108 results about "Cytokine storm" patented technology

The invention provides a nucleotide sequence encoding a CAR (Chimeric Antigen Receptor) and an ROBO1 CAR-NK cell expressing the CAR. The ROBO1 CAR-NK cell provided by the invention specifically killstumor cells by applying an ROBO1 antibody to the construction of a CAR-NK cell which takes an ROBO1 molecule as a target antigen. The ROBO1 CAR-NK cell can be taken as a medicament for treating tumordiseases, is used for treating tumors with high expression of the ROBO1 molecules, is free from undesirable phenomena such as cytokine storm, and provides a novel treatment method for tumors which cannot be treated with traditional surgery, chemotherapy and radiotherapy; moreover, the ROBO1 CAR-NK cell has the advantages of small toxic and side effects, high safety and better killing effect compared with an ROBO1 CAR-T cell.

The invention relates to a gene of an MLL leukemia targeted dual-specific chimeric antigen receptor and an application of the MLL leukemia targeted dual-specific chimeric antigen receptor. The dual-specific chimeric antigen receptor disclosed by the invention can be used for specifically recognizing two kinds of tumor associated antigens, i.e., CD19 and CD133 on surfaces of MLL leukemia cells. The dual-specific chimeric antigen receptor is expressed through recombining a TanCAR molecule to a virus vector and carrying out T lymphocyte series transfection, dual positive tumor cells, i.e., the CD19 and the CD133 can be specifically recognized and killed, the kill effect on non-tumor cells is relieved, and the probability of escape of tumor antigens is lowered. The MLL leukemia cells can be specifically killed by TanCAR(1linker)-Jurkat in case of a relatively low effector-target ratio, and toxic or side effects less occur in subsequent clinical use, for example cytokine storm and neurotoxicity. The dual-specific chimeric antigen receptor disclosed by the invention can be applied to the treatment of MLL leukemia and is used for clearing in-vivo tumors from patients and prolonging lifetime of the patients.

The invention relates to mesenchymal stem cell membrane-coated bionic nanoparticles with overexpressed PD-L1 molecules on the surface as well as preparation and application of the mesenchymal stem cell membrane-coated bionic nanoparticles. The mesenchymal stem cell membrane-coated bionic nanoparticle with the overexpressed PD-L1 molecules on the surface comprises a nano-core and a mesenchymal stemcell membrane wrapping the nano-core, the nano core comprises a polymer with biocompatibility, and PD-L1 molecules are overexpressed on the membrane surface of the mesenchymal stem cell membrane. Theinvention also discloses an application of the mesenchymal stem cell membrane-coated bionic nano-particle with over-expressed PD-L1 molecules on the surface in preparation of an inflammation treatment preparation. The bionic nanoparticle has a remarkable immunosuppression effect, is high in biocompatibility and simple and mature in preparation process, can be used for preparing an inflammation treatment preparation, can be effectively enriched in an inflammation part, and shows an excellent curative effect in inflammation treatment by inhibiting excessively activated immune response and cytokine storm of the inflammation part.

The present invention relates to improved methods and compositions for treating viral infections and other diseases and conditions that induce a cytokine storm. More particularly, the present invention relates to novel compositions comprising quercitin, and an anti-convulsant, such as phenytoin, in combination with mulivitamins as an anti-viral composition and methods of use thereof.

The invention provides a chimeric antigen receptor. The chimeric antigen receptor comprises an extracellular structural domain, a transmembrane structural domain and an intracellular structural domainwhich are connected in sequence, wherein the extracellular structural domain comprises an antigen recognition region and a hinge region; and one end of the intracellular structural domain, which is connected with the transmembrane structural domain, is connected with a CD3 epsilon intracellular region. The chimeric antigen receptor provided by the invention can further improve the treatment effect of B-cell leukemia lymphoma in B-cell leukemia lymphoma treatment, and reduces inflammatory cytokines generated by macrophage monocyte activation by down-regulating cytokines of the chimeric antigenreceptor, so that cytokine storm can be prevented at an early stage, and the risk of neurotoxicity can be reduced. The treatment effect of solid tumors with high mesothelin expression is further improved in mesothelin positive tumor treatment, and meanwhile, cytokine storm can be prevented in an early stage and the risk of neurotoxicity can be reduced.

