25 results about "Toll" patented technology

A Toll-like receptor (TLR) is an indispensable component of an innate immune system and plays a key role in identifying and coping with microbial pathogens. TLR7, TLR8, and TLR9 are located in the endosome-lysosome compartment within the cell and then exclusively used to detect nucleic acids of a microorganism after the microorganism is swallowed and reaches the endosome compartment. The biological importance of the TLR agonists lies in that they can be used as powerful tools for studying innate immune responses, developing vaccines and potential therapeutic applications. In addition, TLR agonists have been explored for use as immunotherapy, while these TLR antagonists can be used as new pathogenic nodes in the context of different autoimmune diseases. Therefore, the agonists and antagonists of the endosomal TLR have therapeutic significance in different clinical backgrounds. The previous study on 8-oxo adenines shows that the C-6-site-NH2 group is extremely important for the recognition of agonistic active sites and the subsequent induction of interferon (IFN). The present invention explores the ability of a hydrogen-substituted 8-oxopurine derivative that does not contain an essential C-6 amine group. The C-6 amino group in the 8-oxopurine derivative is substituted by hydrogen (H), providing an exciting opinion for regulating the endosome TLRs (Toll-Like Receptors). The ability of 8-oxopurine derivatives to modulate the endosomal TLR has been reported, which derivatives are related / interrelated to various substitutions at N-7, N-9 and C-2, all derivatives containing hydrogen at C-6. Structure 1

Provided is an adjuvant composition comprising a glycoarchaeol and at least one immunostimulant selected from a Toll-like receptor (TLR) agonist and a saponin. The glycoarchaeol and / or immunostimulant may be present as a pharmaceutically acceptable salt. The adjuvant composition may be comprised together with an antigen in an immunogenic composition, such as a vaccine composition, which may be for use to induce an immune response in a subject. Further provided is use of the immunogenic composition to induce an immune response in a subject, particularly an immune response that comprises both a cell-mediated response and a humoral response.

The present disclosure relates to the use of compound (I) and any of its salts for the treatment of a neoplasm characterized by high expression of toll-like receptor 4 (TLR4) in the tumor or its microenvironment, associated with at least one of the pathophysiological complications including immunosuppression, angiogenesis, fibrosis, or metastasis.

The invention belongs to the field of medicinal chemistry and pharmacology, and relates to application of a novel glycolipid TLR2 agonist 13-C in preparation of vaccine adjuvants and anti-tumor treatment. The compound is excellent in human TLR2 agonist activity, EC50 reaches 2.2 nM, and the compound is simple in structure, easy to prepare and excellent in solubility and has industrial application potential. In a B16-OVA tumor model, the antibody induction capacity of the compound is superior to that of a positive control drug Diprovocim, and the anti-tumor activity of the compound is more remarkable; in addition, PD-L1 expression of tumor tissue can be effectively down-regulated, and a synergistic anti-tumor effect is generated with a PD-L1 monoclonal antibody Atezolizumab. Besides, 13-C and a vaccine adjuvant QS-21 are combined for use, so that a synergistic enhancement effect is achieved, the antibody titer induced by a vaccine can be remarkably improved, antibody subtypes are enriched, meanwhile, cellular immunity and humoral immunity response of an organism are stimulated, and the effect of dual immune activation is achieved.

The application discloses a targeted acne-removing composition suitable for sensitive skin and a preparation method and application thereof. The targeted acne-removing composition comprises lysozyme, a first extract and a second extract in a mass ratio of 1:(0.1-10):(0.1-5). The first extract comprises guaiacum extract and myrtle fruit extract. The second extract comprises sophora flavescens extract and angelica sinensis extract. The targeted acne-removing composition containing lysozyme, the first extract and the second extract in specific mass ratios can inhibit the activity of propionibacterium acnes, down-regulate the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), and achieve efficient acne removal, and has the mild property and can be suitable for sensitive skin.

This application relates generally to toll like receptor modulator compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR8), and methods of making and using them.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid (RP) and one or more sequences of micro-interfering ribonucleic acid (miRNA). When the RP interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a toll-like receptor. In some embodiments of the present disclosure, the toll-like receptor is TLR3.

The invention discloses Toll gene dsRNA and application thereof in improving the effect of abamectin in preventing and treating diaphorina citri. The invention provides a technical scheme for preventing and treating diaphorina citri through combined use of dsRNA of a targeted DcToll gene and abamectin, specifically, the DcToll gene of the diaphorina citri is silenced, the immune response of the diaphorina citri is inhibited, and the potential tolerance of the diaphorina citri to abamectin can be reduced. The method provided by the invention is expected to realize the synergistic interaction of immunosuppression and chemical agents, provides a new technical thought for improving the control effect of abamectin and delaying the development of resistance, and is beneficial to the realization of pesticide reduction and synergism.

The invention provides a high-sensitivity in-vitro pyrogen detection method, which is characterized in that on the basis of an in-vitro pyrogen detection method (reporter gene method), a transgenic cell which expresses a Toll-like receptor and transfects an NF-kB reaction element and a luciferase gene is used for detecting a pyrogen, the pyrogen is combined with the Toll-like receptor on the surface of the cell to activate an NF-kB signal channel, and the NF-kB reaction element and the luciferase gene are converted into the NF-kB signal channel. Therefore, the expression of luciferase is activated.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

Methods of modulating an immune response for the treatment of cancer includes compositions which comprise chimeric molecules with an anti-CD47 binding domain and an immunomodulatory agent.

