLR agonist, and cross-presentation of the antigen is improved remarkably. The hybridized nanoparticles as the vaccine adjuvant can load the antigen and different types of TLR agonists simultaneously, can deliver the antigen through a plurality of immune paths, and promotes the DC activation and maturation. The cross-presentation level is raised, a strong and powerful T-cell killing effect is achieved, cell factor secretion is induced, a long-term memory T-cell reaction is generated, and higher prevention capability for tumors is achieved.

The invention relates to a method for culturing gamma-delta-T cells, and more specifically relates to a method for in-vitro amplification of gamma-delta-T cells. The method comprises the following operating steps: pre-coating a T75 culture bottle with a TCR-gamma-delta resisting antibody and CD28McAb for later use; isolating peripheral blood mononuclear cells (PBMC) of patients; regulating PBMC concentration to 1*10<6> / ml with a serum-free culture medium which contains 5% of autologous plasma, and transferring the PBMC cell suspension into the T75 culture bottle; adding an initial culture medium which contains proper concentrations of Zoledronat, HSP70, Toll-like Receptors7 (TLR7) ligand, Levamisole (LMS), IL-2, IL-7 and IL-15; culturing in a saturated humid environment containing 5% of CO2 at 37 DEG C; according to growth situation of the cell, changing the culture medium every 2 to 3 days so as to control the cell concentration at about 2.5*10<6> / ml; meanwhile, compensating full doses of Zoledronat, HSP70, Toll-like Receptors7 (TLR7) ligand, Levamisole (LMS), IL-2, IL-7 and IL-15;; and continuously culturing for 12to 16 days so as to obtain a great amount of gamma-delta-T cells which are comparatively high in purity.

The invention relates to a DCs vaccine based on phospholipid hybrid polymersome jointly encapsulating an antigen and dual immunoagonists, a preparation method and application thereof. The phospholipidhybrid polymersome which can jointly load a model antigen OVA and two types of TLR agonists (TLR7 / 8 and TLR4) is used for stimulation in vitro of the DCs so as to realize the effective phagocytosis of DCs cells. The rapid and long-term immunostimulatory effect on the DCs is achieved by the internal and external co-loading of the OVA antigen. The synergistic effect of the two types of TLR agonistssignificantly enhances the immune response after antigen stimulation; the phospholipid hybrid polymersome which jointly encapsulates the antigen and the dual immunoagonists can effectively promote the activation and maturation of the DCs, increases the level of cross-presentation, promotes the migration of the DC vaccine to secondary lymphoid organs, and produces a strong specific cytotoxic T lymphocytes (CTLs) killing effect, thereby effectively killing tumor cells and realizing the immunotherapy of the DCs vaccine on tumors.

The present invention is directed to compositions and methods for treating hepatitis B virus infection. In particular, the present invention is directed to a combination therapy comprising administration of a TLR7 agonist and an HBV capsid assembly inhibitor for use in the treatment of chronic hepatitis B patient.

We formulated multiple TLR agonists into GVAX (lethally irradiated tumor cell vaccines engineered to secrete GM-CSF). Specifically, GLA and R848, TLR4 and TLR7 / 8 agonists found to be safe in patients, were formulated with GVAX (TEGVAX—for TLR agonists enhanced GVAX), and this formulation was effective in producing anti-tumor responses in 3 different preclinical models, including palpable B16. These anti-tumor responses were correlated with increased CD4 and CD8 T-cells that can secrete IFNγ circulating in the tumor microenvironment as well as significantly higher level of p15E specific CTL mediated cell killing in mice treated with TEGVAX in comparison to controls. When combined with anti-PD-1 antibody, TEGVAX was able to induce regression of established B16 tumors.

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.

This invention relates to methods for treating or preventing hepatitis C virus infections in mammals using Toll-Like Receptor (TLR)7 ligands and prodrugs thereof. More particularly, this invention relates to methods of orally administering a therapeutically effective amount of one or more prodrugs of TLR7 ligands for the treatment or prevention of hepatitis C viral infection. Oral administration of these TLR7 immunomodulating ligands and prodrugs thereof to a mammal provides therapeutically effective amounts and reduced undesirable side effects.

The efficacy of rabies vaccines can be enhanced by adjuvanting rabies virus immunogens with a mixture of a TLR agonist (preferably a TLR7 agonist) and an insoluble metal salt (preferably an aluminium salt). The TLR agonist is typically adsorbed to the metal salt. The rabies virus immunogen can also be adsorbed to the metal salt.

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 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 invention discloses sheep X and Y sperm sorting liquid, a sorting floating system and a sorting method. According to the disclosed scheme, sheep sperms X and Y are sorted by using a specific protein TLR7 / 8 agonist R848 "floating system". According to the technology for activating and sorting the X and Y sperms through the specific protein TLR7 / 8 of the X and Y sperms of the milk goat, the separation method is simple, the effect is good and reliable, and the X and Y sperms of the milk goat can be efficiently separated; the X sperms sorted by the method are used for in-vitro fertilization, and the proportion of female embryos reaches 80.52%; the X sperms sorted by the method are used for artificial insemination, and the proportion of female embryos reaches 88.89%.