183 results about "Immune activation" patented technology

The invention relates to an immune sensitization IRE treatment platform based on NK cell membrane coated manganese carbonate. A manganese carbonate composite nano material is formed by coating the surfaces of manganese carbonate nano particles with cell membranes. According to the invention, higher tumor specificity enrichment is realized, non-target tissue accumulation and systemic toxicity risks are reduced, collaborative integration of tumor targeted delivery, immune activation and IRE ablation is realized, and compared with single IRE, anti-tumor immune response is significantly enhanced.

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The application discloses a method for preparing cell-derived exosomes and products and applications thereof, and the method comprises the following steps: co-culturing immune-activated programmable cells with a stimulating agent with immune-activation effect, and collecting the cell-derived exosomes with immune activity by a natural secretion collection method or an artificial extrusion collection method. The application has safe and controllable local immune activation, and the immune activation strategy based on the exosomes fully overcomes the safety bottleneck of traditional live bacterial preparations in tumor treatment. By replacing live bacteria with engineered exosomes, not only potential risks such as systemic inflammatory response and infection are effectively avoided, but also the local controllability of immune stimulation signals is ensured, the precise activation and directional regulation of tumor region immune cells are realized, the tumor microenvironment is reshaped, the anti-tumor effect is strengthened, and the broad-spectrum cross-tumor potential is verified across models.

The invention provides an allosteric nanogel adjuvant as well as a preparation method and application thereof, and belongs to the technical field of vaccines. The allosteric nanogel adjuvant comprises a self-assembly motif, a responsive site and an immunomodulatory peptide fragment, and the self-assembly motif is composed of 2-5 amino acids; the allosteric nanogel adjuvant has a structure as shown in a formula I, and is named as NTP5 for short; the allosteric nanogel adjuvant is self-assembled into nanoparticles, the nanoparticles are allosteric into a nanofiber structure through responsive broken bonds, nanogel is further formed, and the key problems of a traditional vaccine in the aspects of antigen delivery and immune activation are effectively solved. The nanogel adjuvant can efficiently load various antigens to form a stable nano vaccine, activate an immune microenvironment and provide more means and thoughts for vaccine development.

The invention discloses a protein capable of inducing a plant immune activation function and application of the protein in disease control, the gene sequence of the protein capable of inducing the plant immune activation function is shown as SEQ ID NO: 1, and the amino acid sequence of the protein is shown as SEQ ID NO: 2. According to the invention, a novel plant immune activator protein CgSsp16 secreted by colletotrichum gloeosporioides is identified, can be identified by plants, stimulates a plant immune response mechanism, triggers broad-spectrum resistance of host plants to various pathogens and improves disease resistance of various plants; the compound is expected to be developed into a novel biopesticide to be applied to green and sustainable production of agriculture.

The application provides a compound microbial agent for preventing and treating bacterial diseases of fruits and vegetables and a preparation method thereof, wherein the compound microbial agent comprises Brevibacillus brevis, Pseudomonas chlororaphis and Streptomyces; wherein the ratio of the viable bacterial count of the Brevibacillus brevis, the Pseudomonas chlororaphis and the Streptomyces is (1-3):(2-4):(1-2). The Brevibacillus brevis directly inhibits bacteria by secreting antibacterial peptides, the Pseudomonas chlororaphis competes for ecological niches through iron carriers, and the Streptomyces produces antibiotics, so that multiple strains form a "bacteriostasis-competition-immune activation" multiple mechanism, thereby achieving efficient prevention and treatment of bacterial diseases of fruits and vegetables.

This application relates to the field of tumor treatment technology, specifically to a drug combination and evaluation method for improving the sensitivity of MSS CRC to anti-PD-1 / PD-L1 therapy. The drug combination comprises vancomycin and an immune checkpoint inhibitor. Vancomycin is used to remodel the gut microbiota and reduce L-asparagine levels; the immune checkpoint inhibitor is used to activate CD8. + T-cell anti-tumor response. By combining vancomycin with immune checkpoint inhibitors, the antigen-presenting capacity of dendritic cells is enhanced, thereby increasing the sensitivity of MSS CRC to anti-PD-1 or anti-PD-L1 immunotherapy. This application focuses on the upstream initiation link of gut microbiota-metabolites-dendritic cells-immune activation, relieving the inhibition of dendritic cell antigen presentation by L-asparagine and enhancing CD8+. + T cell activation and tumor immune response enhance the sensitivity of MSS-type colorectal cancer to anti-PD-1 / PD-L1 therapy.

