47 results about "Immunosuppressive effect" patented technology

This document provides methods and materials involved in treating cancer. For example, methods and materials for modulating (e.g., increasing or decreasing) an interleukin-1 (IL-1) signaling pathway (e.g., an IL-1βsignaling pathway) during an adoptive cell therapy (e.g., a chimeric antigen receptor (CAR) T cell therapy) are provided. In some cases, one or more inhibitors of an interleukin-1 receptor antagonist (IL-1RA) polypeptide can be used to increasing IL-1 signaling (e.g., to reduce immunosuppression of the administered cells). In some cases, CAR T cells having a reduced level of an interleukin 1 receptor, type I (IL-1R1) polypeptide can have decreased IL-1 signaling (e.g., to reduce T cell toxicity associated with the administered cells).

The invention relates to a leukocyte product, frozen leukocytes, a preparation method and application of the leukocyte product and the frozen leukocytes in preparation of medicines for inhibiting inflammation. The leukocyte product comprises one or more non-viable leukocytes from blood, the non-viable leukocytes carry cytokine receptors but basically do not have proliferation capacity, and the cytokine receptors can be combined with cytokines which can be combined with normal blood leukocytes. The inactive leukocytes may be frozen leukocytes. The frozen leukocytes can be obtained by quickly freezing in-vitro normal blood leukocytes, and the quick freezing treatment temperature is ultralow temperature. The inactive leukocytes or frozen leukocytes in the leukocyte product can recognize and be competitively combined with the cytokines with normal immune cells without additionally secreting new cytokines, so that the cascade amplification effect of inflammation cannot be caused. The leukocyte product or frozen leukocyte can play an immunosuppressive role, has no obvious toxic or side effect, and can be used for preparing medicines for inhibiting inflammation, such as medicines for inhibiting severe inflammation.

The present application relates to the application of open-cage borane compounds in the preparation of immunosuppressants, belonging to the technical field of biological medicine. The open-cage borane compounds of the present application include nest borane compounds and / or spider web borane compounds, and the pharmaceutically acceptable solvates or pharmaceutically acceptable complexes of the nest borane compounds and the spider web borane compounds. The open-cage boron clusters of the present application have dehydrogenase-like activity, can catalyze the dehydrogenation reaction of hydroxyl-containing organic substrates in a biological system, promote the conversion of NAD(P) + to NAD(P)H, further improve the intracellular oxidation-reduction ratio, induce cell redox stress, and further reshape the metabolic pattern of HSCs from the source, promote the differentiation of immune cells to immunosuppressive phenotype, and play an immunosuppressive role.

The invention discloses an optimization method for in-vitro amplification culture of mesenchymal stem cells, and belongs to the technical field of stem cell culture. The optimization method comprises the step of adding a substance for enhancing TLR3 gene expression in the in-vitro amplification culture process of the mesenchymal stem cells so as to improve the immunosuppression effect of the in-vitro cultured mesenchymal stem cells. In-vitro experiments show that through intervention of a TLR3 activator PIPC, the immunosuppression function of the P15MSC is successfully recovered, the immunosuppression effect of the P5MSC is further enhanced, an effective optimization strategy is provided for amplification and culture of the MSC before clinical application, the immunosuppression effect of the MSC is favorably maintained, the effectiveness of the MSC in treatment of GvHD is improved, and the immunosuppression effect of the P15MSC is improved. And a new solution is provided for treatment of immune diseases such as GvHD.

This invention relates to compositions, and uses and methods thereof, with therapeutic deciparticles. Described herein are deciparticle (nanoparticle) compositions composed of an amphiphilic compound complexed with an auxiliary compound such as a biologically active molecule. Deciparticles of this invention are active drugs having potency for anti-tumor effects and for immunosuppression. This invention is also directed to amphiphilic compounds useful for making deciparticle complexes.

Tyrosine Inhibitors with Immunosuppressive Activity in Human Neonatal Keratinocyte Progenitors; Embodiments relate to tyrosine inhibitors that exhibit immunosuppressive activity in human neonatal keratinocyte progenitors. Particular embodiments feature the immunosuppressive effects of a decapeptide and / or oxyresveratrol, as measured by two different methods: blockade of stimulated cell growth, and inhibition of cytotoxic killing.