The invention particularly discloses a new method for treating viral infection patients by mesenchymal stem cells. The method comprises the following steps: S1, preparing a mesenchymal stem cell preparation; S2, dividing treatment of viral infection patients into a mesenchymal stem cell treatment group and a reference treatment group; S3, treating viral infection patients in the natural control treatment group according to an original treatment scheme, and meanwhile, introducing the prepared mesenchymal stem cell preparation into the mesenchymal stem cell treatment group for combined treatment; and S4, respectively sampling and analyzing the peripheral blood mononuclear cells of the healed patient in the reference treatment group and the mesenchymal stem cell treatment group. The mesenchymal stem cell preparation is introduced into an original treatment scheme for combined treatment, so that a healed patient has a stronger immune function, the recovery capability of the healed patientis enhanced, virus replication of the healed patient is inhibited, and the influence of cytokine storm is reduced.

A tumor immune T cell detection kit and method are provided. The kit includes specific primers for detecting specific quantitative expression of immune-related target genes in human peripheral blood T cells through subjecting the target genes to PCR amplification based on SYBR-Green quantitative PCR amplification. The immune-related target genes include receptor and ligand related target genes, NK cell related target genes and key cytokine genes. Expression profiles of the immune system related target genes in the human peripheral blood T cells can be accurately and quantitatively detected by the kit and the method successfully so that targets can be provided for accurate immune treatment of tumor patients. In a treatment process, cytokine storm response to immune treatment of a patient can be detected timely, thus providing guidance for avoiding adverse reactions. States of the immune system in the treatment process and after treatment are assessed, thus providing supports for adjusting the amount of an antibody medicine used for treatment or the feedback number of modified T cells and even target adjustments. The kit and the method are comprehensive in detection, rapid, quantitative, accurate, high in sensitivity and low in cost.

The invention relates to application of IFN-lambda in preparation of a drug for treating a patient infected with a novel coronavirus. The level of the novel coronavirus in the infected patient can be effectively reduced, and the IFN-lambda shows more excellent performance in the aspects of controlling cytokine storm caused in the treatment process and relieving respiratory distress syndrome caused by the cytokine storm.

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions comprising apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do notreduce the efficacy of the CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm comprising administration of a composition comprising apoptotic cells or an apoptotic cell supernatant.

The invention relates to detection of cytokines related to cytokine storm and provides an index combination used for executing immunization therapy or prognosis detection for other diseases producingcytokine storm. The cytokine combination covers 9 indexes capable of detecting the cytokine storm and can realize high-sensitivity detection of a serum micro-sample with a solid phase chip / liquid phase chip / ELISA (enzyme linked immunosorbent assay) kit method. The cytokine combination has the characteristics of good focusing property, high accuracy and the like in the cytokine storm monitoring process, can guide diagnosis and treatment and has remarkable clinical application value.

The invention provides hydroxyprogesterone hexanoate for treating various diseases which cause the cytokine storm, such as COVID-19, infection of various virulent viruses, side effects after monoclonal antibody treatment, side effects after CAR-T treatment, inflammatory bowel diseases, pancreatitis and the like. Meanwhile, the invention also provides a method for treating the above diseases by using a corresponding medicine composition. Experimental results show that the progestational hormone hydroxyprogesterone hexanoate can effectively inhibit the cytokine storm and is expected to become an effective medicine for treating diseases such as the COVID-19 and the like.

The invention belongs to the field of medical biotechnology, and particularly relates to a genetically modified immune cell with a malignant solid tumor treating function and application thereof. The immune cell is a specific immune cell which is subjected to gene modification so as to over-express lipid metabolism-related genes. The tumor growth inhibiting capacity of the immune cell is realized by reducing accumulation of lipid droplets of the immune cell itself in a tumor microenvironment, reducing expression of tumor promotion genes / protein, and improving the phagocytotic ability, antigen presentation ability and tumor killing ability of the immune cell. The immune cell is an in-vitro NKT cell, a DC cell, a macrophage, a monocyte, a granulocyte or a T cell. Overexpression of related metabolism regulation genes enables the anti-tumor capacity of the immune cell to be improved remarkably. Compared with a chimeric antigen receptor T cell immunotherapy (CAR-T) which receives much attention currently, toxic and side effects are small, cytokine storm can not be caused, and clinical requirements can be met.

