90 results about "Cytokine secretion" patented technology

Provided is a genetically engineered cell, which expresses a co-receptor and a membrane surface cytokine. The co-receptor contains a KIR extracellular domain, a transmembrane region and an intracellular region. When the co-receptor and the membrane surface cytokine are co-expressed in an immune cell, the cytokine secretion level, proliferation level and killing ability for a target cell of the immune cell can be further improved.

The present disclosure provides a method for preparing natural killer (NK) cells with increased secretion of cytokines and increased cytotoxicity. The present invention uses IL-12 during transfection to generate CAR-NK cells with increased functional activities (cytotoxicity and secretion of cytokines) against tumor cells.

The invention relates to the field of biological medicine, and discloses application of a GADD34 inhibitor in preparation of a medicine for enhancing CAR-T cell tumor treatment. The invention provides an innovative strategy for inhibiting CAR-T cell depletion through targeted regulation and control of an endoplasmic reticulum stress pathway to solve the problems that in an existing CAR-T therapy, the anti-tumor activity is reduced, and the solid tumor treatment effect is insufficient due to T cell depletion. Researches find that an IRE1-XBP1 pathway is used as a core signal axis of endoplasmic reticulum stress, and excessive activation of the IRE1-XBP1 pathway can drive CAR-T cell depletion related phenotypes (such as PD-1 / LAG-3 up regulation and cytokine secretion reduction). Screening experiments show that inhibiting the upstream regulatory factor GADD34 of the IRE1 not only can effectively reduce the IRE1-XBP1 signal intensity, but also can cooperatively relieve the endoplasmic reticulum stress pressure by regulating protein translation recovery, so that the CAR-T cell steady state is more comprehensively maintained. Therefore, the GADD34 inhibitor can provide a new way for enhancing CAR-T cell tumor treatment.

The invention discloses a nuclear targeting peptide modified DNA nano-particle based on a microfluidic technology and a preparation method and application thereof, and relates to the technical field of biological medicine, a poly (beta-amino ester) cationic polymer is used as a gene delivery carrier, the gene delivery carrier comprises a microtubule related sequence MTAS and a nuclear localization signal NLS oligopeptide, the gene delivery carrier and the plasmid DNA carrying the target gene are mixed to prepare nano-particles, and the plasmid DNA carrying the target gene is uniformly dispersed in the nano-particles by adopting a microfluidic mixing process; the nuclear targeting peptide modified DNA nano-particle is ingenious in structural design, the mixing uniformity of a nano-carrier and plasmid DNA is improved by adopting a micro-fluidic mixing process, the performance of the nano-particle is further improved by optimizing dialysis conditions, potential cytotoxicity and adverse effects are reduced, and the nuclear targeting peptide modified DNA nano-particle is suitable for large-scale production. And after transduction of non-activated T cells, strong tumor killing ability and cytokine secretion can be generated.

The application provides an active exosome stent coating, a vascular stent and a preparation method and application, and belongs to the technical field of biomedical intervention instruments. The active exosome stent coating of the application adopts stem cell-derived myocardial cell active exosomes which are strengthened by active components of traditional Chinese medicine. Compared with commercial myocardial cells, the stem cell-derived myocardial cells have more significant effects of promoting blood vessels and tissue repair and regeneration, and stronger cytokine secretion capacity. The preparation method of the active exosome stent coating of the application adjusts the introduction sequence and premixing mode of active components such as exosomes and drugs, and enhances the homogeneity and stability. The vascular stent prepared by using the active exosome stent coating of the application has reasonable sequential release kinetics design, can realize precise targeted regulation on human coronary artery smooth muscle cells (HCASMC) in vitro, does not affect the repair potential of endothelial cells, and solves the contradiction between traditional stents in terms of "anti-proliferation and promotion of healing".

A series of 1, 3, 5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1, 3, 5-triazine compounds as promising antitumor agents.

The invention discloses shRNA (short hairpin Ribonucleic Acid) targeting Zeb2, a recombinant vector, a cell and application of the shRNA in preparation of drugs for enhancing anti-tumor immune response, and belongs to the technical field of research and development of anti-tumor drugs. Experiments prove that the shRNA targeting Zeb2 can reduce the proportion of T cells (Tex, PD1 + Tim3 +), increase the proportion of depleted precursor T cells (Tpex, Ly108 + Tim3-), improve the secretion ability of Granzyme B and TNF-alpha cytokines of CD8 + T cells in tumor tissues, significantly inhibit the tumor growth of skin melanoma mice, increase the infiltration quantity of CD8 + T lymphocytes in the tumor tissues and the anti-tumor ability of the CD8 + T cells, and can be used for preparing anti-tumor drugs for treating skin melanoma. The polypeptide has the potential of being used for preparing drugs for enhancing anti-tumor immune response.

