306 results about "Toll-like receptor" patented technology

Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.

This invention discloses immunostimulatory combinations of Tumor Necrosis Factor Receptor Superfamily (TN-FRSF) agonists, Toll-Like Receptor (TLR) agonists, “domain present in NAIP, CIITA, HET-E, TP-I (NACHT)-Leucine Rich Repeat (LRR)” or “NLR” agonists, RIG-I-Like Helicase or “RLH” agonists, purinergic receptor agonists and cytokine / chemokine receptor agonists, together with delivery methods. The combinations, when used alone at the site of pathology, provide immunostimulation that induces host humoral and cellular immunologic responses to eliminate pathogens or neoplasms. Alternatively, when the combinations are used with a defined antigens, these combinations can induce focused humoral and cellular immunologic responses useful as prophylactic and / or ameliorative therapeutic modalities for infections and the treatment of neoplastic disorders.

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.

Mammals are treated with agonists of bacterially-activated TLRs. The agonist are administered orally or mucosally. In one embodiment, the mammal treated is subject to a gastro-intestinal injury. The agonist can be administered prior to infliction of the gastro-intestinal injury, subsequent to infliction of the gastro-intestinal injury and concurrently with infliction of the gastro-intestinal injury. In another embodiment, the mammal is subject to tissue damage. The agonist is administered prior to the primary treatment, following the primary treatment or concurrently with the primary treatment.

Compositions comprise a flagellin component or a Toll-like Receptor agonist component that is at least a portion of a flagellin or a Toll-like Receptor agonist, wherein the flagellin component or Toll-like Receptor agonist component includes at least one cysteine residue and whereby the flagellin component or Toll-like Receptor agonist component activates a Toll-like Receptor 5 or Toll-like Receptor. Compositions comprise a flagellin component that is at least a portion of a flagellin, wherein at least one lysine of the flagellin component has been substituted with at least one arginine, serine and histidine, whereby the flagellin component activates Toll-like Receptor 5. Compositions can further include an antigen, such as an influenza antigen, a flavivirus antigen, a pathogen-related antigen, a bacterial capsular antigen and a carrier protein. The compositions are used to stimulate an immune response and a protective immune response in a subject.

The present invention is related to the fields of vaccinology, immunology and medicine. The invention provides compositions and methods for enhancing immunological responses against antigens coupled or fused to virus-like particles (VLPs) packaged with immunostimulatory nucleic acids, preferably oligonucleotides containing at least one non-methylated CpG sequence and a toll-like receptor (TLR) ligand. The invention can be used to induce strong antibody and T cell responses particularly useful for the treatment of allergies, tumors and chronic viral diseases as well as other chronic diseases.

The present invention relates to the use of a TLR9 agonist and / or a TLR4 antagonist and / or a NOD2 agonist for treatment or prevention of disorders involving TLR4 activation, such as systemic sepsis and necrotizing enterocolitis.

The invention provides methods of reducing the severity of mucositis, involving administration of a toll-like receptor 4 antagonist.

Disclosed herein are methods of producing conjugates that include Toll-like receptor (TLR) ligands and targeting molecules that are effective in inducing an immune response. Also disclosed are methods of using such conjugate to treat a disease, such as cancer, infectious diseases and autoimmune diseases.

The present invention relates to compounds and methods useful in the prevention or treatment of diseases or conditions associated with Toll-like receptor 2 activation.

Small molecule compounds and compositions containing said compounds useful for inhibiting signaling by certain Toll-like receptors (TLRs), particularly TLR9, are provided. The compounds and compositions can be used to inhibit immune responses, including unwanted immune responses in particular. Compounds, compositions, and methods are provided to treat a variety of conditions involving unwanted immune responses, including for example autoimmune disease, inflammation, transplant rejection, and sepsis.

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.

Embodiments of the disclosure relate to selectively substituted quinoline compounds that act as antagonists or inhibitors for Toll-like receptors 7 and / or 8, and their use in pharmaceutical compositions effective for treatment of systemic lupus erythematosus (SLE) and lupus nephritis.