The invention discloses a blood purification adsorbent. The blood purification adsorbent is porous polyurethane aerogel. The invention also discloses a preparation method of the blood purification adsorbent, and the blood purification adsorbent is prepared by taking MDI trimer and polyethylene glycol / polypropylene glycol as raw materials through adoption of a sol-gel method and supercritical carbon dioxide drying. The invention also discloses a hemoperfutor. The porous polyurethane aerogel is used as an adsorbent in the hemoperfutor. The blood purification adsorbent provided by the invention adopts a porous polyurethane aerogel material, and has the advantages of excellent mechanical properties, controllable pore size and distribution, the high specific surface area, the large adsorption capacity and the like; and the adsorbent is wide in adsorption range, can adsorb bacterial endotoxin, tumor necrosis factors, interleukin 6 and other cytokines in blood plasma at the same time, and canbe used for treating endotoxemia, sepsis, cytokine storm and other diseases caused by severe infection.

The invention belongs to the technical field of biology, and particularly relates to an in-vitro cytokine storm model and a construction method and application thereof. The construction system of the in-vitro cytokine storm model contains a TNF-alpha factor, an IL-1[beta] factor, an IL-6 factor and vascular endothelial cells. The in-vitro cytokine storm model is formed by the body. According to the in-vitro cytokine storm model construction method, vascular endothelial cells, TNF-alpha factors, IL-1[beta] factors and IL-6 factors are incubated together. The invention discloses application of an in-vitro cytokine storm model in screening of anti-cytokine release syndrome drugs. The invention relates to an application of an in-vitro cytokine storm model in preparing and screening anti-cytokine release syndrome drugs. The in-vitro cytokine storm model disclosed by the invention is obtained by jointly treating vascular endothelial cells through three factors, namely TNF-alpha, IL-1[beta] and IL-6, the in-vitro cytokine storm model with high cell apoptosis rate and obviously reduced cell activity can be prepared, and a better basis is provided for research on inflammatory response related to multiple factors.

The invention discloses an in-vitro amplification method and an application of glioma-derived tumor infiltration lymphocytes (TIL), and belongs to the technical field of cell culture. The method comprises the following steps: pre-culturing TIL cells; and culturing and amplifying the TIL cells. According to the method, under the condition that glioma infiltrating lymphocytes are not separated, theTIL cells are directly induced and cultured, then a large number of TIL cells are amplified, the operation procedure is simple, consumed time is short, the TIL cell amplification number and cell activity can be obviously improved, and the method has a good effect of killing glioma tumor cells. In the steps of TIL cell culture and amplification, a low-concentration cytokine composite nutrient medium is adopted, so that the requirements of TIL cell culture and amplification are met, and the potential risk of cytokine storm in the subsequent treatment process is reduced.

The invention belongs to the field of biological medicine and relates to polypeptide fragment derived from intermedin (IMD; alternate name, Adrenomedullin 2, ADM2). The polypeptide fragment is specifically mature peptide IMD108-147 with the length of 40 amino acids. Researches show that intermedin precursor peptide and three kinds of sheared manure peptides can reduce cytokine storm caused by sepsis, have a protection effect on vascular endothelial barriers, can reduce tissue edema and organic damage, can effectively reduce death rate of the sepsis. The IMD108-147 related in the invention has possibility of serving as polypeptide medicine to be applied to preventing and treating clinical sepsis and has a very good application prospect.

The invention relates to the technical field of medicines, in particular to an application of GS-9620. Experiments prove that the GS-9620 can effectively inhibit replication of EV71 viruses, reduce the death rate of infected mice, improve clinical symptoms of the infected mice and relieve pathological injuries of muscles. The GS-9620, by inhibiting NK cells and macrophages, can inhibit secretion of various cytokines and reduce injury of a body caused by cytokine storm; therefore, an effect of treating hand-foot-and-mouth disease or herpangina caused by the EV71 viruses can be achieved effectively and safely.

A method for administering human umbilical cord blood mesenchymal stem cell transfusion immunotherapy to a patient for treatment of coronavirus infection. The method includes harvesting umbilical cord mesenchymal stem cells, culturing the stem cells, collecting and purifying the cultured stem cells, placing the purified stem cells into a transfusion bag, and intravenously transfusing the stem cells from the transfusion bag into the patient having the infection.