The invention provides application of an arsenene nano preparation and / or beta-elemene in preparation of a product for treating brain tumors, and belongs to the technical field of biology. The arsenene nano preparation and / or beta-elemene are / is applied to brain glioma and lung cancer brain metastatic tumor model mice, so that tumor cells can be effectively killed, tumor metastasis can be inhibited, in-vivo immune response can be activated, maturation of dendritic cells can be promoted, NK cells and CD8 + T cells can be effectively activated, and the secretion amount of tumor suppression cell factors can be increased. Meanwhile, the beta-elemene effectively reduces cardiotoxicity caused by accumulation of the arsenene nano preparation in vivo.

The invention provides a human FGFR3 (Fibroblast Growth Factor Receptor 3) antigen expression recombinant yeast vaccine as well as a construction method and application thereof. A specific primer is designed to amplify an FGFR3 gene, a pEGKT316-FGFR3 recombinant plasmid is constructed, a saccharomyces cerevisiae YEF473A strain is transformed, and the vaccine is prepared through induced expression and thermal inactivation. The vaccine can effectively activate DC cell maturation (CD80 + cell proportion reaches 78.7%) and promote Th1 type cell factor secretion (IL-12p70 reaches 5889pg / mL), and shows a remarkable tumor inhibition effect (plt; 0.05), and a novel specific treatment means is provided for postoperative immunotherapy of bladder cancer.

T lymphocytes play a key role in the immune response and their functions are intimately linked to metabolic programs. During immune responses, T cells undergo a metabolic reprogramming notably characterized by an increased aerobic glycolysis. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), we demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Conversely, Foxk1 overexpression in T cells enhanced their effector functions in a TCR-dependent manner. In CD8+ T cells, this effect also results into enhanced cancer cell killing capacity in vitro, and improved tumor rejection in vivo. Altogether, these results indicated that Foxk1 is a major regulator of T cell metabolism and thus, of T cell effector functions. Thus, the present invention relates to host immune cells engineered to overexpress a Foxk1 polypeptide and their use of the treatment of cancer.

This document relates to methods and materials for modulating (e.g., reducing) T cell activation (e.g., T cell proliferation, T cell effector functions, and / or cytokine secretion) using a TRAILshort polypeptide, a variant TRAILshort polypeptide, or a TRAILshort fusion polypeptide. For example, a TRAILshort polypeptide, a variant TRAILshort polypeptide, or a TRAILshort fusion polypeptide can be administered to a mammal in need thereof, e.g., a human with an autoimmune disorder, graft versus host disease, lichen planus or other disorder characterized by excessive T cell activation, to reduce excessive T cell activation (e.g., excessive T cell proliferation, excessive T cell effector functions, and / or excessive cytokine secretion).

The invention discloses an NK cell culture solution and culture and application of NK cells, the NK cell culture solution comprises an activation culture solution and an amplification culture solution, the activation culture solution and the amplification culture solution respectively contain a basal culture medium and respective corresponding cell factors, and the activation culture solution also contains calycosin with the final concentration of 0.1-10 [mu] g / mL and formononetin with the final concentration of 1-20 [mu] g / mL; the amplification culture solution also contains astragaloside IV and soyasaponin I. The components such as calycosin, formononetin, astragaloside IV and soyasaponin I added into the NK cell culture fluid can maintain stable and lasting physiological activity of NK cells and slow down cell senescence, so that secretion of cell factors is promoted, the secretion level of the cell factors is higher, and the purposes of enhancing the persistence of cell activity and improving the killing rate of the NK cells are achieved.

This invention belongs to the field of biomedical technology, specifically relating to a method and application for preparing CAR-T cells with enhanced persistence based on the piggyBac transposon system combined with electroporation. This invention, through specific piggyBac dual plasmid ratios and electroporation conditions, can improve transfection efficiency to over 80%, and the integration site is more likely to be located in a safe genomic region, supporting long-term stable CAR expression. Furthermore, cell expansion kinetics are significantly improved, with expansion exceeding 120-fold within 15 days. The results of the examples show that CAR-T cells prepared using the method described in this invention exhibit significantly enhanced tumor cell killing ability and cytokine secretion levels in in vitro models, and are rich in memory T cell subsets (Tcm / Tem) with greater persistence and self-renewal potential. This indicates that this invention not only changes the method of gene delivery but also shapes the intrinsic properties of cells, enabling them to acquire potentially superior in vivo persistence and long-term anti-tumor capabilities.

