105 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".

The invention relates to the technical field of medicines, in particular to medical application of a kedilao extract. The invention discloses the medical application of the kedilao extract for preventing, relieving and / or treating allergic asthma for the first time. The kedilao extract can reduce inflammatory cell infiltration, improve airway structure damage and improve airway wall thickening; the secretion of Th1 type cytokines is improved, the secretion of Th2 type cytokines is reduced, and the effect of obviously relieving asthma is achieved. Compared with an existing medicine for treating asthma, the kedilao extract is safer, more effective, milder and lasting, the action mechanism is multi-target and multi-effect, and the situation that a single-target medicine generates strong drug resistance is avoided. Therefore, the kdilao extract has considerable development and utilization values in the aspect of relieving and treating the allergic asthma.

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 provides a CAR-NK cell for knocking out KIR2DL5 targeting HER2 as well as a preparation method and application of the CAR-NK cell, and belongs to the technical field of genetic engineering.The CAR-NK cell is obtained by adopting a chimeric antigen receptor with HER2 as a target spot to infect an NK cell and then knocking out a KIR2DL5 gene; the chimeric antigen receptor taking the HER2 as the target spot comprises an HER2 single-chain antibody; the nucleic acid artificial sequence of the HER2 single-chain antibody is as shown in SEQ ID NO. 2. According to the application disclosed by the invention, the interaction of KIR2DL5-PVR is blocked by knocking out NK cell immune checkpoints, so that tumor immune escape is avoided, and the activity of killing tumor cells by CAR-NK cells is remarkably enhanced; according to the invention, by optimizing the nucleic acid artificial sequence of HER2, the secretion ability of CAR-NK cell factors, the tumor killing efficiency and the in-vivo inhibition effect on tumors can be improved.

The embodiment of the present invention discloses an induction culture medium, method and application for improving the viability and factor secretion ability of hair follicle-derived mesenchymal stem cells in a hypoxic environment. The induction culture medium includes a basal culture medium and an induction drug, and the induction drug includes transforming growth factor β, hepatocyte growth factor, cyclic adenosine monophosphate, triptolide, sodium hydrosulfide, lipopolysaccharide, hyaluronic acid, dexamethasone, L-glutamine and HEPES buffer. The induction culture medium provided by the present invention can promote the metabolism and energy production of hair follicle-derived mesenchymal stem cells, enhance the antioxidant capacity of cells, improve the survival rate and factor secretion ability of cells in a hypoxic environment, and solve the problems of low cell viability, slow growth, low cytokine secretion, etc. after transplanting cells into damaged tissue areas in the prior art.

The invention relates to a preparation method of a CpG ODN nano immune complex, which comprises the following steps: (1) uniformly mixing a protamine solution with a certain concentration and a CpG motif-containing oligodeoxynucleotide CpG ODN aqueous solution with a certain concentration according to a certain ratio, and carrying out electrostatic compounding assembly at room temperature to form a suspension; and (2) applying energy to the suspension to disperse / homogenize uniformly to form the suspension of the nano-composite. The nano-composite prepared by the method disclosed by the invention is controllable in particle size and controllable in surface charge. The nano particles formed under the preparation condition of an optimized proportion are uniformly dispersed, good in stability, good in resolubility after freezing, and good in long-term storage stability. The preparation method provided by the invention is simple, does not involve toxic and harmful chemical substances, and is suitable for amplification. Compared with the prior art, the preparation method provided by the invention can obviously improve the effective concentration of the effective active substance CpG ODN in the nano immune complex. The invention also relates to the nano immune complex prepared by the method and application thereof. Cell and animal experiments prove that the nano immune complex prepared by the method has good immunostimulatory activity, can stimulate the maturation of related immune cells and induce the secretion of related cytokines, can be independently used as an immunomodulator, and can also be used as an immunologic adjuvant to be combined with various antigens to be used as a vaccine preparation as a whole. The nano immune complex has good application prospects in the fields of inducing and activating immune cells to mature, releasing cytokines, resisting allergic diseases, preventing and treating microbial infectious diseases, vaccine adjuvants, resisting tumor immunotherapy and resisting Alzheimer's disease.

A cell expressing a fusion protein and a use thereof. The cell has enhanced abilities, such as cell proliferation ability, cytokine secretion ability, and tumor cell killing ability.

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.

Provided are a cell expressing a multispecific antigen binding protein and the use thereof. The cell has enhanced capabilities, such as cell proliferation, cytokine secretion, and tumor cell killing capabilities.

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.

The invention provides an autologous stem cell preparation and a preparation method thereof, and aims to improve the immunocompetence of stem cells and enhance the application potential of the stem cells in treatment. The method comprises the following steps: firstly, collecting peripheral blood from healthy adult volunteers and separating mononuclear cells; then amplifying the cells under a specific culture condition, and performing immune activation through a TLR7 / 8 agonist and an anti-CXCR4 single-domain antibody; then, evaluating the phenotype and cytokine secretion level of the stem cells after immune activation through a flow cytometry and an ELISA (Enzyme-Linked Immunosorbent Assay) method; and finally, carrying out freeze-drying treatment for long-term storage, and ensuring that the freeze-dried stem cells can effectively recover the immunocompetence. The prepared autologous stem cell preparation can be used for improving the immunity of a human body and has a relatively good application prospect.

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 present disclosure relates to isolated populations of cells comprising stable regulatory T cells and methods of producing the stable regulatory T cells. Some aspects provide an isolated population of cells comprising regulatory T cells (also referred to as Tregs) wherein: the regulatory T cells of the isolated population of cells comprise stable regulatory T cells (a) comprising an exogenous human T cell receptor (TCR) (also referred to as TCR-pMHC) that specifically binds to a target peptide complexed with the major histocompatibility complex (MHC), and (b) comprising a hypomethylated regulatory T cell specific demethylation region (TSDR) at the endogenous FOXP3 locus, at least 80% of the cells of the isolated population of cells being CD25 + / high CD4 + CD127- / lo regulatory T cells, and less than 10% of the cells of the isolated population of cells expressing FOXP3 protein from the engineered FOXP3 locus. The target peptide is typically a specific antigen peptide (agonist) in that it triggers intracellular signaling pathways that induce T cell mediated functions such as cytokine secretion and expression of genes required for inhibitory activity.

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.