The present invention provides a monoclonal antibody which specifically binds to human Toll-like receptor 3. Further, the present invention provides an inhibitor which (a) suppresses a double-stranded RNA-mediated immune response in a cell which expresses Toll-like receptor recognizing the double-stranded RNA and produces type I interferon, and (b) includes an antibody, which binds to the Toll-like receptor and inhibits production of the type I interferon. Particularly, the antibody is a monoclonal antibody against human Toll-like receptor 3. Further, the present invention provides a transfection method comprising the step of infecting a cell which expresses Toll-like receptor recognizing a double-stranded RNA and produces type I interferon by expressing Toll-like receptor recognizing a double-stranded RNA with a recombined virus vector, in which a gene of interest has been inserted, under the inhibitory condition for production of the type I interferon by using an inhibitor including an antibody which binds to the Toll-like receptor. Thus, it is possible to provide (i) an inhibitor which inhibits the production of the type I interferon induced by a virus double-stranded RNA so as to suppress an immune response against the virus, and (ii) a transfection method or a transfection kit whereby a transfection efficiency is improved without enhancing an infectious capacity of a virus vector.

The present invention relates to bispecific molecules that are characterized by having a first binding domain which binds an antigen present in the circulation of a mammal and a second binding domain which binds the C3b-like receptor (known as complement receptor 1 (CR1) or CD35 in primates). The bispecific molecules do not consist of a first monoclonal antibody to CR1 that has been chemically cross-linked to a second monoclonal antibody. The invention also relates to methods of making the bispecific molecules and therapeutic uses thereof, as well as to kits containing the bispecific molecules. The invention further provides polyclonal populations of bispecific molecules, which comprise populations of bispecific molecules with different antigen recognition specificities. Such polyclonal populations of bispecific molecules can be used for targeting multiple epitopes of a pathogenic antigenic molecule and / or multiple variants of a pathogenic antigenic molecule.

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.

Dendritic cells (DC) play a critical role in antigen-specific immune responses. Materials and Methods are provided for treating disease states, including cancer, by activating dendritic cells from the host which are rendered hypo-responsive to activation stimuli by the disease. In particular, methods are provided for treating cancer in a mammal comprising administering to said mammal an effective amount of a tumor-derived DC inhibitory factor antagonist in combination with an effective amount of a Toll-like receptor (TLR) agonist.

The present invention provides compositions and methods for generating and cryopreserving dendritic cells with superior functionality in producing stronger signals to T cells, resulting in a more potent DC-based anti-tumor vaccine. The present invention includes mature, antigen loaded DCs activated by Toll-like receptor agonists that induce clinically effective immune responses, preferably when used earlier in the disease process. The DCs of the present invention produce desirable levels of cytokines and chemokines, and further have the capacity to induce apoptosis of tumor cells. The cells can be cryopreserved and thawed for later use, thereby reducing the need for repeated pheresis and elutriation processes during vaccine production. These methods can also be utilized to directly target molecules involved in carcinogenetic signaling pathways and cancer stem cells.

The invention is directed to methods and compositions for enhancing immunity, including mucosal immunity. The compositions include an antigen or immunogen, a ligand for a Toll-like receptor and at least one chemoattractant.

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 provides novel oligonucleotide-based TLR antagonists containing a modified immune stimulatory motif and the use of such compounds in the prevention and treatment of TLR-medicated diseases. These oligonucleotide-based TLR antagonists containing a modified immune stimulatory motif have one or more chemical modifications in the immune stimulatory motif, which would be immune stimulatory but for the modification.

Compositions that include Toll-like Receptor 5 agonists and at least a portion of at least one viral antigen can be employed in methods that stimulate an immune response in a subject, in particular, a protective immune response in a subject. Compositions can be associated with particles and employed in the methods in relatively low doses to provide protective immunity to viral infection.

The invention provides immunostimulatory compositions and methods for their use. In particular, the immunostimulatory compositions of the invention include RNA-like polymers that incorporate an immunostimulatory sequence motif and at least one chemical modification to confer improved stability against nuclease degradation and improved activity. Specific modifications involving phosphate linkages, nucleotide analogs, and combinations thereof are provided. Compositions of the invention optionally include an antigen and can be used to stimulate an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an to allergic condition, or asthma. Modified oligoribonucleotide analogs of the invention are believed to stimulate Toll-like receptors TLR7 and TLR8.