496 results about "Immunosuppression" patented technology

The invention belongs to the cross technical field of nanomedicine, tumor treatment and immunotherapy, and particularly provides tumor mitochondria-targeted copper death selective induction nanoparticles, which are prepared by the following preparation method: S1, specifically coupling TPY and MHI through condensation reaction to obtain MTPY; s2, MTPY and copper ions are subjected to complexation, and an MTPY-Cu complex is obtained; and S3, the MTPY-Cu complex and albumin are subjected to self-assembly, and the MTPY-Cu-coated Alb nanoparticles are formed. The dosage of copper is only 1 / 1000 of that of free Cu < 2 + >, and equivalent immune regulation and killing effects can be achieved; primary tumors and distant tumor focuses can be inhibited, and lung metastasis is reduced; immune memory can be induced, and relapse can be prevented; the traditional Chinese medicine composition is combined with cis-platinum to remarkably enhance the curative effect and reverse the induced immunosuppression; the invention has the advantages of high biological safety and no obvious liver and kidney toxicity or hemolytic reaction.

The invention relates to the technical field of microorganisms, and discloses a lactobacillus delbrueckii subsp. Bulgaricus XJFY201503 and an application thereof in improving an immune function, the lactobacillus delbrueckii subsp. Bulgaricus XJFY201503 is preserved in the China General Microbiological Culture Collection Center (CGMCC), the preservation number is CGMCC NO.30047, and the preservation time is March 18, 2024. The lactobacillus delbrueckii subsp. Bulgaricus XJFY201503 can be used for directly improving the immune function of an immunosuppressive mouse by protecting and maintaining normal physiological structures of central and peripheral immune organs and promoting secretion of serum cytokines and immune globulins; and the immune function of the mouse can be indirectly promoted by relieving intestinal inflammation reaction.

The invention discloses a function-enhanced mesenchymal stem cell preparation obtained by utilizing arthritis effusion and hypoxia pretreatment of mesenchymal stem cells as well as a preparation method and application of the function-enhanced mesenchymal stem cell preparation, and relates to the technical field of biological medicines. The preparation method of the function-enhanced mesenchymal stem cell preparation obtained by utilizing arthritis effusion and hypoxia pretreatment of mesenchymal stem cells comprises the following steps: S1, obtaining mesenchymal stem cells and performing hypoxia amplification passage; s2, pretreatment of arthritis effusion; S3, pre-stimulation of the arthritis effusion of the mesenchymal stem cells to obtain function-enhanced mesenchymal stem cells; s4, index detection and screening; s5, preparing a function-enhanced mesenchymal stem cell preparation; optimized low-oxygen pretreatment is adopted, so that the cell activity is improved; the mesenchymal stem cells subjected to joint pretreatment of arthritis effusion and hypoxia enhance expression and secretion of anti-inflammatory factors and immunomodulatory molecules in the cells; the pre-stimulated mesenchymal stem cells show a stronger immunosuppression function in vitro.

The present invention relates to chimeric antigen receptors (CAR) against multiple but not all human leukocyte antigen (HLA-G) isoforms. More specifically, the invention concerns CARs that are specific for HLA-G β2M-free or β2M-associated immunosuppressive isoforms respectively.

The invention relates to the technical field of medicines, in particular to a composite nano vaccine and application thereof. The composite nano vaccine is prepared by coupling a natural compound with endoplasmic reticulum stress induction capability on the surface of Ga-MOF nano particles. The composite nano vaccine can significantly enhance the anti-tumor effect through a ferroptosis mechanism, an endoplasmic reticulum stress and immunogenic cell death mechanism and a cryoablation technology synergistic effect mechanism, reverses an immunosuppressed tumor microenvironment, inhibits the growth of primary tumors and distant metastatic tumors, and has a good anti-tumor effect. A brand new strategy is provided for comprehensive treatment of tumors, and the application prospect is wide.