The invention relates to the technical field of biology, in particular to an in-vivo editing and metabolism reprogramming nano drug-loaded material for targeting macrophages as well as a preparation method and application of the in-vivo editing and metabolism reprogramming nano drug-loaded material. On the basis of a metal organic framework (MOF) material, CAR mRNA molecules targeting DLL3 are loaded in the MOF material, a macrophage-derived cell membrane is coated outside the MOF material, and the nano drug-loading material with the macrophage targeting capability is constructed. The material has the effects of specifically swallowing and killing tumor cells, improves the immunosuppression effect of a tumor microenvironment by utilizing the immune activation effects of succinic acid and manganese, and synergistically promotes the killing effect on small cell lung cancer. The macrophage in-vivo editing technology designed by the invention is a novel safe, efficient, simple and convenient tumor immunotherapy technology, overcomes the defect that CAR-T cannot enter the interior of a solid tumor, and solves the problem of tedious cell in-vitro amplification and gene editing procedures in the conventional CAR immunotherapy process; and a new strategy is provided for immunotherapy of small cell lung cancer with limited treatment means.

To provide a population of cord blood-derived regulatory T cells expanded ex vivo. To provide a method for producing a population of cord blood-derived regulatory T cells expanded ex vivo, and a method for using the same.SOLUTION: Provided is a population of human Treg cells comprising at least about 1 * 10 8 human Treg cells, wherein (i) ≥ 60% are CD4 + CD25 + and (ii) ≤ 10% are CD4 - CD8 +, wherein said human Treg cells are immunosuppressive.SELECTED DRAWING: Figure 1

The present invention relates to a method for mass-producing immunosuppressive T cells using human serum albumin. According to the present invention, when peripheral blood stem cells (PBSCs) obtained from individuals administered with granulocyte colony-stimulating factor (G-CSF) are cultured in a medium containing human serum albumin (HSA) or HSA and mercaptoethanol, immunosuppressive T cells having immunosuppressive effects can be mass-produced. It has been confirmed that the immunosuppressive T cells exhibit excellent therapeutic effects against acute graft-versus-host disease. Therefore, the present invention is expected to be useful in the treatment of immune diseases such as acute graft-versus-host disease.

The present disclosure relates to cellular therapy products comprising mesenchymal lineage precursor or stem cells and potency assay for these products. The present disclosure also relates to methods for treatment of immune or inflammatory disorders, and treatment or prevention of graft versus host disease (GVHD), or one or more symptoms associated with GVHD, by administration of mesenchymal lineage precursor or stem cells.

The invention discloses a crocodile blood composition for improving immunity and application. The composition provided by the invention comprises the following raw materials in parts by weight: 30-60 parts of crocodile plasma powder, 1-7 parts of liquorice, 5-10 parts of radix asparagi, 3-10 parts of schisandra chinensis, 4-10 parts of codonopsis pilosula, 8-15 parts of lucid ganoderma, 2-8 parts of American ginseng and 1-5 parts of vitamin C. The composition is rich in various active substances capable of improving immunity, and can improve the immunity of the crocodile blood, promote the release level of immunomodulatory factors TNF-alpha and IL-2, increase the total number of spleen and lymphocytes and the volume of white marrow and lymph node cortex of the spleen through the cooperation of specific Chinese herbal medicine components and bioactive components in the crocodile blood, and improve the immunity of the crocodile blood. The immunosuppression effect is reduced, and the lymphocyte proliferation capacity is remarkably improved. The composition provided by the invention is green and safe in raw materials, rich in nutrition, and capable of enhancing the effect of crocodile blood and enhancing the immunity of the organism.

The application discloses application of pulegone as an effective component in an immunosuppressant, and the pulegone with significant calcineurin (CN) inhibiting activity is screened from the Schleichera oleosa Kurz, the immunosuppressive effect of the pulegone is equivalent to that of cyclosporine A which is widely used in clinic, mechanism research shows that the pulegone targets CN / NFAT signal path to play the immunosuppressive activity, and the pulegone has very weak cytotoxicity to spleen cells, and is a high-efficiency and low-toxicity immunosuppressant.

