29 results about "Immunologic Suppression" patented technology

The invention belongs to the field of biological medicines, and relates to a drug-loaded nano-vesicle as well as a preparation method and application thereof. The drug-loaded nano-vesicle comprises a vesicle core and a drug-loaded nano-vesicle, wherein the vesicle core comprises siRNA (small interfering Ribonucleic Acid) capable of specifically targeting and silencing an NR1D1 gene; the vesicle membrane is formed by fusing an erythrocyte membrane, a macrophage membrane, cardiolipin, cholesterol and lecithin. The drug-loaded nano-vesicle can specifically target macrophages in a sepsis immunosuppression stage, has an intracellular response release function, recovers BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axis functions by inhibiting NR1D1 expression, reconstructs a macrophage phagocytosis function and lysosome-dependent bacterium removal capability, and can be used for preparing a drug-loaded nano-vesicle with a specific targeting function. The survival rate of sepsis immunosuppression model animals is obviously improved; and the bacterial load is reduced. Compared with a traditional electroporation method, the preparation method disclosed by the invention has the advantage that the encapsulation efficiency of siRNA is remarkably improved.

The invention belongs to the technical field of biological medicine, and relates to pharmaceutical application of an oxidative phosphorylation inhibitor, in particular to application of the oxidative phosphorylation inhibitor in preparation of an immunomodulatory drug, and the immunomodulatory drug has the advantages that the function damage of newborn myeloid-derived suppressor cells caused by antagonism BCG (bacillus calmette guerin) vaccination is inhibited, and the immunomodulatory effect is improved. The compound is used for preventing or treating neonatal immune-related diseases caused by bacillus calmette guerin vaccine inoculation. The invention finds that the BCG can cause damage to the immunosuppression function of the MDSC of the suckling mouse through up-regulation oxidative phosphorylation, and the negative effect caused by inoculation of the BCG can be reversed by using the OXPHOS inhibitor, so that the immunosuppression function of the MDSC of the suckling mouse is successfully recovered in an in-vivo and in-vitro model, and the immune-related adverse reaction caused by inoculation of the BCG is expected to be improved.

This disclosure relates to an immunoglobulin single variable domain (ISVD)-containing modulator that allosterically binds to a three-dimensional (3D) epitope of a protein complex comprising at least one inhibitory immune receptor and at least one corresponding ligand. The modulator regulates cooperativity within such complexes, thereby affecting the binding affinity and downstream signaling pathways. Specifically, the allosteric modulator of this invention induces positive cooperativity in immunoinhibitory receptor-ligand complexes, thus suppressing immune responses in a spatiotemporally restricted manner. Accordingly, these allosteric modulators are useful as therapeutic agents for inflammatory diseases, such as autoimmune diseases, allergic diseases, or graft-versus-host disease (GVHD). Moreover, this disclosure pertains to methods for identifying, selecting, and producing said allosteric modulators.

Soluble TREML1 is involved in many inflammatory diseases and plays an important role in immune suppression. Soluble TREML1 can bind the l-domain of CD11 b and induce an immune suppressive phenotype. Thus, soluble TREML1 may be a good target for treating inflammatory diseases. The present invention relates to antibodies that can reduce soluble TREML1 binding to CD11b+ immune cells and their uses for reversing TREML14nduced immune suppression. Anti-TREML1 antibodies provide a novel and potential therapy for these disease conditions such as cancer.

The application belongs to the field of biological medicine, and relates to a drug-loaded nanovesicle and a preparation method and application thereof. The drug-loaded nanovesicle comprises: a vesicle core comprising siRNA capable of specifically targeting a silenced NR1D1 gene; and a vesicle membrane fused by red blood cell membranes, macrophage membranes, cardiolipin, cholesterol and lecithin. The drug-loaded nanovesicle can specifically target macrophages in the immune suppression stage of sepsis, and has an intracellular response release function. By inhibiting the expression of NR1D1, the drug-loaded nanovesicle restores the functions of BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axes, reestablishes the phagocytosis function of macrophages and the lysosome-dependent bacterial clearance capacity, significantly improves the survival rate of animals in a sepsis immune suppression model and reduces the bacterial load. Compared with a traditional electroporation method, the preparation method of the application significantly improves the encapsulation rate of siRNA.

