12 results about "TLR3" patented technology

The application discloses a kind of nanoparticles for tumor sonodynamic combined individualized immunotherapy and its preparation method and application, belong to the field of biological medicine.The nanoparticles for tumor sonodynamic combined individualized immunotherapy are double-shell core structure nanoparticles formed by inner core and shell, and the inner core is formed by self-assembly of TLR3 agonist Poly (I:C), L-arginine and polylysine, and the shell is hyaluronic acid layer HA-Ce6 conjugated with photosensitizer Ce6.It is found through experiment verification that the nanoparticles can target tumor, generate reactive oxygen species to kill tumor cells under the action of ultrasound, promote M1 macrophage polarization and produce NO release at the same time, play the role of antitumor and immune effect, and realize the combined application of sonodynamic and NO gas therapy.The nanoparticles for tumor sonodynamic combined individualized immunotherapy can trigger systemic immune response, inhibit primary tumor, produce immune memory effect, and prevent tumor metastasis and recurrence.

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.

This invention provides a method for screening peptides that specifically target T cells, comprising providing T cells having a subset selected from CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L) The T cells are labeled with at least one of the following surface antigen markers: CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7. The T cells are then contacted with a peptide display library, and target peptides that specifically bind to the T cells are screened therefrom.

A multi-target DC vaccine based on tumor antigen epitope peptides and its application belong to the field of tumor immunotherapy technology. The vaccine comprises an hr-8 conjugate peptide, an immune adjuvant, a carrier, and an immune memory enhancer. The hr-8 conjugate peptide is a conjugate product formed by chemically linking an hr-8 targeting peptide with at least two different tumor antigen CTL epitope peptides. The immune adjuvant is a combined adjuvant system of the TLR9 agonist CpG ODN and the TLR3 agonist poly(I:C). The carrier is PLGA nanoparticles, and the immune memory enhancer is IL-7 and / or IL-15. This invention utilizes the specific binding of the hr-8 peptide to the DEC-205 receptor on the surface of dendritic cells to achieve efficient synergistic delivery and cross-presentation of multi-target antigens. The combined adjuvant and memory factor significantly enhance CTL activation and promote long-term immune memory formation, giving the multi-target DC vaccine advantages such as strong targeting, broad antigen coverage, and prolonged relapse-free survival.

Provided is a method for screening polypeptides that specifically target T cells, comprising: providing T cells having a surface antigen marker selected from at least one of CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L), CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7; and contacting the T cells with a polypeptide display library, and screening therefrom target polypeptides that specifically bind to the T cells.

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 invention relates to a method for treating cancers. Many cancers harbour sternness signature to de-differentiate into immature progenitors confer to tumor clones the re-expression of genes from fetal development. Inventors have obtained mice per group which received two boosts of vaccine 7 and 14 days with 2×106 irradiated hESCs cells that were mixed with 3 different adjuvants: 500 μg of TLR3, 50 μg of TLR9 agonist or 50 μg / ml of Quil A® Saponin vaccine adjuvant. After 14 days 5×104 4T1 cells were injected into the mammary fat pad of the mice and Valproic acid added in the drinking water at the dose of 4 mg / ml. They have shown that in contrast to the non-vaccinated mice, the mice vaccinated with hESC combined with a TLR3 agonist have generated the highest reduction of breast tumor volume (p<0.001) compared to the use of a TLR9 agonist or to Quil-A® Saponin vaccine adjuvant. Accordingly, the invention relates to a method for treating a subject suffering from a cancer with i) an agent that induces MHC-I presentation of antigens, ii) a vaccine composition containing an immunogenic element and iii) an adjuvant.

This invention provides a probe library and kit for detecting genetic risk gene mutations in viral infections, belonging to the field of gene detection technology. The probe library and kit designed in this invention achieve, for the first time, the simultaneous detection of all mutations in the following 51 genetic risk genes for viral infections: CARMIL2, CCL2, CD27, CD70, CIB1, CTPS1, CXCR4, CYBC1(C17orf62), DBR1, FCGR3A, FCHO1, ICAM1, IFIH1, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IL10, IL10RA, IL10RB, IL... The probe library and kit of this invention contain 18BP, IRF3, IRF7, IRF9, MAGT1, LIG1, MCM2, NOS2, OAS1, POLR3A, POLR3C, POLR3F, PRKCD, RASGRP1, SH2D1A, STAT1, STAT2, TBK1, TICAM1, TLR3, TLR7, TLR8, TMC6, TMC8, TNFRSF9, TRAF1, TRAF2, TRAF3, TYK2, UNC93B1, and XIAP. This invention's probe library and kit can be used for detecting genetic variations in the risk of viral infection in clinical settings, assessing an individual's genetic risk of viral infection, and has broad application prospects.

The present invention relates to an antagonistic small molecule compound having a function of inhibiting an endosome toll-like receptor (TLR), and more particularly to: a small molecule compound for inhibiting a TLR3 / 7 / 8 / 9 signaling pathway; a composition for inhibiting a toll-like receptor comprising the small molecule compound; and a composition for preventing or treating an autoimmune disease, an inflammatory disease, or a viral disease. The compound according to the present invention shows very significant results in a systemic lupus erythematosus animal model, which not only prevents TNF-α secretion induced by poly I:C (TLR3 agonist), imiquimod (TLR7 agonist), TL8-506 (TLR8 agonist), or ODN2395 (TLR9 agonist), but also inhibits the production of inflammatory cytokines. This indicates that the compound can also be used for preventing or treating TLR3, TLR7, TLR8, or TLR9-related autoimmune diseases, inflammatory diseases, and viral diseases.

The invention provides a nasal mucosa vaccine adjuvant, a nasal mucosa vaccine, a preparation method and application, and belongs to the technical field of vaccine adjuvants. The invention provides a virus bionic nasal mucosa vaccine adjuvant, which takes nanoparticles as a carrier, a nucleic acid-like TLR agonist is loaded in the virus bionic nasal mucosa vaccine adjuvant, and a polysaccharide adjuvant is modified on the outer surface of the virus bionic nasal mucosa vaccine adjuvant; raw materials for preparing the nanoparticles comprise an amphiphilic polymer material and cationic lipid. From the structure, a shell of a nanoparticle of the nasal mucosa vaccine adjuvant simulates a virus envelope, a nucleic acid-like TLR agonist simulates virus nucleic acid, and the outer surface of the nanoparticle is modified with a polysaccharide adjuvant simulative virus glycoprotein; from the perspective of functions, the nasal mucosa vaccine adjuvant reengraves a virus infection time sequence, firstly activates a TLR2 / 4 pathway through a polysaccharide adjuvant to start mucosa immunity, and then activates an intracellular TLR3 pathway through a nucleic acid-like TLR agonist, so that dual-pathway synergistic interaction is realized, and the problem that mucosa and system immunity are disjointed by a traditional adjuvant is solved.

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.

This invention relates to peptide ligands capable of binding to TLR3. Specifically, the invention describes bicyclic peptide ligands comprising the peptide ligand described herein and a molecular scaffold, wherein three cysteine ​​residues of the peptide ligand are covalently bonded to the molecular scaffold to form two circular sequences. The invention also includes pharmaceutical compositions, polymeric binding complexes, and pharmaceutical conjugates comprising the said peptide ligand, and the use of the said peptide ligand in the prevention, inhibition, or treatment of TLR3-mediated diseases or conditions, such as autoimmune diseases, inflammatory conditions, and cancer.