284 results about "Immunosuppression" patented technology

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 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.

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 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.

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 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.

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.

The present invention relates to the therapeutic use of non-classical human major histocompatibility complex (MHC) molecules (also known as MHC class Ib molecules) in combination with a peptide antigen for the treatment of neuromyelitis optica (NMO). More specifically, the present invention relates to recombinant polypeptides comprising a peptide antigen in combination with one or more domains of a non-classical MHC class Ib molecule. The present invention also relates to methods of producing such recombinant polypeptides, pharmaceutical compositions comprising such recombinant polypeptides, and their use in the treatment of neuromyelitis optica (NMO).

Aspects of the disclosure include methods of treating an autoimmune disease, including reducing the need for chronic immunosuppression, and for effectuating immune reset and / or producing a naive B cell repertoire in a subject in need thereof, the methods comprising administering a therapeutically effective amount of anti-CD20 yδ T cells to the subject, wherein the anti-CD20 yδ T cells express a chimeric antigen receptor (CAR) comprising a binding domain that specifically binds to CD20.

The present invention relates to a novel Latilactobacillus curvatus strain WiKim0169 having immunoenhancing efficacy, and an immunoenhancing composition comprising same. In the present invention, it was found that the Latilactobacillus curvatus strain WiKim0169, which is a novel kimchi-derived strain, significantly increases splenic NK cell activity and increases the production of inflammatory mediators, immunoglobulins, and cytokines, thereby alleviating immunosuppressive responses. In addition, it was confirmed that the Latilactobacillus curvatus strain WiKim0169 has an effect of alleviating immune dysfunction by increasing the mRNA expression levels of iNOS, COX2, TNF-α, IL-1β, IL-6, IL-2, IL-12, and IL-10 in splenic tissue and increasing the phosphorylation levels of NF-κB and IκBα. Therefore, according to the present invention, the composition comprising the Latilactobacillus curvatus strain WiKim0169, which is a novel kimchi-derived strain, as an active ingredient is expected to be usefully employed as a pharmaceutical and functional food composition for immunoenhancement.

The invention discloses nanoparticles for tumor chemotherapy and immune combined treatment as well as a preparation method and application of the nanoparticles, and belongs to the technical field of biological medicines. The nanoparticles are rHF (at) Cel nanoparticles formed by wrapping tripterine (Cel) with recombinant human heavy chain ferritin (rHF). The preparation method comprises the following steps: obtaining recombinant rHF protein, mixing and assembling Cel and rHF under specific pH and temperature conditions, and purifying to obtain the recombinant rHF protein. The nanoparticles can effectively target tumor cells and release Cel to kill tumors; meanwhile, the rHF carrier can induce polarization of tumor-related macrophages from a tumor-promoting M2 type to an anti-tumor M1 type, reduce the proportion of regulatory T cells (Treg) in a tumor microenvironment and reverse an immunosuppression microenvironment. In-vitro and in-vivo experiments prove that the rHF (at) Cel nanoparticles have a remarkable killing effect on breast cancer cells and can effectively inhibit the growth of transplanted tumors of mice.

This invention provides a hypoxia-mediated mechanism of malignant tumor formation, a treatment simulation method, and a system, relating to the field of biomathematical modeling technology. The method includes: dividing the tumor into a core region and a peripheral region, defining the core differences between the two regions in their microenvironmental composition, and forming a conceptual interaction network; establishing a state variable system centered on the number of tumor cells, constructing a mathematical model integrating tumor core-periphery heterogeneity, hypoxia-mediated processes, and immunosuppression cycles; solving the mathematical model, calculating the changes of each state variable over time under different initial conditions or intervention parameters, and outputting simulation results characterizing tumor growth and the state of the immune microenvironment; this invention, through the multi-level regulation of cell proliferation, immunosuppression cycles, and angiogenesis signals by oxygen concentration gradients, more realistically reproduces the spatial heterogeneous growth dynamics of solid tumors in vivo, and simulates the formation and maintenance mechanism of a strong immunosuppressive state in the tumor core region.

The present disclosure relates to the use of compound (I) and any of its salts for the treatment of a neoplasm characterized by high expression of toll-like receptor 4 (TLR4) in the tumor or its microenvironment, associated with at least one of the pathophysiological complications including immunosuppression, angiogenesis, fibrosis, or metastasis.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

Embodiments described herein relate to restorative solutions for segmental peripheral nerve (PN) defects using allografted PNs for stimulating PN repair. More specifically, embodiments described herein provide for localized immunosuppression (LIS) surrounding PN allografts as an alternative to systemically suppressing a patient's entire immune system. Methods include localized release of immunosuppressive (ISV) agents are contemplated in one embodiment. Methods also include localized application of immunosuppressive (ISV) regulatory T-cells (Tregs) and / or mesenchymal stomal cells in other embodiments. Hydrogel carrier materials are also described herein.

Disclosed herein are methods of treating a subject having diabetes mellitus with a population of cells expressing ISL1 and one or more immunosuppressive agents, such as anti-thymosin binding moieties.

The present disclosure features methods for treating neutralizing antibodies that reduce the efficacy of soluble alkaline phosphatase therapy (e.g., asfoenzyme alpha), which is an enzyme replacement therapy, such as for the treatment of bone mineralization disorders, e.g., hypophosphoesterase (HPP). The methods include diagnosing the subject for the presence of a neutralizing antibody that affects the efficacy of the treatment, administering a treatment suitable for reducing the deleterious effects of the neutralizing antibody, and continuing an alkaline phosphatase treatment.

The application discloses a biomaterial related to DCLK1 and application of DCLK1 in reversing an immunosuppressive microenvironment after EGFR-TKI drug resistance of lung adenocarcinoma, and belongs to the technical field of biotechnology.The biomaterial is an RNA molecule for inhibiting or reducing or down-regulating expression of a coding gene of a protein, or an RNA molecule for inhibiting or reducing or down-regulating activity or content of the protein, or an RNA molecule for knocking out a coding gene of the protein, or a coding gene, an expression cassette and the like related to the foregoing RNA molecule.The application shows through experiments that targeting DCLK1 can inhibit a GAS6 / AXL pathway, and down-regulate expression of PD-L1 and IDO1, thereby recovering T cell infiltration and proliferation capacity, reversing an immunosuppressive microenvironment after drug resistance, and indirectly suppressing progression of lung adenocarcinoma with three generations of EGFR-TKI drug resistance.