Compositions and methods for preventing or treating autoimmune diseases are provided. The composition comprises a binding partner configured to bring LAG-3 and a T cell receptor closer to each other than in the absence of the binding partner, thereby providing an immunosuppressive effect on activated T cells.

The invention relates to the technical field of Tibetan medicines, in particular to a preparation containing Tibetan medicine musk, a preparation method of the preparation and application of the preparation in preparation of liver cancer medicines. The preparation is prepared from the following raw materials: musk, swertia mussotii, rheum tanguticum, dracocephalum tanguticum, delphinium delphinium, phyllanthus emblica, salviae miltiorrhizae, herpetospermum pedunculosum, saussurea hypoglauca, saffron crocus, trogopterus dung, fructus chebulae and plantago asiatica. According to the invention, a plurality of medicinal materials are compatible, all the raw materials have a synergistic effect, the effects of compound components are effectively exerted, and the traditional Chinese medicine composition can resist cancer, protect liver, clear away heat and toxic materials and inhibit tumor growth, has a good anti-liver cancer effect and does not generate an immunosuppressive effect on a body.

The invention provides a recombinant mesenchymal stem cell for immunoregulation and application of the recombinant mesenchymal stem cell in preparation of a product for preventing and / or treating septicopyemia, relates to the technical field of biological medicines, and aims to improve the expression quantity of IDO1 in a receptor mesenchymal stem cell to obtain the recombinant mesenchymal stem cell. The IDO1 expression level and enzyme activity of the MSC are remarkably improved through a genetic engineering means, meanwhile, the expression levels of TSG6, PTGS2, IRF1 and IL-10 are remarkably increased, it is indicated that the immunoregulation program of the MSC is comprehensively activated, and the immunosuppression effect of the MSC is enhanced; animal tests prove that the recombinant mesenchymal stem cells inhibit systemic inflammatory response, significantly reduce the death rate of septicopyemia mice, promote immune homeostasis recovery, avoid side effects caused by excessive immunosuppression, and realize a bidirectional immunoregulation effect.

This invention discloses an engineered attenuated Salmonella VNP-SNase, its preparation method, and its applications, including methods and compositions for treating various solid tumors or metastatic tumors. Specifically, engineered attenuated Salmonella capable of expressing and secreting SNase is recruited to the tumor microenvironment through tumor targeting, specifically degrading intratumoral neutrophil extracellular traps (NETs), weakening the killing effect of NETs on Salmonella, increasing its intratumoral colonization, and simultaneously improving the tumor-promoting and immunosuppressive effects caused by NETs, ​​while effectively preventing bacteria from off-target into normal organs. By releasing SNase to activate / regulate the immune system and directly / indirectly inhibit tumors, it can act as an effective immune effector.

The present invention provides methods and materials for treating mammals (e.g., humans) that have or are at risk of developing a disease or condition characterized by tissue inflammation and / or degeneration. [Solution] For example, mesenchymal stem cells (MSCs) that express tissue-targeting antigen receptors (e.g., chimeric antigen receptors) capable of exerting immunosuppressive effects in targeted tissues are provided, as well as a method using such MSCs.

The present disclosure relates to a Treg-cell-targeting IL12 fusion protein, a corresponding nucleic acid molecule, vector, cell and pharmaceutical composition, a corresponding production method, a corresponding method for treating tumors, and the pharmaceutical use. Relative to a systemic immune system, the Treg-cell-targeting IL12 fusion protein of the present disclosure selectively activates the tumor microenvironment, especially inducing the secretion of IFNg by intratumoral Treg cells, thereby reducing or eliminating the immunosuppressive effect thereof.

The invention discloses a construction method and application of an African swine fever virus A137R protein eukaryotic expression vector with an immunosuppressive effect, and relates to the technical field of virus coding protein expression and function research biology. According to the eukaryotic expression vector, ASFVGZ201801 strain genome DNA serves as a template, a specific primer is adopted for PCR amplification, PCR fragments are recycled and then connected with a pCAGGS vector, and positive recombinant plasmids, namely the eukaryotic expression vector with the function of inhibiting the stimulated immune response of cells to IFN-beta, are obtained. The construction method is simple and reasonable, the eukaryotic expression vector can be applied to inhibition of IFN stimulated cellular immune response after transfecting cell expression, and a target spot is provided for research and development of anti-African swine fever virus immunosuppressive drugs.