The present invention relates generally to the field of immunomodulation and more specifically to compounds that exhibit Toll-like receptor 4 (TLR4) agonist activity. The invention provides novel compounds capable of stimulating or promoting an immune response, thereby offering potential therapeutic applications. In particular, the compounds may be useful in methods of promoting and / or maintain gastrointestinal health, as well as treating or preventing gastrointestinal diseases, such as IBD and colitis.

Compounds can specifically activate TLR7. The compounds are useful because they can stimulate innate immunity. The compounds can be used in the treatment of conditions including cancer, viral infections and skin lesions. The compounds can optionally be formulated for enhanced penetration following topical administration, the composition preferably initiating a local specific inflammatory cytokine response while limiting undesirable erythema and other inflammatory reactions. Pharmaceutical compositions contain the compound and preferably an additional compound such as imiquimod and / or resiquimod (R848). A composition contains the compound and a compound can be used as a medicament. Other aspects, embodiments, advantages and applications will become clear from the further description herein.

The invention relates to the technical field of allergen detection, and particularly discloses a food allergen detection kit based on TLR4 and ZO-1. The kit comprises a TLR4 detection reagent, a ZO-1 detection reagent, a creatinine detection reagent and a protease inhibitor and is used for jointly detecting the concentration of a Toll-like receptor (TLR4) and the concentration of tight junction protein (ZO-1) in urine, and the concentration is compared with a preset threshold value after standardization of urine creatinine so as to realize noninvasive and early diagnosis of food allergy. According to the invention, TLR4 and ZO-1 are integrated in the kit as combined biomarkers for the first time, and the kit is especially suitable for infant population, has the advantages of safety, convenience, high sensitivity, strong specificity and the like, and can be used for screening and auxiliary diagnosis of allergy of various foods such as milk, eggs, peanuts, seafood and the like.

This invention provides vaccine adjuvant lipid compounds based on Toll-like receptor agonists and their uses. [Solution] Specifically, the present invention discloses a compound represented by formula (I), its stereoisomer, its N-oxide compound, its solvate, or a pharmaceutically acceptable salt thereof. The mRNA-TLP composition produced with the adjuvant lipid compound of the present invention can significantly improve the targeting of mouse spleen antigen-presenting cells and significantly inhibit tumor growth. TIFF2026109612000078.tif38170

An immuno-nanoparticle construct for use in therapeutic applications includes a nanocarrier, a stimulator of interferon (IFN) genes (STING) pathway agonist, and a toll-like receptor 4 (TLR4) agonist, wherein the STING pathway agonist and the TLR4 agonist are co-loaded in the nanoparticle carrier.

The present invention discloses a Toll-like receptor agonist-based vaccine adjuvant lipid compound and use thereof, and specifically discloses a compound of formula (I), or a stereoisomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof. The mRNA-TLP composition prepared from the adjuvant lipid compound of the present disclosure significantly enhances targeting to antigen-presenting cells in mouse spleen and can significantly inhibit tumor growth.

Provided herein are novel synthetic pathway activators comprising transmembrane domains and tiled intracellular signaling domains comprising a combinatorial signaling domain comprising two or more Signal Transducer and Activator of Transcription (STAT)1, STAT3, STAT4, STAT5 and / or Toll-like receptor (TLR) / IL-1R (TIR) signaling domains(s).

Toll-like receptors (TLRs) are integral components of the innate immune system, serving as key players in the recognition and response to microbial pathogens. TLR7, TLR8 and TLR9 are located inside the cell within the endosomal-lysosomal compartments, subsequently specialized for detecting microbial nucleic acids after microbes get phagocytosed and reach the endosomal compartments. The biological importance of TLR agonists lies in their ability to serve as powerful tools for studying innate immune responses, developing vaccines, and potential therapeutic applications. Additionally, TLR agonists have been explored as immunotherapies, whereas antagonists of these TLRs could serve as novel pathogenic node in different autoimmune disease contexts. Thus, both agonists and antagonists of these endosomal TLRs have therapeutic significance in different clinical context. The previous studies in 8-oxoadenine class depicted that the C-6 position -NH2 group is extremely important for recognition of the agonistic active site and subsequent interferon (IFN) induction. The present invention explores ability of 8-oxopurine derivatives, which does not contain the essential C-6 amine group and was replaced with hydrogen. The replacement of C-6 amino with a hydrogen (H) in 8-oxopurine derivatives provided exciting insight into these endosomal TLR modulation. The ability to modulate the endosomal TLRs by 8- oxopurine derivatives in correlation / interrelation with various substitution at N-7, N-9 and C-2 with all the derivatives containing hydrogen at C-6 were reported.

The present disclosure relates to lipid-like compounds comprising toll-like receptor (TLR) agonists, lipid nanoparticles (LNP) comprising the same, and methods of use thereof. In certain embodiments, the LNPs described herein can be used to enhance the therapeutic and / or prophylactic effect of a vaccine composition.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

Provided is a drug combination of a Toll-like receptor 7 agonist and an anti-PD-L1 antibody. In particular, provided are a drug combination of a compound, which is represented by formula I and which acts as a TLR7 agonist, and an anti-PD-L1 antibody, and a medical use thereof.