The invention belongs to the technical field of biological medicine, and particularly relates to application of UFL1 gene in preparation of a product for regulating and controlling tumor immune escape. The invention provides an application of a UFL1 gene in preparation of a product for regulating and controlling tumor immune escape. A nucleotide sequence of the UFL1 gene is shown as SEQ ID NO. 1; the tumors include pancreatic cancer. By taking UFL1 as a target spot and knocking out the UFL1 gene, the quality and volume of pancreatic cancer can be inhibited, and the proportion of CD8 + T cells and the level of immune cell factors can be improved; the proportion of immunosuppression Treg, MDSCs and M2 type macrophages is reduced, and the tumor immune microenvironment is regulated and controlled, so that the immune escape of the tumor is inhibited.

A protein nanospheres and method to treat dysfunction from chemotherapy and immunosuppressive therapy, and a manufacture of fibrinogen-coated albumin spheres (FAS) and High-Fibrinogen Spheres (HFS) which have higher concentrations of fibrinogen molecules per sphere than FAS, and their use for medical treatments. Both kinds of nanoparticles are effective in the mitigation of the toxic effects of certain chemotherapeutic and radiological agents that are typically used in the treatment of cancer, or the treatment of autoimmune diseases, or for patients with both diseases. FAS and HFS can exert their beneficial effects via a variety of mechanisms which match the need of the body for specific cell types, including any of the subgroups of T cells and antibody producing cells, the relative concentration of each kind is vital to the balance between tumor surveillance and autoimmune disease suppression.

The application relates to a composite nanogel and a preparation method and application thereof, in particular to the technical field of biomedical materials. The composite nanogel comprises a nanogel framework and tirapazamine and folic acid loaded on the nanogel framework, wherein raw material components of the nanogel framework comprise a temperature-sensitive monomer and a monomer containing a catechol group. The composite nanogel provided by the application can solve the problems that poor blood vessel adhesion of traditional embolic agents easily leads to embolism recanalization, simple physical embolism is difficult to completely remove hypoxic tumor cells, and existing treatment strategies cannot effectively reverse the immune suppression microenvironment after embolism and activate the systemic anti-tumor immune response.

Described herein are compositions and methods of use thereof for reducing inhibiting B cell activation, B cell proliferation, the production of pathologic, autoimmune or interfering antibodies; and / or for eliciting humoral suppression and / or B cell tolerance in a subject in need thereof by contacting immune cells of the subject or donor immune cells in vivo and / or ex vivo with a composition comprising a Butyrophilin, optionally Butyrophilin A2, or a conjugate or fusion protein comprising said Butyrophilin. The methods include the use of butyrophilin A2 (BTN2A2), a BTN2A2 fragment thereof, a BTN2A2- related isoform, or a BTN2A2-related isoform fragment, or conjugates, and fusion polypeptides containing, preferably which comprise an Fc region comprising one or more mutations which reduce FcR binding and / or which suppress FcRN mediated clearance.

The present invention relates to a method for efficiently differentiating neural stem cells into astrocytes and, more particularly, to a cell conversion-based method for more efficiently differentiating human neural stem cells into astrocytes that exhibit immune response suppression ability within a short period of time. Unlike a conventional method, the method for differentiating neural stem cells into astrocytes by using a differentiation medium containing a combination of several cytokines, according to the present invention, involves a shortened differentiation time and has excellent differentiation efficiency, and the differentiated astrocytes exhibit immune response suppression ability, and thus can be useful as an agent for treating various brain diseases such as degenerative neurological diseases.

Recent studies indicate that sIL7R is involved in the development of autoimmune diseases. The present invention provides methods and compositions for a novel antibody therapeutic against the soluble isoform of the interleukin 7 receptor (sIL7R), a potent driver of self-destructive immune responses that cause autoimmune diseases including multiple sclerosis, lupus nephritis, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, and many other autoimmune diseases. The present invention includes antibodies specific for sIL7R that inhibit SIL7R, a driver of autoimmunity, without inhibiting mIL7R, thereby reducing the severity of or preventing autoimmunity without activating immunosuppressive mechanisms.

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for treating headache and a preparation method thereof. The pharmaceutical composition comprises the following raw materials in parts by weight: 30-40 parts of a pharmaceutical active component, 2-4 parts of a disintegrating agent, 6-11 parts of a filler and 0.2-0.5 part of a lubricant, the active pharmaceutical ingredient consists of porphyridium polysaccharide and manganese gluconate in a mass ratio of 1: (0.5-1). The action mechanisms of the two active components in the pharmaceutical composition are clear and complementary: porphyridium polysaccharide reduces the expression of a proinflammatory factor by inhibiting an NF-kappa B signal channel so as to relieve the stimulation to trigeminal nerve endings, and the porphyridium polysaccharide is mild in action and can avoid the potential influence of strong immunosuppression on the immune system of children; manganese gluconate blocks a CGRP receptor in a targeting manner, directly inhibits nerve ending sensitization and central pain signal transduction mediated by the pain-inducing peptide, and intervenes migraine attack from a key path.