This invention discloses a lipid nanoparticle co-delivery system based on phenolic hydroxyl lipids and a manganese adjuvant. Addressing the shortcomings of traditional HPV therapeutic peptide vaccines—weak immunogenicity, easy degradation and inactivation in vivo, low bioavailability of manganese ion adjuvants making spatiotemporal co-delivery with antigens, and poor encapsulation efficiency and insufficient biosafety of conventional lipid nanocarriers—this invention constructs an integrated nanovaccine delivery system by embedding phenolic hydroxyl functional lipids into a nanocarrier framework, synergistically loading HPV E6 / E7 specific antigen peptides and manganese ion immune adjuvants. This system achieves efficient delivery, immune activation, and anti-tumor efficacy, integrating the functions of efficient antigen delivery, potent immune activation, and precise anti-tumor action. The preparation process is simple and exhibits excellent stability, overcoming the limitations of traditional HPV peptide vaccines with poor efficacy when used alone. It has broad research value and clinical translation prospects in the field of precision immunotherapy for HPV-related cervical cancer, head and neck squamous cell carcinoma, and other malignant tumors.

The application provides a self-driven BCG-nanoparticle complex and a preparation method thereof, and belongs to the fields of biological medicine and nanomaterials. The complex is a composite of BCG and cerium oxide nanoparticles with urease activity, the cerium oxide nanoparticles are coupled to the surface of the BCG in an asymmetric distribution through modified polyethyleneimine, and specifically, the surface of the BCG is connected to several modified polyethyleneimine derivatives through chemical bonds and electrostatic adsorption, and the polyethyleneimine derivatives wrap the cerium oxide nanoparticles through electrostatic adsorption. The complex can be self-driven by using the gas release and ion concentration change caused by the catalytic decomposition of urea in the environment, significantly enhances the adhesion and retention of BCG on the bladder wall, effectively overcomes the defects of low delivery efficiency and insufficient immune activation of traditional BCG therapy, simultaneously improves the tumor immune microenvironment, and can be used for preparing high-efficiency and low-toxicity bladder cancer treatment drugs.

The application belongs to the technical field of biological medicine, and particularly relates to application of an inhibitor for inhibiting lactic acid modification of lysine at the 249th position of HSP60 protein. The application provides application of the inhibitor for inhibiting lactic acid modification of lysine at the 249th position of HSP60 protein in preparation of a medicine for preventing and / or treating psoriasis, and an amino acid sequence of the HSP60 protein (heat shock protein 60) is shown as SEQ ID NO. 1. The application provides a brand-new, mechanism-driven psoriasis treatment target, lactic acid modification of lysine at the 249th position of HSP60 protein. By inhibiting the specific modification, the purpose of precise intervention and treatment from an upstream of the disease is achieved by stabilizing mitochondrial function and blocking intrinsic immune activation triggered by metabolic stress.

The invention provides an anti-cancer medicine and food homologous composition and a preparation method thereof. The composition is prepared from the following components in parts by weight: 5 to 10 parts of lipoic acid, 30 to 50 parts of nano curcumin, 2 to 7 parts of berberine, 50 to 100 parts of beta-glucan, 15 to 35 parts of polymethylacrylic acid, 15 to 25 parts of herba hedyotidis diffusae extract, 7 to 15 parts of scutellaria barbata baicalein, 25 to 55 parts of astragalus polysaccharide, 8 to 18 parts of coix seed ester and 10 to 15 parts of cordyceps cicadae. Through a space-time targeting synergistic release mechanism of a bionic nanocellulose skeleton and in combination with pH / enzyme double-response intelligent regulation and control, three-stage precise synergistic effects of oxidation resistance, apoptosis promotion and immune activation are realized, the limitation that a traditional medicinal and edible composition is poor in targeting property, low in synergistic efficiency and uncontrollable in toxicity is broken through, and the medicinal and edible composition has a broad application prospect. High-efficiency and low-toxicity tumor multi-channel synergistic intervention is achieved in a natural component system for the first time, and the actual effect of the whole medicinal and edible composition on cancer and swelling resistance is improved.