The invention relates to applications of trametinib to preparation of a drug for treating pulmonary inflammatory diseases and promotion of Tfh cell differentiation. The chemical formula is C26H23FIN5O4. The applications include an application of trametinib to promotion for Tfh cell differentiation and an application of trametinib to preparation of the drug for treating the pulmonary inflammatory diseases. The trametinib has beneficial effects as follows: cytokine storm caused by activation of T cells and mononuclear macrophages can be better inhibited, and meanwhile, Tfh differentiation, B cell maturation mediation and antibody production are promoted; and as abroad-spectrum immune regulation drug, the trametinib has an effect of promoting antibody production in the aspects of other viralpneumonia, virus infection or seedling inoculation.

The invention discloses an exosome secreted by an lncRNA gene modified cell and application, and belongs to the field of cell biology. The exosome is secreted by an HEK-293T cell strain obtained through genetic engineering, the HEK-293T cell strain stably expresses lncENAF, and the nucleotide sequence of the lncENAF is as shown in SEQ ID NO: 1. The exosome can effectively inhibit generation of lipopolysaccharide-induced macrophage cytokines, is a potential cytokine inhibitor, and provides a new direction for cytokine storm and treatment of autoimmune diseases.

The invention discloses a bifunctional fusion protein combined with coronavirus. Binding regions at two ends of the bifunctional fusion protein are respectively combined with different epitopes of a Spike protein, and the bifunctional fusion protein simultaneously has the functions of resisting SARS-CoV and SARS-CoV-2 and the function of combining ACE2. The bifunctional fusion protein combined with coronavirus has the capability of treating virus infected cells, and also has the effects of resisting viruses, reducing lung inflammation, reducing cytokine storm and treating lung injury.

The invention provides an EGFR-targeting chimeric antigen receptor. The EGFR-targeting chimeric antigen receptor comprises an antigen binding domain of an anti-EGFR antibody, wherein the antigen binding domain of the anti-EGFR antibody is expressed as EGFRscFv; and the EGFRscFv has a nucleic acid sequence as shown in SEQ ID NO: 2. The invention also provides a CAR-NK cell and a preparation methodthereof. The NK cell expresses EGFRscFv of the EGFR-targeting chimeric antigen receptor to obtain the EGFR-targeting CAR-NK cell. The invention also provides a composition, an anticancer agent and applications. The EGFR-targeting CAR-NK cell provided by the invention has specific recognition on an EGFR target of triple negative breast cancer, kills EGFR positive triple negative breast cancer cellsin a targeting manner and promotes release of cytokines. When the CAR-NK cells are used as effector cells to recognize tumors, leukocyte antigens of the CAR-NK cells do not need to match the tumors,so graft-versus-host reaction cannot be generated. The CAR-NK therapy method does not cause cytokine storm and is safer. The CAR-NK cell is wide in sources like peripheral blood mononuclear cells, induced pluripotent stem cells, umbilical cord blood, human embryonic stem cells and NK-92 cell lines.

The invention provides a universal chimeric antigen receptor-T (CAR-T) cell as well as a preparation method and application thereof. The universal CAR-T cell can recognize polypeptide GCN and GCN-autoantibody affinity peptide fusion polypeptides, and can recognize and kill different self-reactive b cells in a targeted way under the guidance and regulation of different GCN-autoantibody affinity peptide fusion polypeptide guiders. The intensity or complete closure of an in vivo immune effect of the CAR-T cell can be very conveniently controlled, so that the reduction of other risks or side effects such as cytokine storms in general CAR-T cell therapy is facilitated; the universal CAR-T cell is different from conventional CAR-T cells need to be designed with different CARs aiming at differenttargets; therefore, time and cost are greatly reduced, and the success rate is increased.