The invention belongs to the technical field of immunology, and discloses a nanoemulsion adjuvant suitable for a plateau hypoxia environment, a preparation method and application. The nano emulsion adjuvant comprises the following components in 100 parts by weight: 0 to 9.4 parts of D / L-alpha-tocopherol, 0.97 to 6 parts of squalene, 1.94 to 20 parts of tween-80, 0 to 4 parts of span-85 or a substitute surfactant, and the balance of distilled water or a PBS (Phosphate Buffer Solution). The preparation method specifically comprises the following steps: S1, mixing: mixing the corresponding parts of the oil phase, the surfactant and the cosurfactant, and stirring until the mixture is fully dissolved; step S2, emulsifying: slowly dropwise adding sterilized pure water to a preset volume while stirring by adopting a low-energy emulsification method; and standing at room temperature and storing in a dark place to obtain the nano emulsion adjuvant. The compound is mainly applied to preparation of a preparation for improving the immune response capacity under the hypoxia condition. The nanoemulsion adjuvant disclosed by the invention can effectively reverse the immunosuppression effect in a chronic hypoxia environment, comprehensively enhance humoral immunity and cellular immunity response, and solve the problem of limitation of a traditional adjuvant in a specific environment.

Biodegradable particles for interacting with immune cells to generate an immunosuppressive effect are disclosed. The biodegradable particle comprises a polyester or polyester blend with at least one soluble protein or small molecule encapsulated within the particle and at least two types of protein attached to a surface of the particle or to a coating on the surface thereof, which can be used to induce targeting regulatory T cells (Tregs). The at least two types of protein attached to a surface of the particle or to a coating on the surface thereof include a “Signal 1” protein that binds to an immune cell and a “Signal 2” protein that acts as a co-stimulatory molecule to immune cells. The encapsulated protein can be an interleukin and / or a cytokine. Methods of their use for treating a disease or condition, including an autoimmune disease, are disclosed.

This invention discloses an engineered extracellular vesicle and its application in the preparation of products for treating autoimmune diseases. The engineered extracellular vesicle is either an IDO1-overexpressing engineered extracellular vesicle (MSC-IDO1-EVs) or a CSF1-overexpressing engineered extracellular vesicle (MSC-CSF1-EVs). The engineered extracellular vesicles provided by this invention exhibit significant immunosuppressive effects, reducing the secretion of inflammatory cytokines. In animal models, they effectively reduce proteinuria levels, significantly reduce blood dsDNA / ANA levels, effectively alleviate kidney damage caused by autoimmune diseases such as renal immune complex deposition, diffuse thickening of the glomerular basement membrane, and mesangial structural disorder, and reduce overall inflammation levels in mice. The therapeutic effect is significantly superior to that of unmodified MSC-EVs. The engineered extracellular vesicles provided by this invention significantly improve the therapeutic effect on autoimmune diseases.

The invention discloses a hydroxyfluorene compound (formula I) and application thereof, the compound can effectively inhibit a PD-1 / PD-L1 signal channel, an anti-tumor effect is achieved through an immunosuppression effect, the biological activity on the molecular level and the cellular level is remarkably superior to that of an existing medicine, and the hydroxyfluorene compound has a clinical application prospect. # imgabs0 #

The invention discloses a method and a composition for enhancing the curative effect of a PD-L1 inhibitor and reversing immunotherapy drug resistance by blocking CITED1, belongs to the technical field of biological medicine, and creatively discovers that the combination of the CITED1 inhibitor and the PD-L1 inhibitor has a synergistic treatment effect on lung cancer for the first time. The combined strategy not only can effectively reverse T cell function inactivation mediated by CITED1, but also can relieve the immunosuppression effect of PD-L1 and activate anti-tumor immunity, provides an efficient and safer brand-new strategy for overcoming drug resistance, and has a wide clinical application prospect.

