31 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 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.

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.

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.

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 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.

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.

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 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.

Methods and compositions for priming a dimerizing agent regulated immunomodulatory complex for signaling by inducing the multimerization of at least a first fusion protein and a second fusion protein to thereby form the dimerizing agent regulated immunomodulatory complex are described. The methods and compositions utilize dimerizing agent dosing schedules designed to: (i) maintain specified blood trough levels of the dimerizing agent, (ii) allow activation of the immunomodulatory complex; (iii) reduce or avoid potential immunosuppressive effects of the dimerizing agent, (iv) reduce or avoid immune cell exhaustion, and / or (v) reduce or avoid side effects associated with activation of the immunomodulatory complex.

It is the object of the present invention to provide prinabulin and one or more G-CSF agents for the treatment of chemotherapy-induced neutropenia, stimulation of neutrophil survival, reduction of bone pain induced by G-CSF agents and immunosuppressive effects induced by G-CSF agents.SOLUTION: It has been found that Plinabulin and one or more G-CSF formulations can be provided for treatment of chemotherapy-induced neutropenia, stimulation of neutrophil survival, reduction of bone pain induced by G-CSF formulations and immunosuppressive effects induced by G-CSF formulations, and that docetaxel-induced neutropenia can be reduced by co-administration of Plinabulin and one or more G-CSF compounds.SELECTED DRAWING: Figure 1

The invention belongs to the technical field of tumor cell immunotherapy, and particularly relates to preparation and application of a TGF-beta activated CAR-NK cell. The preparation method disclosed by the invention comprises the following steps: constructing lentivirus expression plasmids, transforming, screening, packaging viruses, preparing virus particles, infecting cells, amplifying the cells and the like. The CD276CAR.TGFBR2-KO-T4z-NK92 cell constructed by the invention can be effectively combined with a receptor protein of TGF-beta and a CD276 antigen, the NK cell is activated by TGF-beta1 to avoid tumor escape of the CAR-NK cell caused by antigen deletion or down-regulation, and the immunosuppression effect of the TGF-beta1 is thoroughly avoided, so that a certain technical foundation is laid for a prevention and treatment technology for improving esophageal squamous cell carcinoma. The infiltration condition of the NK-92 cells in tumor tissues is evaluated through flow cytometry, and the tumor infiltration rate of the CD276CAR.TGFBR2-KO-T4z-NK92 cells is obviously higher than that of other control cells. In general, the data shows that the CD276CAR.TGFBR2-KO-T4z-NK92 cells have excellent anti-tumor activity in vivo and in vitro, and the durability of the CD276CAR.TGFBR2-KO-T4z-NK92 cells in tumors is enhanced.

This invention provides compositions and methods for treating cancer using CAR T cells. [Solution] Provided are a) a chimeric antigen receptor (CAR) comprising an antigen-binding domain specific to a cell surface antigen; and b) an isolated nucleic acid sequence encoding an armoring molecule that, when expressed on the surface of a cell in the tumor microenvironment, counteracts the immunosuppression of the cell. In another embodiment, a cell is provided comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) and a TGFβRIIDN armoring molecule expressed on the surface of the cell.

It was discovered that ICIs elevated extracellular NAD levels and conferred cancer cells resistance to ICIs. It was also discovered that NAMPT was induced by IFN-y and ICIs resulting in an increase of extracellular NAD level, which could be reduced by NAMPT knockdown. NAMPT deficiency in HCC sensitized tumors to anti-PD-1 treatment. It was further discovered that extracellular NAD promoted T cell apoptosis, exhaustion, and T cell differentiation to regulatory T cells. The blockade of P2X7R reversed the immunosuppressive effect of NAD and worked effectively in combination with immunotherapies, indicating that it can be a combination therapeutic approach for ICI-resistant tumors. It was shown that serum NAD level can be a predictive biomarker for ICI responses in HCC. Overall, extracellular NAD was shown to act as an immunosuppressive metabolite that could serve as a biomarker for ICI responses and the P2X7R can be a therapeutic target to improve ICI efficacy.

Disclosed are a genetically modified cell in which a nucleic acid encoding a CD40L binding agent (e.g., a stefin A protein variant specifically binding to CD40L or a fusion protein including the same) is introduced into a host cell and uses thereof. Provided are genetically modified cells expressing a CD40L binding agent enabling secretion thereof, expression thereof on a cell membrane, and / or intracellular localization thereof, and are thereby capable of reducing or inhibiting the activity of CD40L. Provided genetically modified cells may inhibit T-cell activity and B-cell activity and exhibit an immunosuppressive effect, and may be thus useful for the prevention or treatment of immune diseases such as autoimmune diseases or inflammatory diseases.

Disclosed are methods for reducing the immunosuppressive effect of myelin derived suppressor cells in adoptive cell therapy.

A targeted IL12 fusion protein, an isolated nucleic acid molecule, a vector, a cell, a pharmaceutical composition, a production method, a tumor treatment method, and a pharmaceutical use; compared with the systemic immune system, the targeted IL12 fusion protein selectively activates a tumor microenvironment, particularly inducing Treg cells in the tumor microenvironment to secrete IFNg, thereby reducing or eliminating the immunosuppressive effect thereof.

The present invention belongs to the fields of tumor therapy and molecular immunology, and provides an anti-CTLA4 monoclonal antibody or antigen binding fragment thereof, a pharmaceutical composition thereof and use thereof. The monoclonal antibody of the present invention can block the binding of CLTA4 to B7, relieve the immunosuppression on the body by CTLA4, and activate T lymphocytes.

The invention belongs to the technical field of medicines, and particularly discloses a novel immunosuppressant and application thereof, and the novel immunosuppressant is pinomoic acid separated and identified from glossy privet fruits. The invention relates to pomolic acid (PA) separated and identified from glossy privet fruit, which has an immunosuppressive effect, plays an immunosuppressive role by inhibiting the expression of proinflammatory factors and promoting the expression of anti-inflammatory factors, and also has application in preparation medicines for treating inflammatory disease models (such as acute lung injury). The PA can obviously inhibit the expression of proinflammatory factors (IL-1beta, IL-6, TNF-alpha and iNOS) and promote the expression of anti-inflammatory factors (IL-10), and can obviously improve the survival rate of acute lung injury model mice, reduce lung tissue pathological injury and relieve inflammatory response, which indicates that the PA has a very good immunosuppression effect. The invention provides a theoretical basis for developing novel immunosuppressants, and has potential application value.