29 results about "TLR3" patented technology

What is described is a peptide for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy. Furthermore, such a peptide is described for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy, wherein the immunostimulatory reactions / effects are induced by activation of IFIT1 / 2, IRF9, TLR3, TLR7, TLR8 or PKR.

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.

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.

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.

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.

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.

The invention belongs to the field of immunology and vaccinology, and particularly relates to a nucleic acid vaccine adjuvant based on tRNALeu and / or tRNAGln as well as a preparation method and application of the nucleic acid vaccine adjuvant. The nucleic acid vaccine adjuvant contains a recombinant sequence tRNALeu-SA of a chimeric nucleic acid aptamer, wherein the recombinant sequence tRNALeu-SA takes human active tRNALeu as a bracket; and / or a recombinant sequence tRNAGln-SA of the nucleic acid aptamer, which takes human-derived active tRNAGln as a bracket, is embedded into the human-derived active tRNAGln; the sequence of the human-derived active tRNALeu is a sequence with the similarity of more than 90% with SEQ ID NO.1; the sequence of the human-derived active tRNAGln is a sequence of which the similarity with SEQ ID NO.2 reaches 90% or above. The nucleic acid vaccine adjuvant obtained by the preparation method has low toxicity and low immunogenicity, can activate TLR3 and induce high-level antibody and cellular immune response, and significantly improves the immune effect of vaccines.

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.

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 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.

The invention provides a polymer composite adjuvant for an animal vaccine and a preparation method thereof, and the polymer composite adjuvant for the animal vaccine comprises acrylate hydrogel, nano oil emulsion and an immunopotentiator, the acrylate hydrogel is prepared by the following steps: generating a polyacrylate precipitate from an acrylic hydrophilic monomer and an acrylic hydrophobic monomer in a solvent by adopting a precipitation polymerization method, and immersing the precipitate in ultrapure water, the hydrophilic monomer is one of acrylic acid and methacrylic acid, and the hydrophobic monomer is acrylate with the carbon chain length of 10-22; the immunopotentiator is a TLR3 (toll-like receptor 3) or TLR9 (toll-like The polymer composite adjuvant disclosed by the invention has good biocompatibility, low mineral oil content and small side effects, not only can play an antigen slow release role, but also can improve the cellular immune response of an organism, has the average particle size of 40-60 nm, and is good in dispersity, and a prepared vaccine is low in viscosity and easy to inject; and the preparation process is simple, the stability is high, and the biological safety is good.

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.

Loss of B cell tolerance and generation of autoreactive anti-nuclear antibodies are hallmarks of systemic lupus erythematosus (SLE) and lupus nephritis. Lupus nephritis is characterized by glomerular and tubulointerstitial inflammation often initiated by the renal glomerular deposition of anti-nuclear immune complexes which trigger subsequent activation of complement, macrophages / monocytes and other innate inflammatory cells. The mechanism of anti-nuclear immunoglobulin accumulation and clearance in lupus nephritis pathogenesis remains largely uncharacterized. Here, we show that innate immune activation in the NZB / W F1 mouse model and in human lupus nephritis biopsies rapidly reduces DNase1 expression in renal cortex proximal tubular cells. To overcome the loss of endogenous DNase1, we treated lupus-prone mice with a hyperactive actin resistant variant of DNase1 with improved catalytic activity against nucleic acid-IgG immune complexes and acceptable in vivo pharmacokinetics. Hyperactive DNase1-Fc fusion protein ameliorates nephritis in a murine model of lupus nephritis and reduces immune complex deposition / complement fixation. Taken together, our data suggest that the loss of renal DNase1 through TLR signaling or other innate immune activation impairs clearance of autoreactive anti-nuclear immune complex deposits in the kidney to promote nephritis progression. Our findings provide a therapeutic rationale for using an engineered DNase1-Fc as a potential therapeutic approach in lupus nephritis.