The invention belongs to the technical field of CAR-T living body CT imaging, and particularly discloses a preparation method and application of a gold nanocage. The preparation method of the gold nanocage comprises the following steps of preparing CF3COOAg mother liquor; preparing polyvinylpyrrolidone mother liquor; preparing hydrochloric acid mother liquor; preparing NaHS mother liquor, and taking the NaHS mother liquor, ethylene glycol hydrochloride mother liquor, vinylpyrrolidone mother liquor and CF3COOAg mother liquor for reacting; transferring a reaction product obtained in the previousstep into a centrifugal tube, adding an acetone solution for washing and purifying, adding water into the product for dispersing, centrifuging to remove supernate, and washing to obtain a silver nanocubic solution; and preparing the gold nanocage by adopting an electrochemical replacement method. The gold nanocage is applied to a CAR-T living CT imaging agent. The method has the following beneficial effects that a cytokine storm is not easily caused; and CAR-T can be transfected at a time through electroporation, the operation process is simple, and the CAR-T has the advantages of high contrast and high specificity through CT imaging.

The invention belongs to the field of biological medicines and discloses an alveolar macrophage-like multifunctional nanoparticle loaded with an aggregation-induced emission photothermal material anda preparation method and use of the alveolar macrophage-like multifunctional nanoparticle. The nanoparticle is obtained by taking an aggregation-induced emission photosensitive molecule 2TPE-2NDTA anda polylactic acid / glycollic acid copolymer as a co-carrier to form a core of a nano-drug and coating the 2TPE-2NDTA and the polylactic acid / glycollic acid copolymer with an alveolar macrophage membrane through a design and synthesis. The nanoparticle also has a characteristics of a photo-thermal agent and can be excited by near-infrared laser, and generated heat is used for photo-thermal killingof novel coronaviruses. Meanwhile, since the alveolar macrophage membrane on an outer layer of a nano-drug has related receptors on a surface, the nano-drug can adsorb SARS-CoV-2 and cytokines, so that a purpose of resisting a cytokine storm is achieved. The alveolar macrophage-like multifunctional nanoparticle can also solve a disadvantage and a deficiency of a poor curative effect in a traditional antiviral treatment scheme and becomes a new antiviral treatment strategy.

The invention discloses application of a stilbene glucoside compound in preparation of a medicine for preventing and / or treating coronavirus infection diseases. The medicine prepared from the stilbene glucoside compound shows an inhibition effect on the SARS-CoV 3CL protease activity and an effect of inhibiting combination of an SARS-CoV S protein and host cells ACE2. Meanwhile, the medicine also has the effects of preventing and / or relieving cytokine storm caused by coronavirus infection and preventing and / or relieving acute inflammatory injury of multiple organs caused by coronavirus infection.

The invention discloses a human-derived CD-19 chimeric antigen receptor T lymphocyte vector which is characterized by comprising a plasmid vector for coding single-chain variable region genes of CD19monoclonal antibodies, nucleosomal histone monoclonal antibodies and FNEDB monoclonal antibodies. The vector is a lentiviral vector. The invention further discloses application of the human-derived CD-19 chimeric antigen receptor T lymphocyte vector in preparation of CATR cells. The vector is used for transduction of T lymphocytes, natural killer cells and mononuclear cells, and is applied to treating tumors, preferably treating reoccurrence in malignant lymphoma drugs as well as neoplastic hematologic disorders and lymphomas which are refractory and unsuccessful in bone marrow transplantationmatching. The human-derived CD-19 chimeric antigen receptor T lymphocyte vector disclosed by the invention has the beneficial effects that the vector constructed in the invention can achieve the effects of enhancing the targeted CD19 antigen transgenic T lymphocyte specificity, overcoming the tumor microenvironment inhibited immune cellular function and controlling cytokine storm in clinic treatment.

The invention provides a T cell for expressing an immunosuppressive checkpoint receptor molecule and an application of the T cell. The immunosuppressive checkpoint receptor molecule is expressed on aT cell membrane in a chimeric manner and comprises an immunosuppressive checkpoint and an immune activation signal structural domain, wherein the immunosuppressive checkpoint is a signal peptide, an extracellular domain and a transmembrane domain of the immunosuppressive checkpoint receptor molecule; the immune activation signal structural domain comprises a combination of a CD28 intracellular segment, CD3 zeta and TLR2; and the CD28 is located at the N end of the CD3 zeta, and the TLR2 is located at the C end of the CD3 zeta. Compared with wild type T cells, the T cell disclosed by the invention has a remarkably enhanced anti-immunosuppression effect, has a stronger killing effect on tumor cells expressing immunosuppression checkpoint ligands, does not cause cytokine storm, is higher in safety, and has a wider application prospect in the field of tumor treatment.