The invention belongs to the field of food, particularly relates to a nutritional composition and application thereof in improving immune disorder, and more particularly relates to application of the nutritional composition in preparing food for improving filial generation body inflammatory factor level disorder caused by maternal immune activation. The nutritional composition comprises essential active ingredients shown as the following (i) and (ii): (i) a neutral fucosylated breast milk oligosaccharide, (ii) a neutral non-fucosylated breast milk oligosaccharide; wherein the neutral fucosylated breast milk oligosaccharide at least comprises 2 '-fucosylated lactose, and the neutral non-fucosylated breast milk oligosaccharide at least comprises lactose-N-neotetraose; in addition, in the nutritional composition, the mass ratio of the lactose-N-neotetraose to the 2 '-fucosyllactose is 1: (1-8), and the 2'-fucosyllactose and the lactose-N-neotetraose can achieve a synergistic effect to regulate filial generation immunity.

The invention discloses a macrophage-targeting lipid nanoparticle and application thereof in malignant tumor treatment, ID3 mRNA is delivered through the lipid nanoparticle, firstly, an ID3 sequence is subjected to codon optimization to improve the expression efficiency and stability of ID3 protein, and the core treatment effect is enhanced; the lipid composition and the targeting ligand of the nanoparticles are further optimized, and mannose modified PEG lipid material (DSPE-PEG2000-Mannose) is specifically combined with the CD206 receptor on the surface of the macrophage, so that the targeting property and the transfection efficiency of the delivery system are remarkably improved. The ID3 mRNA is delivered to the macrophages by utilizing the lipid nanoparticles of the targeted macrophages, so that the tumor cells can be effectively swallowed and killed, the in-situ treatment of pancreatic cancer is realized, and better tumor inhibition and immune activation effects are achieved.

The present application relates to the technical field of polymer chemistry, and particularly relates to a responsive dendritic polyamino acid modified polyurethane and a preparation method and application thereof.The responsive dendritic polyamino acid modified polyurethane has a structure shown in formula I.The responsive dendritic polyamino acid modified polyurethane provided by the present application can specifically expose positive dendritic polylysine in the unique acidic environment of tumor tissue, trigger immunogenic death of tumor cells, release tumor antigens, and comprehensively activate an anti-tumor immune response.Meanwhile, the positive dendritic polylysine causes an increase in reactive oxygen species (ROS) of tumor cells, oxidizes a diselenium bond in the polyurethane into selenic acid, reduces the expression of immune checkpoints of tumor cells, reverses the immunosuppressive microenvironment of tumor tissue, realizes synergistic treatment of immune activation and reversal of the tumor immunosuppressive microenvironment, and realizes a better tumor immunotherapy effect.

The application discloses a plant immunity elicitor protein PpAE4 and application thereof, the protein can induce plant resistance, and can be applied to the field of plant disease prevention and treatment as a plant immunity activator. The amino acid sequence of the protein is shown as SEQ ID NO:2. High-concentration protein can be obtained by using an engineering strain for expression, and the protein can be used for treating plants to improve the disease resistance of the plants to soybean rust fungi, and the required concentration is low, the effect is quick, and the action time is long. The PpAE4 provides a new way for improving the disease resistance of plants and preventing and treating plant diseases.

