195 results about "TLR4" patented technology

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 a construction method of a cell model for detecting pyrogens, the cell model and a pyrogen detection kit. The cell model utilizes specific locations of CRISPR / CAS9 induced genomes to form double-bond fission, TLR4 and CD14-MD2 are knocked into two chromosomes of a cell line respectively by the aid of the homologous recombination repair principle, green fluorescence GFP and red fluorescence RFP are respectively used for tracing finally successfully constructed TLR4 / CD14 / MD2 fixed-point knocked-in fluorescent tracer cell models, and the LPS stimulating cell model can detect release of IL-6 and TNF-a cytokines by means of ELISA, Western Blot, mass spectrum and immunomagnetic beads. The cell model is good in stability and high in sensitivity, and the lowest detectable limit can reach 0.005EU / mL and is far lower than 0.025EU / mL of the Tachypleus Amebocyte Lysate method.

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.

With the current invention, we provide new methods of enhancing the T-cell stimulatory capacity of human dendritic cells (DCs) and their use in cancer vaccination. The method comprises the introduction of different molecular adjuvants to human DCs through transfection with at least two mRNA or DNA molecules encoding markers selected from the group of: CD40L, CD70, constitutively active TLR4 (caTLR4), IL-12p70, EL-selectin, CCR7 and / or 4-1 BBL; or in combination with inhibition of SOCS, A20, PD-L1 and / or STAT3 expression, for example through siRNA transfection. We could show a clear increase in the immunostimulatory capacity of DCs obtained in this way, enabling them to elicit an unexpectedly high T-cell immune response in vitro. Introduction of at least two of the above molecules, in combination with a tumor-specific antigen enables the DCs to elicit a significant host-mediated T-cell immune response in vivo against the tumor antigen and thus makes them very attractive in the manufacturing of anti-cancer vaccines.

An assay for Alzheimer's disease (AD) pathology in a living patient is disclosed wherein an amount of α7nAChR or TLR4 in a FLNA-captured protein complex or α7nAChR in an Aβ-captured protein complex or α7nAChR-FLNA, or TLR4-FLNA and / or α7nAChR-Aβ42 complex present as a protein-protein complex in a sample is compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is compared to an amount in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four pharmacophores of FIGS. 7-12. An amount of protein or protein complex determined in the presence of medicament that is less than the first amount indicates a favorable treatment prognosis.

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.

Antisense oligonucleotide compounds, compositions and methods for downregulating TLR4 expression are provided. The composition comprises an antisense oligonucleotide targeted to a nucleic acid encoding TLR4. The composition may also comprise an antisense oligonucleotide targeted to a TLR4-encoding nucleic acid in combination with other therapeutic and / or prophylactic compounds and / or compositions. Methods of using these compounds and compositions to downregulate TLR4 expression and prevent or treat diseases that would benefit from modulating TLR4 expression are provided.