According to the improved poly-ICLC compound provided by the invention, epsilon-polylysine is adopted to replace traditional poly-L-lysine, so that the cytotoxicity is remarkably reduced (ALT is reduced by 48.5%), and meanwhile, the excellent immune activation capability is kept (the tumor inhibition rate is increased by 9.5%). The compound can be stably preserved for more than 6 months at 4 DEG C, and is a safe and efficient cancer vaccine adjuvant.

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.

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 invention belongs to the technical field of biological medicines, and particularly relates to a porcine reproductive and respiratory syndrome nucleic acid vaccine adjuvant for activating Toll-like receptor3 as well as a preparation method and application of the porcine reproductive and respiratory syndrome nucleic acid vaccine adjuvant. The nucleic acid vaccine adjuvant for the porcine reproductive and respiratory syndrome contains a recombinant sequence which takes human serine tRNA as a bracket and is embedded with a conserved sequence of 3 'UTR in a PRRSV (Porcine Reproductive and Respiratory Syndrome Virus) genome. The conserved sequence of the 3 'UTR in the chimeric PRRSV genome is a sequence with the similarity of more than 90% with SEQ ID NO.1, and the recombinant sequence of the 3' UTR in the chimeric PRRSV genome is a sequence with the similarity of more than 70% with SEQ ID NO.2. The nucleic acid vaccine adjuvant produced by the invention has low toxicity and low immunogenicity, and can activate TLR3 and induce high-level antibody and cellular immune response.

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.

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 herein are compositions and methods for inhibiting the growth of a mammalian cancer cell growth or stimulating the immune response of a mammal, by contacting the cell or administering to the mammal an effective amount of a viral nanoparticle comprising at least one TLR agonist and a chemotherapeutic agent.

Embodiments of the present disclosure generally relate to compositions and methods for treating musculoskeletal disorders or conditions, such as osteoarthritis (OA). Specifically, the compositions and methods include activating mesenchymal stromal cell (MSC) with a stimulator of interferon gene (STING) agonist or a toll like receptor (TLR) agonist. A method of treating a musculoskeletal disorder or condition in a subject is disclosed. The method includes administering to the subject a composition including a MSC. The MSC include an activated signaling pathway downstream of (i) STING and / or (ii) TLR3. In another embodiment, a composition for treating musculoskeletal disorders or conditions in a patient is disclosed. The composition includes a MSC with pattern recognition receptors (PRR), wherein the PRR comprises an activated STING pathway, an activated a TLR3 pathway, or a combination thereof.

The invention discloses a culture medium for delaying senescence of mesenchymal stem cells and improving an immunosuppression function and a culture method, and belongs to the technical field of stem cell culture. The culture medium comprises the following components: a TLR3 agonist, a TGF beta agonist and VD. In order to solve the problems of function decline, immune regulation ability decline, insufficient dryness maintenance and the like in the existing mesenchymal stem cell (MSC) in-vitro amplification process, the mesenchymal stem cells are subjected to in-vitro culture in a culture medium containing a TLR3 agonist, a TGF beta agonist and VD, so that the aging of the mesenchymal stem cells can be delayed, and the immunosuppression function can be improved. An effective optimization strategy is provided for amplification and culture of the MSC before clinical application, the aging phenomenon of the MSC in the in-vitro culture process is delayed, meanwhile, the immunosuppression effect of the MSC is maintained, the multiplication capacity of the MSC is not affected, and the method has remarkable scientific research value and application prospects.

The application belongs to the technical field of biological medicine, and particularly relates to a porcine reproductive and respiratory syndrome nucleic acid vaccine adjuvant for activating Toll-like receptor 3, and a preparation method and application thereof. The porcine reproductive and respiratory syndrome nucleic acid vaccine adjuvant contains a recombinant sequence of a chimeric conservative sequence of 3'UTR in a PRRSV genome, which is taken as a scaffold of human serine tRNA. The chimeric conservative sequence of 3'UTR in the PRRSV genome is a sequence with a similarity of more than 90% to SEQ ID NO. 1, and the recombinant sequence is a sequence with a similarity of more than 70% to SEQ ID NO. 2. The nucleic acid vaccine adjuvant produced by the application has low toxicity and low immunogenicity, can activate TLR3, and can induce high-level antibody and cellular immune responses.

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.