The invention belongs to the field of antibodies, and particularly relates to a bispecific antibody and application thereof. The bispecific antibody comprises a first antigen binding region and a second antigen binding region, wherein the first antigen binding region has HLA-G binding activity; and a second antigen binding region, the second antigen binding region having CD3 binding activity; wherein the first antigen binding region comprises an anti-HLA-G antibody, the anti-HLA-G antibody comprises a heavy chain complementarity determining region HCDR, and the HCDR comprises at least one selected from SEQ ID NO: 1-3 or an amino acid sequence in a conservative modification form of the at least one selected from SEQ ID NO: 1-3. The bispecific antibody can be combined with CD3 and HLA-G so as to promote T cell activation, proliferation and cytokine secretion and effectively promote PBMC to kill tumor cells, and the bispecific antibody has good anti-cancer activity; and the bispecific antibody has low binding activity with T cells and high binding activity with tumor cells, and has good clinical application value and drug development value.

This invention proposes an anti-CD3 antibody or its antigen-binding fragment and its applications. It comprises: heavy chain variable region CDRs and light chain variable region CDRs; wherein the heavy chain variable region CDRs have an amino acid sequence as shown in any one of SEQ ID NO: 1-3, 7-8, and 74-86 or a conserved modified form thereof; and / or the light chain variable region CDRs have an amino acid sequence as shown in any one of SEQ ID NO: 4-6, 9, and 87-92 or a conserved modified form thereof. The anti-CD3 antibody or its antigen-binding fragment of this invention can bind to human CD3 protein and can reduce the production of pro-inflammatory cytokines. Bispecific antibodies constructed using this antibody exhibit high PBMC-based tumor-killing activity and weak pro-inflammatory cytokine secretion-promoting properties. Therefore, pharmaceutical compositions prepared using this anti-CD3 antibody or its antigen-binding fragment or its multispecific antibody have better safety and high clinical application and drug development value.

This invention belongs to the field of biomedical technology, specifically relating to the application of a functional lipid in the preparation of drugs for treating systemic lupus erythematosus (SLE). Specifically, the functional lipid MLnM exhibits significant therapeutic effects in a pristane-induced SLE mouse model, effectively alleviating SLE-related clinical symptoms, improving intestinal barrier function, reducing oxidative stress levels, regulating the balance of inflammatory cytokine secretion, and reducing systemic inflammatory responses by inhibiting the expression of immune cell migration-related genes. The discovery of MLnM provides a new direction for the treatment of SLE and other autoimmune diseases.

The invention provides a tumor infiltration capacity enhanced TIL and a preparation method and application thereof, and belongs to the technical field of cells. The tumor infiltration capacity enhanced TIL provided by the invention is a TIL which enables the expression of the DGKZ gene to be reduced or the function to be eliminated, and has enhanced tumor infiltration capacity compared with the TIL without the DGKZ gene knockout. The tumor infiltration ability enhanced TIL provided by the invention is higher in survival rate in a depletion induction experiment, and shows depletion antagonism characteristics; experiments for performing stimulation culture on the TIL cells by using PMA show that the cytokine secretion ability is remarkably enhanced compared with that of wild TIL cells. A mouse in-vivo experiment shows that compared with a wild TIL, the DGKZ-edited cervical cancer-derived TIL cell has the advantages that the in-vivo tumor infiltration capacity and retention time are more lasting, the tumor killing capacity is higher, a better treatment effect can be achieved, and the DGKZ-edited cervical cancer-derived TIL cell has an important application value in tumor treatment.

The application discloses a gel preparation preparation method for improving cervical HPV infection and establishing a preventive barrier, relates to the technical field of gel preparation, and aims to solve the technical problems that the existing treatment methods are mostly focused on treating infected patients, and there are obvious deficiencies in the prevention of HPV infection, especially in establishing an effective preventive barrier in uninfected people, including: a crushing mechanism, which is mainly used for crushing raw materials, the crushing mechanism comprises a cabinet body, a cabinet door is arranged on one side of the cabinet body, a crushing barrel is arranged in the cabinet door, and a rotating motor matched with the crushing barrel is arranged on the cabinet door; a reverse osmosis mechanism, which is mainly used for controlling the osmotic pressure of the gel. The application has the advantages of activating local immune cells of the cervix, promoting cytokine secretion, enhancing the immune clearance ability of the body to HPV virus, providing long-acting preventive protection for the cervix, and reducing the risk of HPV infection.