An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

The invention belongs to the field of biological medicine and ultrasonic medicine, and provides a barium titanate (BTO) piezoelectric material-based ultrasonic responsive targeting nano system (BTO at BAL), which is used for matrix microenvironment remodeling and immunopotentiation of compact tumors such as pancreatic cancer and the like. According to the nanoparticles, oleic acid modified BTO is taken as a core, ROS responsive prodrug molecules containing a small molecule PD-L1 inhibitor BMS1166 and a nitric oxide donor (Arg) 9 are loaded on the surface, and specific targeting on pancreatic cancer cells is realized by combining a targeting peptide LFC131. Under ultrasonic excitation, BTO generates reactive oxygen species (ROS), on one hand, (Arg) 9 is oxidized to release NO, tumor matrix is degraded, tumor hardness is reduced, drug delivery efficiency is improved, and meanwhile, ROS and NO synergistically enhance tumor immunogenicity; on the other hand, the ROS breaks a thioketal bond to release BMS1166, PD-L1 expression is down-regulated, and immunosuppression is reversed. According to the present invention, the significant tumor inhibition and immune activation effects are represented in the animal model, and the clinical transformation potential is provided.

The present application relates to a kind of pH / H2O2 dual-response drug-loaded hydrogel and its preparation method and application, by ε-polylysine derivative as antitumor active ingredient, with oxidized dextran through Schiff base reaction crosslinking rapid gelation. While using 2-formylphenyl boronic acid covalently package CD73 small molecule inhibitor APCP. ε-polylysine derivative has oncolytic activity, can induce ICD and promote the infiltration of immune cells in tumor cells. CD73 small molecule inhibitor APCP can block extracellular CD39-CD73-adenosine pathway, reduce the level of immunosuppressive metabolite adenosine in tumor tissue, so as to activate the infiltrated immune cells, restore its anti-tumor function. The hydrogel of ε-polylysine derivative and APCP co-delivery synergistically inhibits the effect of tumor growth, and its curative effect is greater than the treatment effect of single drug, and is superior to positive control drug oxaliplatin (OXA). The pH / H2O2 dual-response hydrogel is rapidly gelled, and has good biological safety under mild reaction conditions.

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

Embodiments of the present invention include methods of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue. Electrolysis has been used with electroporation (destabilization of the lipid bilayer via an applied electric potential) to increase cell death areas. However, the regulated increase of pH through only the cathode electrode has been ignored as a possible method to alleviate TME acidosis, which could provide substantial immunotherapeutic benefits. Here, ex vivo modeling shows that CERs can intentionally elevate pH to an anti-tumor level and that increased alkalinity promotes activation of naïve macrophages. Embodiments of the invention include pairing CER treatment protocols with existing electric field-based cancer therapies or use as a stand-alone therapy.

The invention discloses an immune homeostasis supporting agent based on mushroom active ingredients and fungal polysaccharides, and relates to the technical field of biological medicine and functional foods.The method comprises the following steps that a pleurotus citrinopileatus homeostasis adjusting extracting solution is prepared, specifically, pleurotus citrinopileatus sporocarp powder is extracted with water at the temperature of 80-100 DEG C according to the material-liquid ratio of 1 g: 35-45 mL, and a pleurotus citrinopileatus homeostasis adjusting extracting solution is obtained; the leaching time is 30-60 minutes, so as to obtain pleurotus citrinopileatus leaching liquor; the pleurotus citrinopileatus leach liquor is sequentially subjected to vacuum concentration and decoloration treatment, a pleurotus citrinopileatus steady-state regulation extracting solution with the concentration being 0.5-2 g / mL is obtained, and the pleurotus citrinopileatus steady-state regulation extracting solution shows the two-way regulation characteristic in an experimental model, so that the immunologic function index in the immunosuppression state can be improved, the excessive immune response can be relieved, and the immunologic function index of the pleurotus citrinopileatus can be improved. Therefore, the immune system is guided and maintained in a balanced and stable optimal state.

The invention discloses an application of silibinin in enhancing the immunomodulatory function of stem cells, and relates to the technical field of biological medicines. The silybin is applied to the composition for enhancing the immunoregulation function of the stem cells, the composition comprises the silybin and umbilical cord-derived mesenchymal stem cells, and the immunoregulation function of UC-MSCs is enhanced by adjusting the interaction of ICOS / ICOSL axes based on the combined action of the silybin and the umbilical cord-derived mesenchymal stem cells. The silybin disclosed by the invention is competitively combined with the ICOS, so that the interaction of the ICOS / ICOSL is blocked, and the immune regulation function of the umbilical cord-derived mesenchymal stem cells is remarkably enhanced; therefore, the UC-MSCs show a stronger immunosuppression effect in both in-vitro and in-vivo experiments; silybin not only acts on an ICOS / ICOSL axis, but also inhibits secretion of inflammatory factors through a PI3K / AKT signal channel, so that a multi-mechanism synergistic treatment effect is achieved.