The present invention discloses a polycyclic polyisopentenyl phloroglucinol compound and its preparation method and application, belonging to the field of biomedicine technology. The dried aerial part of Hypericum perforatum is used as raw material, and an extract is obtained after diafiltration extraction and concentration, and the extract is suspended in water to obtain a suspension, and a petroleum ether extract is obtained after extraction and concentration; the extract is taken and subjected to positive and reverse phase silica gel column, MCI medium pressure column chromatography, Sephadex LH-20 gel column chromatography separation and high performance liquid chromatography purification to obtain a polycyclic polyisopentenyl phloroglucinol compound, and the structure and configuration of the compound are determined by means of spectral analysis technology, quantum chemical calculation and X-ray single crystal diffraction. This type of compound can inhibit TNF-α protein from exerting an immunosuppressive effect and has the use as an immunosuppressive drug.

This invention relates to compositions, and uses and methods thereof, with therapeutic deciparticles. Described herein are deciparticle (nanoparticle) compositions composed of an amphiphilic compound complexed with an auxiliary compound such as a biologically active molecule. Deciparticles of this invention are active drugs having potency for anti-tumor effects and for immunosuppression. This invention is also directed to amphiphilic compounds useful for making deciparticle complexes.

The invention provides construction and application of a PRRSV (Porcine Reproductive and Respiratory Syndrome Virus) attenuated vaccine double-gene mutant strain, the PRRSV attenuated vaccine double-gene mutant strain weakens the inhibition effect of PRRSV coding non-structural protein on an I-type IFN innate immune signal channel, and mutates amino acid sites with potential immunosuppression effect on non-structural proteins Nsp11 and Nsp12 in a PRRSV HuN4-F112 strain, so as to obtain the PRRSV attenuated vaccine double-gene mutant strain. According to the method, mutant genes maNsp11 and maNsp12 are obtained, on the basis, the double-gene mutant strain vmaNsp1112 is successfully rescued and obtained by utilizing a reverse genetic manipulation technology, and the obtained double-gene mutant strain has genetic stability in an in-vitro passage process, and particularly, compared with a parent strain, the double-gene mutant strain has the advantages that the double-gene mutant strain has the advantages that the yield is high; the double-gene mutation strain vmaNsp1112 can significantly weaken the inhibition effect on the activity of an I-type IFN promoter, a novel genetic engineering vaccine candidate strain with the innate immunosuppression reduction effect is developed, and a foundation is laid for improving the immune efficacy of an existing vaccine and effectively preventing and controlling PRRSV.

This invention relates to the field of biomedicine, specifically to an oncolytic virus targeting TIPE2, its preparation method, and its applications. This invention constructs a recombinant expression vector by inserting a TERTp fragment, a TIPE2 shRNA fragment, and a promoter driving the expression of the TIPE2 shRNA fragment into the vector. This achieves effective oncolytic function without affecting normal cell viability, and also effectively silences the expression of the TIPE2 gene in immunosuppressive cells, weakening the immunosuppressive effect in the tumor microenvironment, reshaping the body's anti-tumor immune response, and thus achieving a more effective tumor treatment effect.

The invention relates to an immunomagnetic substrate for targeted destruction of tumor exosomes and a preparation method and application thereof. The immunomagnetic substrate for targeted destruction of the tumor exosome comprises a Fe3O4 magnetic bead, and the Fe3O4 magnetic bead is sequentially modified with a dendrimer PAMAM, a trimethylamine nitrogen oxide TMAO, an EpCAM aptamer and a curvature sensing peptide AHD. Compared with the prior art, the preparation method has the advantages that the EpCAM aptamer and the curvature sensing peptide AHD are modified on the substrate at the same time, so that the tumor exosome can be specifically recognized and captured, and the tumor exosome can be broken to prevent the tumor exosome from playing an immunosuppressive role. Compared with an antibody and an aptamer, the size of the aptamer is smaller, the EpCAM aptamer is modified on the substrate, it is guaranteed that the substrate has a large number of exosome affinity sites, and the targeting performance on tumor exosomes is improved.

The present invention is directed to compositions and methods to increase the expression of PD-L1 and / or IDO-1 in a population of cells, the modulated cells expressing increased PD-L1 and / or IDO-1, and methods related to the immunosuppressive effects obtained by cells expressing increased PD-L1 and / or IDO-1.