The invention relates to composite nanogel as well as a preparation method and application thereof, in particular to the technical field of biomedical materials. The composite nanogel comprises a nanogel skeleton, tirapazamine and folic acid, the tirapazamine and the folic acid are loaded on the nanogel skeleton, and raw material components of the nanogel skeleton comprise a temperature-sensitive monomer and a monomer containing a catechol group. The composite nanogel provided by the invention can solve the problems that a traditional embolism agent is poor in blood vessel adhesion and easy to cause embolism recovery, hypoxia tumor cells are difficult to thoroughly remove by pure physical embolism, and an immunosuppressive microenvironment after embolism cannot be effectively reversed and systemic anti-tumor immune response cannot be activated by an existing treatment strategy.

The application discloses a use of an active ingredient in repairing heart tissue damage. Specifically, the application discloses an active ingredient which can be used for repairing heart tissue damage and treating diseases related to lymphatic vessel abnormalities, and the active ingredient comprises a TBX1 protein, a coding sequence of the TBX1 protein, or a promoter of the TBX1 protein, or a combination thereof. The TBX1 protein can promote the proliferation of heart lymphatic vessel endothelial cells, play an immune regulation role, promote the establishment of an immune inhibition microenvironment in myocardium after heart tissue damage, inhibit an autoimmune reaction after the heart tissue damage, relieve concurrent heart tissue inflammation, and promote the repair and regeneration of the damaged heart tissue.

The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method and application of a small molecular compound targeting tumor mitochondria. The structural formula of the tumor mitochondria targeting small molecule compound is a small molecule compound CYN-CDA, and the small molecule compound CYN-CDA can improve the high-expression immunosuppression microenvironment of tumor CD47 and PD-L1, and the efficacy of the small molecule compound CYN-CDA is 300 times that of CDA. The CYN-CDA not only solves the bottleneck of tumor immunotherapy, but also starts a multi-mode anti-tumor therapy of immunotherapy and collaborative radiotherapy. The CYN-CDA coated Alb nano preparation formed by self-assembly of a small molecule compound CYN-CDA and albumin has the characteristics of strong tumor mitochondria targeting property, high copper depletion efficiency and the like.

The invention discloses a cell therapy preparation based on tumor specific antigens and application of the cell therapy preparation in solid tumors, and relates to the technical field of biological medicine, the preparation is a composite preparation wrapped by a temperature-sensitive chitosan-hyaluronic acid composite shell layer, and the core of the preparation is composed of double-recognition-domain CAR-T cells, surface modified pH sensitive sustained release microspheres and indoleamine 2, 3-diketone. And preparing the 1, 3-dioxygenase inhibitor. The CAR-T cells are subjected to tumor specific double-recognition-domain targeting design, a TGF-beta switch receptor is fused at the same time to relieve immune suppression mediated by the TGF-beta switch receptor and block the immune suppression effect of an adenosine pathway, and functional modified sustained release microspheres are adopted to mediate cell penetration. Therefore, non-specific recognition of normal cells is avoided, multiple immunosuppression of a tumor microenvironment is comprehensively relieved, accurate targeting of the CAR-T cells to tumor cells is realized, deep infiltration of the CAR-T cells to tumor core areas is realized, and the problems of insufficient targeting specificity and difficult cell infiltration in solid tumor treatment are solved.

The present application relates to a monocyte-carrying type oxygen-producing liposome and a preparation method and application thereof, wherein the preparation method comprises: synthesizing a lipopeptide CP with a cysteine terminal and a lipid RL containing a sulfur ketal domain through a solid-phase polypeptide synthesis method, extracting a thylakoid membrane TK, dissolving and uniformly mixing the lipid components and the lipopeptide CP using an organic solvent, dissolving and uniformly mixing the lipid RL and a STING agonist DA using an organic solvent, and removing the organic solvent in the mixed solution; adding an aqueous solution to the lipid membrane to hydrate, forming a crude liposome suspension, fusing the thylakoid membrane TK to the liposome using an ultrasonic-extrusion method, and obtaining a liposome product. Compared with the prior art, the liposome prepared by the present application can efficiently deliver DA to the deep part of pancreatic cancer, activate multiple cell STING pathways and immune responses, relieve hypoxia, improve immune suppression caused by hypoxia, and thus enhance the immunotherapy effect of DA.