The application discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

The application belongs to the technical field of nanomedicine, tumor treatment and immunotherapy, and specifically provides a copper death selective induction nanoparticle targeting tumor mitochondria, which is prepared by the following preparation method: S1, TPY is specifically coupled with MHI through a condensation reaction to obtain MTPY; S2, MTPY is complexed with copper ions to obtain an MTPY-Cu complex; and S3, the MTPY-Cu complex is self-assembled with albumin to form an MTPY-Cu@Alb nanoparticle. The copper dose of the application is only 1 / 1000 of that of free Cu 2+ , and the equivalent immune regulation and killing effects can be achieved; the primary tumor and distant tumor foci can be inhibited, and lung metastasis can be reduced; and the application can induce immune memory and prevent recurrence; the application is combined with cisplatin to significantly enhance the therapeutic effect and reverse the induced immunosuppression; and the application has high biological safety, and has no obvious hepatorenal toxicity or hemolytic reaction.

Methods are provided for targeting cells for depletion, including without limitation tumor cells such as solid tumor cells, in a regimen comprising contacting the tumor and immune effector cells with an effective dose of an anti-MSDC agent that reduces the abundance, immunosuppressive activity, or tumor recruitment of CXCR2+ granulocytic-myeloid derived suppressor cells, for example, an inhibitor of CXCR2; in combination with an effective dose of an inhibitor of CD47 / SIRPα signaling.

The invention belongs to the technical field of gene engineering and protein engineering, and particularly relates to a fully human antagonistic antibody taking a lactylated STAT6 protein as a target spot and application of the fully human antagonistic antibody. According to the present invention, the completely humanized antagonistic antibody using the lactylated STAT6 protein as the target spot is screened from the human scFv phage antibody library, the amino acid sequence of the completely humanized antagonistic antibody is represented by SEQ ID NO: 1, and the completely humanized antagonistic antibody has the specificity of the targeted lactylated STAT6 protein, and has the application prospect in preparation of the product for diagnosis, treatment or alleviation of sepsis immunosuppression.

The application discloses a kind of composition with immunoregulation and anti-aging function and preparation method thereof, and core component is marine collagen peptide, fusion polypeptide CPF-1, targeting senescent cell monoclonal antibody mAb Senolix, five gallate acyl glucose (PGG) and Hericium erinaceus polysaccharide.Fusion polypeptide CPF-1 is designed by domain fusion strategy, with collagen binding, immune activation and antibacterial function;Monoclonal antibody mAb Senolix targets the surface antigen p16^(INK4a) of senescent cell, and removes senescent cell by ADCC effect.The composition significantly improves immune cell activity, promotes collagen synthesis and reduces chronic inflammation through the synergistic effect of multiple components, and shows excellent immunoregulation and anti-aging effect in in vitro cell model and immunosuppressed mouse model, and can be used for developing immune enhancer, anti-aging drug or functional food.

The application discloses a kind of hardness correlation liver cancer lung premetastatic niche mouse model construction method, it includes the following steps: (1) in vitro enrichment respectively on the low hardness substrate of hardness 6kPa and the high hardness substrate of hardness 16kPa, the condition culture supernatant of mouse liver cancer cell Hepa1-6 that is cultured and grows, respectively named mL-CM and mH-CM;(2) mL-CM and mH-CM are respectively injected into two groups of mice using tail vein injection mode, every 1 day injection 1 time, until the 26th day, during continuous monitoring the recruitment of BMDCs in fresh lung tissue, while with the induction endpoint, i.e. 26th day premetastatic niche mark feature detection includes lung tissue matrix remodeling, immunosuppression, angiogenesis, vascular permeability and inflammation etc..The method has the advantages of short modeling cycle, easy operation, controllable induction condition, can comprehensively and accurately evaluate the common characteristics of liver cancer lung premetastatic niche formation etc..