The present application provides chemical compounds useful, for example, in inhibiting gasdermin pore formation in a CA cell, inhibiting inflammasome-mediated death of a cell (pyroptosis); inhibiting cytokine secretion from a cell, inhibiting an inflammatory caspase in a cell, and / or covalently reacting with a cysteine of a gasdermin protein in a cell. These compounds are also useful in treating or preventing diseases or conditions in which inflammasome activation is implicated in pathogenesis. One example of such disease or condition is sepsis.

A cell expressing a fusion protein and its applications. This cell possesses enhanced capabilities, such as cell proliferation, cytokine secretion, and tumor cell killing.

The present application relates to the application of food and composition in the preparation of functional food and dairy products. The food comprises a composition, which is composed of epigallocatechin gallate, ginseng powder and polydextrose; the mass ratio of the epigallocatechin gallate, the ginseng powder and the polydextrose is 1:(0.62-10):(0.6-46.16); the mass percentage of ginsenosides in the ginseng powder is 8% or more; the purity of the polydextrose solid is 90% or more; and the purity of the epigallocatechin gallate is 94% or more. In addition, the present application also provides the application of the above-mentioned composition in the preparation of functional food and dairy products. In the food provided by the present application, the components can effectively inhibit the M1 polarization of macrophages, promote the M2 polarization of macrophages, reduce the secretion level of pro-inflammatory cytokines, inhibit the inflammatory response, and realize the rapid improvement of the immune response ability of the body through synergistic effect at the cellular level.

The invention belongs to the field of biological medicine, and discloses a preparation method and application of CEP20 knockout type TIL for enhancing tumor microenvironment adaptability, CEP20 genes in TIL are knocked out in a targeted mode through the CRISPR / Cas9 technology, the specific method comprises the steps that tumor tissue is obtained, TIL is subjected to isolated culture, gRNA and Cas9 nuclease form an RNP compound, CEP20 gene knockout is achieved through electrotransduction, and the knockout efficiency can reach 61%; and carrying out recovery culture and rapid amplification to obtain the CEP20 knockout type TIL. Experiments prove that the CEP20 knockout type TIL does not influence cell proliferation and secretion of cell factors (TNF-alpha and IFN-gamma) in vitro, and in a cervical cancer PDX mouse model, the anti-tumor capacity of the CEP20 knockout type TIL is remarkably higher than that of unmodified TIL. By relieving negative regulation of CEP20, adaptability of TIL in a tumor microenvironment is enhanced, a new strategy is provided for immunotherapy of solid tumors (such as cervical cancer and malignant melanoma), and the TIL can be used for preparing drugs for treating solid tumors.

Provided herein are chimeric antigen receptors, comprising an extracellular domain capable of binding to an antigen, an Fc region, a flexible linker, a transmembrane domain, and may further comprise at least one intracellular domain that is designed to increase the anti-tumor activities of granulocytes, macrophages, and dendritic cells by increasing their phagocytosis and / or proinflammatory cytokines secretion and / or antigen presentation. Provided herein are vectors and nucleic acid molecules encoding any of the chimeric antigen receptors described herein. Provided herein are methods to genetically engineer granulocyte-macrophage progenitors (GMPs) to express the chimeric antigen receptors described herein. The CAR-Fc-GMPs may be induced to differentiate into macrophages or granulocytes. Provided herein are macrophages and granulocytes that express a CAR-Fc prepared by any of the methods described herein. Provided herein is an immunotherapy method for treating a subject having cancer with GMPs or macrophages or granulocytes that express the chimeric antigen receptors described herein.

The present disclosure relates to engineered bacteria, compositions and methods for immune modulation, specifically Bacteroides ovatus strains locked in a defined orientation at a genomic locus undergoing phase variation. The resulting "ON" and "OFF" mutants showed distinct immunomodulatory effects in vitro and in vivo, including differential cytokine secretion, regulatory T cell induction, and antitumor activity. These engineered strains offer a novel platform for modulating immune responses in cancer, autoimmune, and inflammatory diseases.