The invention discloses sea-buckthorn, radix astragali and yeast beta-glucan granules and application thereof, and relates to the technical field of food health care, and the sea-buckthorn, radix astragali and yeast beta-glucan granules are prepared from the following raw materials: sea-buckthorn, radix astragali, yeast beta-glucan, American ginseng, radix salviae miltiorrhizae, fructus lycii, flos sophorae, fructus crataegi, xylitol, erythritol, cordyceps militaris, inonotus obliquus, radix polygonati officinalis, rhizoma dioscoreae, radix ophiopogonis and fructo-oligosaccharide. According to the invention, a three-dimensional efficacy system of immune activation, inflammation inhibition and intestinal repair is constructed through scientific proportioning of raw materials such as sea-buckthorn, astragalus membranaceus, yeast beta-glucan, cordyceps militaris and inonotus obliquus. The core components have a synergistic effect, so that not only can the activity of immune cells be activated and the immunity of the organism be improved, but also the release of inflammatory factors can be inhibited, the inflammatory response can be relieved, and meanwhile, the intestinal beneficial bacteria can be proliferated, the intestinal mucosa can be repaired and the intestinal micro-ecology can be improved. Compared with traditional medicinal and edible granules with a single effect, the product can meet the health requirements of people with different constitutions and is richer in adaptive scene.

Methods for the use of prodrugs of itaconic acid and 1- and 4-methyl itaconic acid for inducing hair growth and treating an inflammatory, or immune activation (adaptive or innate), skin condition or other condition associated with hair loss are disclosed.

The application discloses double-gene engineered mesenchymal stem cells and application thereof, relates to the technical field of biological medicine. The double-gene engineered mesenchymal stem cells provided by the application co-express CXCR4 and TNFSF14 proteins, exhibit enhanced tumor tropism and immune-mediated anti-tumor activity. Specifically, based on the principle that CXCR4 can enhance the active homing ability of mesenchymal stem cells to gastric cancer lesions expressing its ligand SDF-1 (SDF-1 / CXCL12), and TNFSF14 (LIGHT) can interact with HVEM and LTbetaR receptors to promote the activation of T cells and NK cells, the mesenchymal stem cells co-expressing CXCR4 and LIGHT overcome the defects of insufficient targeting of natural MSCs and weak immune activation ability, and have excellent anti-tumor effect.

The invention discloses a macrophage immune activation method based on aggregate mediated magnesium ion delivery. The method comprises the following steps: in a buffer environment containing magnesium ions, preparing a biomolecular aggregate formed by compounding polyarginine and polyadenylic acid through liquid-liquid phase separation, and enriching the magnesium ions by the aggregate through multivalent chelation; diluting the aggregate loaded with high-concentration magnesium ions in a cell culture medium to obtain a biomolecular aggregate suspension; and sequentially adding the target cell suspension and the biomolecular aggregate suspension into a cell culture dish, fully mixing, and then transferring the cell culture dish into a carbon dioxide cell incubator for standing culture. According to the method, the biomolecular aggregate loaded with the high-concentration magnesium ions is co-cultured with the cells, and the high-concentration magnesium ions are delivered into the cells in a short time, so that the immune level of the cells is improved, and the activity and safety of the cells are ensured.

The invention belongs to the technical field of biological pharmacy, and particularly discloses a Siglec-15 affinity peptide and application thereof. According to the invention, a phage display heptapeptide library high-throughput screening technology is adopted, Siglec-15 affinity peptide 7-8 is obtained through multiple rounds of screening, and the Siglec-15 affinity peptide 7-8 is optimized and modified to obtain a reversed sequence flip peptide d-7-8. Experimental results show that the Siglec-15 affinity peptide can be used for affinity of Siglec-15 protein and blocking the interaction between Siglec-15 and a ligand Sialyl-Tn of Siglec-15, so that the anti-tumor effect is achieved; an in-vitro cell level experiment shows that the Siglec-15 affinity peptide has a relieving effect on inhibition of Siglec-15 on CD8 + T cell proliferation, has an obvious immune activation effect, does not have obvious toxic or side effects, can be used for preparing an anti-tumor drug or a detection reagent taking Siglec-15 as a target spot, and has a relatively good medical application prospect.