The invention relates to the field of biological medicines, and discloses an application of an anti-thymocyte immune globulin preparation in liver transplantation immune induction, which comprises a use method and a dosage of anti-thymocyte immune globulin as an immune inducer in a liver transplantation recipient. Clinical cases prove that liver transplantation recipients use the anti-thymocyte immune globulin as immunosuppressive induction, so that the liver function and lymphocyte level can be quickly recovered to normal ranges, no obvious influence is caused on renal function, the occurrence rate of acute rejection reaction is reduced, the cytomegalovirus infection rate is not increased, and the anti-thymocyte immune globulin can be applied to liver transplantation recipients. Clinical application of the anti-thymocyte immune globulin in immune induction treatment of liver transplantation recipients is expanded, and the anti-thymocyte immune globulin has a great application prospect.

A vaccine for use in the prophylaxis and / or treatment of a diseaseThe present invention relates to an adenoviral vector capable of encoding a virus-like particle (VLP), said VLP displaying an inactive immune-suppressive domain (ISD). The vaccine of the invention shows an improved immune response from either of both of the response pathways initiated by CD4 T cells or CD8 T cells.

This invention belongs to the field of animal model construction technology, specifically relating to a mouse immunosuppressive model that maintains a long-term immunosuppressive state, its construction method, and its application. This invention establishes a stable immunosuppressive state model with reduced neutrophil count and no significant decrease in erythrocyte count by administering different doses of immunosuppressants (10-50 mg / kg body weight) to Balb / c mice via a combination of "reduced total dose + multiple gavage administration + satellite monitoring." The method for constructing this mouse immunosuppressive model reduces drug usage, controls neutrophil count rebound, establishes a stable model of reduced neutrophil count, and avoids deep bone marrow suppression (i.e., does not cause an uncontrollable decrease in erythrocyte or platelet count), which is beneficial for long-term experimental conduct and drug evaluation.

This application relates to the fields of chemistry and biomedicine, specifically to a tofenamic acid lipid composition, its preparation method, and its application. A tofenamic acid derivative is obtained by reacting a morpholine solution with tofenamic acid, ethyldimethylaminopropylcarbodiimide, and 4-dimethylaminopyridine, followed by purification. The morpholine in the morpholine solution is an N-alkylmorpholine compound. The tofenamic acid derivative is used to prepare tofenamic acid prodrug liposomes via ethanol injection, which are then used in combination with a STING agonist. The synergistic effect of the combined treatment stems from the dual regulation of the tumor immune microenvironment (TME), overcoming the immune escape induced by STING monotherapy. After STING agonist treatment, the intratumoral COX-2 / PGE2 axis is activated, leading to immunosuppression. The combination of tofenamic acid liposomes and a STING agonist inhibits COX-2, thus relieving this negative feedback loop.

The present application relates to a kind of water gel based on crude polysaccharide of Radix Trichosanthis and its preparation method and application.The water gel based on crude polysaccharide of Radix Trichosanthis is prepared by the following method:1) preparing crude polysaccharide of Radix Trichosanthis;2) making aldehyde group of crude polysaccharide of Radix Trichosanthis to obtain aldehyde group of crude polysaccharide of Radix Trichosanthis;And 3) aldehyde group of crude polysaccharide of Radix Trichosanthis and carboxymethyl cellulose are covalently combined to form the water gel by Schiff base reaction.The multifunctional water gel of the present application is expected to become the candidate dressing of clinical protection and treatment of cachexia wound and other immunosuppressive chronic wound.

The application provides an immune cell preparation method capable of reversing tumor microenvironment immunosuppression signals and application thereof. The method for reversing the inhibitory signals is to replace the intracellular segment of a TIGIT receptor with a 4-1BB costimulatory domain and an IL-18R and a CD3 intracellular segment, and the immune cells expressing the chimeric antigen receptor recognize CD155 in a tumor microenvironment through TIGIT, avoid loss of function or exhaustion of the immune cells, and stimulate the immune cells to exert stronger tumor killing activity.

A pro-inflammatory and vasoconstrictor and endothelin-1 (ET-1) are pathogenic molecules related to a series of cardiovascular diseases. Unlike ET-1 signaling for vasoconstriction of the main artery, we have proven herein that coronary microvessels exhibit a unique signaling mechanism for constriction (independent of PKC, CPI-17, and intracellular calcium storage). The pathophysiological level of ET-1 acts preferentially on the microvessels to exert persistent vasoconstriction by activating Rho kinase upon binding to ETAR of the ET-1 receptor. The ETAR antagonist BQ123 only blocks but cannot reverse vasoconstriction against ET-1. In contrast, ROCK inhibitors (e.g., H-1152) are effective to reverse arteriolar systole against ET-1. Thus, ROCK inhibition is a potent and specific choice for the treatment of coronary ischemic disease (abnormal vasoconstriction) associated with microvascular dysfunction due to excessive production of ET-1. The ROCK inhibitors may also be used to treat microvascular diseases associated with diabetic retinopathy as well as microvascular dysfunction caused by cancer therapy or immunosuppressive drugs. Since H-1152 can also reduce the basal tension of microvessels, a ROCK inhibitor is also a good diagnostic agent when used during angiography or by a non-invasive method.