The invention discloses a preparation method of a gel preparation for improving cervical HPV infection and establishing a prevention barrier, relates to the technical field of preparation of gel preparations, and aims to solve the problems that most of existing treatment methods focus on treatment of infected patients, and the existing treatment methods have a poor treatment effect on prevention of HPV infection, especially establishment of an effective prevention barrier in uninfected people. The raw material crushing device comprises a crushing mechanism which is mainly used for crushing raw materials, the crushing mechanism comprises a cabinet body, a cabinet door is arranged on one side of the cabinet body, a crushing barrel is arranged in the cabinet door, and a rotating motor matched with the crushing barrel to work is arranged on the cabinet door; and the reverse osmosis mechanism is mainly used for controlling the gel osmotic pressure. The invention has the advantages of activating local immune cells of the cervix uteri, promoting the secretion of cell factors, enhancing the immune clearance ability of the body to the HPV virus, providing long-acting prevention and protection for the cervix uteri, and reducing the HPV infection risk.

The invention provides a bispecific antibody targeting PVRIG and PDL1 and an application of the bispecific antibody. The bispecific antibody comprises a first antigen binding region and a second antigen binding region, wherein the first antigen binding region has PVRIG molecular binding activity; and a second antigen binding region, wherein the second antigen binding region has PDL1 molecule binding activity; wherein the first antigen binding region is connected with the second antigen binding region. The anti-PVRIG-PDL1 bispecific antibody prepared by the invention has high affinity, can be efficiently combined with human PVRIG and PDL1 proteins, effectively blocks the combination of the PVRIG and CD112 and the combination of the PDL1 and PD1, contributes to enhancing the killing ability of human peripheral blood mononuclear cells (PBMC) to tumor cells, and improves the function of secreting cytokines by CD8T cells.

Methods of reducing T cell activation including co-culturing with T cells, term amniotic fluid mesenchymal stem cells (TAF-MSCs) isolated from term human amniotic fluid. Other aspects relate to methods of inhibiting macrophage polarization toward the M1 pro-inflammatory phenotype including co-culturing with macrophages TAF-MSCs isolated from term human amniotic fluid. Other aspects relate to methods of inhibiting cytokine secretion from activated Peripheral Blood Mononuclear Cell (PBMC) including co-culturing with the PBMC tissue-typed TAF-MSCs isolated from human amniotic fluid. Other aspects relate to methods of differentiating TAF-MSC including: obtaining TAF-MSC cells from term amniotic fluid, plating the TAF-MSC cells in limiting dilution to obtain expanded colonies from single cells, and transferring the cells to a differentiation media that contains one or more factor to differentiate the TAF-MSC cells.

The present invention discloses a recombinant type VII collagen protein, Pro.C7, whose amino acid sequence is shown in any one of SEQ ID NOs. 1-8. Also disclosed are its encoding gene, expression vector, host bacteria, preparation method, and application. The present invention designs recombinant human type VII collagen based on a partial sequence of human type VII collagen. The protein is expressed in prokaryotes, and the expression system is mature. The purified protein has been experimentally verified to be non-cytotoxic. By organizing laminin, it promotes fibroblast migration and cytokine secretion, participates in skin damage and repair, and can be used as a biomaterial in cosmetic products, among other applications.

The present disclosure provides a method for preparing natural killer (NK) cells with increased secretion of cytokines and increased cytotoxicity. The present invention uses IL-12 during transfection to generate CAR-NK cells with increased functional activities (cytotoxicity and secretion of cytokines) against tumor cells.

The invention belongs to the technical field of biological medicine, and particularly relates to application of pseudo-ginseng carbon quantum dots in preparation of a medicine for treating renal ischemia-reperfusion injury, the carbon quantum dots are synthesized by taking pseudo-ginseng as a raw material through a hydrothermal method, and the pseudo-ginseng carbon quantum dots have the antioxidant enzyme activity property, can effectively relieve cell oxidative stress and inhibit secretion of proinflammatory cytokines, and can be used for preparing a medicine for treating renal ischemia-reperfusion injury. The pseudo-ginseng carbon quantum dots specifically gather in the damaged kidney, so that the renal ischemia reperfusion injury of the mouse is obviously relieved; the pseudo-ginseng carbon quantum dots can relieve kidney injury through the following ways: reducing abundance of escherichia coli-shigella, reducing the level of indol sulfate in the kidney, regulating tryptophan-indole metabolism, regulating an AHR-Raf-ERK signal channel, down-regulating the levels of TNF-alpha and malonaldehyde, and regulating the level of glutathione. A catalytic mechanism and a multi-omics regulatory pathway of the pseudo-ginseng carbon quantum dots in renal ischemia reperfusion injury are disclosed, and experimental evidence is provided for'intestinal tract-kidney axis' in kidney disease treatment.