The present invention relates to a chemically modified polysaccharide and an immunomodulatory composition comprising same. Specifically, the present invention relates to: a chemically modified immunomodulatory polysaccharide; an immunomodulatory composition comprising the chemically modified immunomodulatory polysaccharide as an active ingredient; and a pharmaceutical composition for preventing or treating cancer having immune-enhancing activity and a pharmaceutical composition for preventing or treating autoimmune diseases having immunosuppressive activity, both comprising the chemically modified immunomodulatory polysaccharide as an active ingredient, wherein the polysaccharide is modified by substituting at least one hydroxyl group with an aldehyde group, a hydroxyl group, an acetyl group, a sulfuric acid group, or a phosphoric acid group.

The invention belongs to the field of medicinal chemistry, and relates to a ketone compound as well as a preparation method, a pharmaceutical composition and application thereof. The compound is directly combined with an important immune checkpoint molecule PD-L1, inhibits expressions of PD-L1, PD-L2, FGL1 and the like in a direct and indirect manner, realizes an immune suppression checkpoint blocking effect, has anti-tumor and immune regulation effects, and has a structure as follows: R1-R8 are hydrogen, alkyl containing one to five carbons, hydroxyl, aldehyde, carboxyl, acyl and ester (-COOR, R1, R2, R3, R4, R5, R6, R7, R8 and R8 are hydrogen, alkyl containing one to five carbons, hydroxyl, aldehyde, carboxyl, acyl and ester (-COOR); wherein R is alkyl of one to five carbons) and halogen; x is oxygen, sulfur or amine. Wherein the effect of the 8-hydroxy-3-methoxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid is the most remarkable, and the application of the 8-hydroxy-3-methoxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid in the

The invention relates to the field of biological medicine, and discloses a metal supramolecular drug delivery system with dual immunomodulation.The metal supramolecular drug delivery system comprises a carrier and a BACE1 inhibitor, the carrier is formed by lipoic acid, ferric ions and bovine serum albumin through coordination self-assembly, and the surface of a shell is modified with vascular endothelial growth factors and c (RGDfK) cyclic peptide; the BACE1 inhibitor is encapsulated in the interior of the carrier and forms nanoparticles. According to the scheme, a brain delivery path and a synergistic dual immune regulation mechanism are integrated on the nanoparticles, drug delivery is performed through a meningeal lymphatic vessel path, a new brain drug delivery normal form bypassing a blood brain barrier is formed, during treatment, the immunosuppression state in a tumor can be efficiently reversed, systemic anti-tumor immunity can be powerfully activated, and meanwhile, the effect of treating the tumor is achieved. The compound has the dual targeting ability of tissue and cell levels and the tumor microenvironment responsive drug release characteristic, high accuracy and safety of treatment are ensured, the therapeutic index is remarkably improved, and the toxic and side effects are reduced.

The invention relates to the technical field of medicines, in particular to a drug targeting delivery system and application thereof in preparation of antitumor drugs. Compared with the prior art, the drug targeting delivery system provided by the invention realizes fixed-point quantitative integration of chemotherapeutic drugs through a nucleic acid solid-phase synthesis technology, and the aptamer drug can target overexpression receptor protein on the tumor surface, so that effective enrichment of the drug at the tumor part is realized. The system can synergistically induce death of immunogenic cells, and by enhancing antigen presentation and promoting maturation of dendritic cells and infiltration of effector T lymphocytes, tumor proliferation is remarkably inhibited, and an immunosuppressive tumor microenvironment is effectively relieved. The problems that existing chemotherapy-immune combined therapy is poor in targeting property, uncontrollable in medicine proportion and the like are solved, and the application prospect in antitumor medicine development is achieved.

The invention discloses an antibody conjugate for bladder perfusion and application of the antibody conjugate. According to the antibody conjugate, a PD-L1 antibody, a photosensitizer IRdye700 and a pegylation STING pathway activator PC7A are covalently linked to form a stable amido bond, and the PD-L1 antibody, the photosensitizer IRdye700 and the pegylation STING pathway activator PC7A are covalently linked to form the antibody conjugate. The invention also discloses a preparation method of the antibody conjugate and application of the antibody conjugate in bladder perfusion therapy of bladder cancer. The antibody conjugate is administered through bladder perfusion, can be specifically combined with a PD-L1 antigen on the surface of a bladder tumor cell in a targeting manner, can rapidly split a tumor cell membrane under the activation of near-infrared light, and can continuously activate the immune response of an organism through PC7A, so that the synergistic anti-cancer effect of direct killing and long-acting immunosuppression is realized.

The invention relates to Heat Shock Protein 70 (Hsp70) or a therapeutically active part thereof for use in the treatment or prevention of immune suppression, in particular immunoparalysis.