Sesterterpenoid compounds and an extract L01 of Leucosceptrum canum, and use thereof in treatment of psoriasis are provided, belonging to the technical field of natural medicinal chemistry. The sesterterpenoid compound of the Leucosceptrum canum has a structure shown in any one of Formulas 9 to 12, which shows a highly rare backbone type, exhibits anti-inflammatory and immunosuppressive activities, and can be used in preparation of an anti-inflammatory drug and an immunosuppressive drug. A Leucosceptrum canum extract L01 having compounds 1 to 12 as characteristic ingredients, and use thereof in preparation of an anti-inflammatory drug and an immunosuppressive drug are further provided.

The present invention relates to a composition for diagnosing immunodeficiency or a method for providing information for diagnosis thereof. By using the composition and the method according to one aspect, it is possible to simply and effectively diagnose immune-deficient conditions such as immunosuppression or immune paralysis.

The present disclosure relates to a pharmaceutical composition comprising an inhalable immunosuppressive macrocyclic active ingredient for use in the prevention or treatment of a pulmonary disease or condition in a subject, wherein the pharmaceutical composition is administered to the subject by inhalation in the form of an aerosol, and wherein the aerosol is produced by nebulizing the pharmaceutical composition using a nebulizer (100), which nebulizer comprises: a) an aerosol generator (101) comprising: - a fluid reservoir (103) for holding the pharmaceutical composition or an interface configured to connect a fluid reservoir, and a vibrating membrane (110) with a plurality of apertures, which apertures are adapted to produce an aerosol comprising droplets having a mass median aerodynamic diameter (MMAD) of up to about 4.0 gm as measured with aqueous 0,9% (w / v) sodium chloride solution; b) a chamber (105) for temporarily receiving the aerosol produced by the aerosol generator (101), wherein the chamber has an internal lumen with a volume in the range of about 50 to about 150 ml; and c) a mouthpiece (40) for delivering the aerosol provided by the nebulizer (100) to the subject, wherein the mouthpiece has an exhalation filter (30).,

Compound of formula (I) able to simultaneously modulate Store Operated Calcium Entry (SOCE) and human dihydroorotate dehydrogenase (hDHODH). The disclosure also relates to compositions and uses of compounds of formula (I) for treatment of autoimmune, inflammatory, and chronic degenerative diseases, as well as neurodegenerative and multisystem inflammatory diseases associated with SOCE overactivation and DHODH pathway alterations, while avoiding immunosuppression, the main side effect of the currently available therapies.

The invention belongs to the technical field of tumor immunotherapy, and relates to an anti-Claudin18.2 single-domain antibody, a multifunctional fusion protein, a recombinant natural killer cell (CT-CAR-NK), and preparation and application thereof. Through alpaca immunization and phage display library construction and panning, the single-domain antibody VHH-C18.2-1 specifically combined with Claudin18.2 is obtained, and the amino acid sequence of the single-domain antibody VHH-C18.2-1 is SEQ ID NO: 1. The amino acid sequence of the designed fusion protein is SEQ ID NO: 3, the fusion protein sequentially comprises a VHH-C18.2-1, a flexible Linker, a TGF-beta RII extracellular domain, a CD8alpha hinge region, a CD8alpha transmembrane region, a 4-1BB intracellular domain and a CD3zeta intracellular domain from the N end to the C end, and the fusion protein has the functions of targeting, resisting TGF-beta inhibition and activating signals. The fusion protein gene transfects human peripheral blood CD56 + CD3-NK cells through lentivirus to obtain CT-CAR-NK, in-vitro verification shows that the CT-CAR-NK still keeps efficient killing in an immunosuppression environment, tumor growth can be remarkably inhibited in vivo, the lifetime can be prolonged, and a safe and efficient scheme is provided for Claudin18.2 positive solid tumor treatment.