The invention relates to the field of biomedical technologies and pharmaceutical preparations, and discloses a TLR9 + HA201 composite adjuvant and a preparation method and application thereof, and the TLR9 + HA201 composite adjuvant freeze-drying preparation comprises the following components: a TLR9 + HA201 composite adjuvant, a TLR9 + HA201 composite adjuvant, a TLR9 + HA201 composite adjuvant freeze-drying agent, a TLR9 + HA201 composite adjuvant freeze-drying agent, a TLR9 D-(+)-trehalose; l-glutamic acid; a citrate buffer solution; the pH value of the aqueous solution to be freeze-dried is 6.5-7.5, the concentration of the D-(+)-trehalose is 8% w / v-12% w / v, the concentration of the L-glutamic acid is 0.8% w / v-1. 5% w / v, and the concentration of the citrate buffer solution is 15-25 mM. Through the synergistic effect of D-(+)-trehalose and L-glutamic acid in a specific citrate buffer system, efficient protection on the biological activity of the TLR9 + HA201 composite adjuvant is achieved, and the freeze-dried preparation shows the immune activation ability basically consistent with that before freeze-drying after being redissolved.

The present invention provides a composite molecule, a nucleic acid, a vector, a host cell, and a pharmaceutical composition, and uses of the composite molecule, the nucleic acid, the vector, the host cell, and the pharmaceutical composition in preparation of drugs for treating cancers. The composite molecule comprises an anti-tumor antibody domain, a linker, and pro-IL-15; the anti-tumor antibody domain is linked to the pro-IL-15 by means of the linker; the anti-tumor antibody domain is a complete antibody against an immune checkpoint molecule, a tumor antigen molecule or an immune activation molecule, or a nano antibody or an antigen binding fragment thereof; the linker is a polypeptide linker or a non-peptide linker; the pro-IL-15 is a fusion protein comprising IL-15, an IL-15Rα sushi domain, and a linker peptide, and optionally comprising an IL-15Rβ extracellular domain; and the IL-15Rβ extracellular domain, the IL-15, and the IL-15Rα sushi domain are linked by means of the linker peptide.

The present invention covers aminothiazole compounds of general formula (I), in which R1, R2, R3 and R4 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and / or prophylaxis of diseases, in particular of diacylglycerol kinase zeta (DGKζ) regulated disorders, as a sole agent or in combination with other active ingredients.

The invention discloses an application of FGSG09291 protein and a coding gene thereof in improving plant disease resistance, and belongs to the technical field of plant immune induced resistance. According to the invention, a novel FGSG09291 protein with a plant immune activation function is found from fusarium graminearum, and the FGSG09291 protein can promote plant active oxygen outbreak and callose accumulation and provide basic immune response for plants; in addition, high expression of the PR1a gene, the WRKY70 gene and the LOX3 gene can be induced, the PR1a gene and the WRKY70 gene are genes of a salicylic acid pathway, and the increase of salicylic acid can improve the broad-spectrum resistance of plants. Experiments prove that the prevention and control effect of corn on dwarf mosaic disease can be enhanced by externally applying the FGSG09291 protein.

The invention relates to shigella flexneri as well as related serotype and application of a preparation of the shigella flexneri in preparation of anti-tumor immune activation and treatment medicines. The shigella flexneri and the preparation thereof disclosed by the invention can improve a tumor immune microenvironment by activating anti-tumor immune response of an organism so as to inhibit tumor growth, and are suitable for prevention and / or treatment of various tumors; the strain and the preparation thereof can be independently used and can also be combined with existing tumor therapies such as chemotherapy, radiotherapy and immunotherapy to synergistically enhance the anti-tumor curative effect; the invention provides a new microbial resource and strategy for tumor immunotherapy, and has an important clinical application prospect.

HIV-1-related immune activation is not only associated with AIDS progression, but also with CD4+ after cART treatment. + Insufficient T cell recovery is a contributing factor. This invention focuses on nicotinamide adenine dinucleotide (NAD) precursors and their potential in modulating host immune cells against HIV-1. Treatment with nicotinamide mononucleotide (NMN) inhibits HIV-1 infection at the post-transcriptional stage by targeting ACH-2 and primary CD4 cells. + Viral production in T cells. On one hand, the NMN treatment preferentially reduces CD25. + CD4 + Intracellular HIV-1 p24 production in T cells. On the other hand, using in vitro, ex vivo, and in vivo models, NMN consistently inhibited the expression of late T cell activation markers, including CD25 and HLA-DR. Furthermore, NMN works by assisting the production of CD4+. + T-cell regeneration to improve the therapeutic efficacy of cART in HIV-1-infected humanized mice.

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.