The present invention relates to an immediate-release oral pharmaceutical composition comprising Amlodipine and Ubiquinone (coenzyme Q10) for enhanced immunomodulatory activity. The formulation includes Amlodipine besylate (5 mg), Ubiquinone (coenzyme Q10) (50 mg), and pharmaceutically acceptable excipients to form a 500 mg tablet capable of rapid disintegration and drug release. The composition demonstrates superior cell-mediated and innate immune enhancement compared to standard immunostimulants, as evidenced by delayed-type hypersensitivity and carbon clearance assays. The synergistic combination not only restores immune competence in post-viral immune suppression syndrome (PVISS) and immune fatigue but also improves macrophage activation and lymphocyte response. The formulation is stable, effective, and suitable for once-daily oral administration.

The invention provides an immunotyping method and kit for endometrial cancer and application, belongs to the technical field of tumor immunology and molecular typing, and particularly relates to an immunotyping method for endometrial cancer. By detecting the expression condition of immune checkpoints in an endometrial cancer tissue sample and the infiltration proportion of immune cells, the endometrial cancer is divided into the following three immune subtypes: a low immunosuppression type, a moderate immunosuppression type and a high immunosuppression type. The immune checkpoint comprises at least one of VTCN1, PD1, CTLA4, PD-L1, P53, MSH2 and MSH6; the immune cell infiltration proportion is evaluated by detecting the proportion of CD3 positive cells. The invention provides a clinical endometrial cancer immune typing standard and a practical operation scheme, and makes up for the deficiency of the existing molecular typing in the aspect of immunotherapy guidance.

The autoimmune disease is a condition caused by an abnormal inflammatory immune response in a normal functional part of the body. Provided herein are compositions and methods for genetically engineering cells, improvements in the production of therapeutic cells, improvements in the selective expression of one or more payloads in target cells. Examples include genetically engineered immune cells, preferably immunosuppressive cells, such as Tregs, and the like, to transition the equilibrium in the active inflammation region from an inflammatory microenvironment to a more tolerant microenvironment when delivered to a patient with an autoimmune disease.

The application provides a fermented beverage for relieving fatigue and a preparation method thereof, and relates to the technical field of functional beverages, and belongs to the technical field of A23L2. The fermented beverage comprises a radix astragali fermentation extract, a platycodon grandiflorum extract, L-arginine, taurine, inositol, caffeine, nicotinamide, vitamin B6, L-lysine hydrochloride, pyrroloquinoline quinone and excipients. The radix astragali fermentation extract can improve ATP generation efficiency, reduce post-exercise lactic acid accumulation, reduce the damage of oxidative stress to muscle and nerve cells, and reduce immune suppression caused by fatigue; the platycodon grandiflorum extract can refresh the mind, improve the cognitive function decline caused by central fatigue, enhance capillary permeability, and promote the removal of metabolic waste. The radix astragali fermentation extract and the platycodon grandiflorum extract have excellent anti-fatigue effect. Under the combined action of various components, fatigue is relieved, energy is quickly supplemented, and physical strength is recovered.

The present invention provides biomaterials comprising an immunomodulatory molecule conjugated to a hydrogel, for example anti-CD3 antibody presenting engineered biomaterials, as well as methods of making the biomaterials. The invention provides anti-CD3 antibody presenting engineered biomaterials, that are hydrogels bound to anti-CD3 antibody. The invention provides methods of using biomaterials comprising an immunomodulatory molecule conjugated to a hydrogel, for example anti-CD3 antibody presenting engineered biomaterials, for immunomodulation, inducing immune suppression, and specific immune tolerance to prevent or reduce the risk of rejection of cellular or tissue grafts and / or the treatment of autoimmune disorders such as type 1 diabetes.

The present application relates to the technical field of fermentation, in particular to irpex lacteus and its application in the conversion of rare ginsenosides. The present application discovers and cultivates a wild irpex lacteus which can convert rare ginsenosides in panax notoginseng, further optimizes the irpex lacteus-panax notoginseng bidirectional solid fermentation process through experiments, and confirms that the process can efficiently convert common ginsenosides in panax notoginseng into rare ginsenosides; through pharmacodynamic evaluation, it is further shown that fermented panax notoginseng can significantly improve the pathological state of lupus nephritis model mice through multiple pathways such as immune regulation, inflammation inhibition and anti-kidney fibrosis, and its overall curative effect is better than that of panax notoginseng. The present application not only provides a new technical path for the deep development and value improvement of panax notoginseng, but also provides a potential candidate drug for the treatment of lupus nephritis, and embodies the wisdom of traditional Chinese medicine processing "synergistic and detoxification".