35 results about "Secretory cell" patented technology

The invention belongs to the technical field of biological medicines, and discloses a traditional Chinese medicine composition for treating microsatellite stability (MSS) type tumors by a sensitization immune checkpoint inhibitor. The traditional Chinese medicine composition provided by the invention comprises radix scutellariae, rhizoma zingiberis, Chinese herbaceous peony, liquorice root and Chinese date, can increase CD8 + T cell infiltration, promote the CD8 + T cell to secrete cytokines and improve the immunosuppression of MSS type tumors, and further breaks through the conventional range of anti-tumor treatment of immune examination inhibitors; meanwhile, the traditional Chinese medicine composition can also improve adverse reaction of gastrointestinal tracts caused by tumor treatment by an immune examination inhibitor, and the life quality of patients is improved.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 4 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

The invention relates to an up-regulation Nuak1 immune cell and application thereof, and particularly provides an over-expression Nuak1 immune cell and application thereof in preparation of drugs for treating diseases. Specifically, up-regulation of the Nuak1 in immune cells can significantly improve the toxicity, proliferative activity and cytokine or GZMB secretion ability of the immune cells, and further has the effect of enhancing tumor treatment.

The invention relates to a functionalized cartilage tissue repair material as well as a preparation method and application thereof, and belongs to the technical field of tissue engineering. The invention aims to solve the problems that the existing decalcified bone matrix is insufficient in cartilage induction in cartilage repair, and is easy to cause blood vessel ingrowth and fibrosis repair. The preparation method comprises the following steps: inoculating cartilage cells on a three-dimensional porous frame structure carrier, carrying out in-vitro dynamic pre-culture to enable the cartilage cells to secrete an extracellular matrix, and carrying out decellularization treatment to obtain the functionalized cartilage tissue repair material retaining the cartilage specific matrix. The material has a suitable pore structure and abundant II-type collagen deposition, can effectively promote chondrocyte differentiation and hyaline cartilage regeneration, inhibits blood vessel ingrowth, maintains a cartilage vascular-free microenvironment, significantly improves the structure and function reconstruction effect of cartilage defect repair, and has good biocompatibility and clinical transformation potential.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 4 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. A preferred co-stimulatory domain is CD28 or 41-BB. The humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

The present application relates to the technical field of biological medicine, in particular to an anti-CEACAM5 antibody and application thereof, the anti-CEACAM5 antibody has the following technical features: the heavy chain variable region includes CDR-H1 with the amino acid sequence shown in SEQ ID No.1, CDR-H2 with the amino acid sequence shown in SEQ ID No.2 and CDR-H3 with the amino acid sequence shown in SEQ ID No.3.The anti-CEACAM5 antibody has high affinity, is used as an antigen binding domain to construct a chimeric antigen receptor, and utilizes the chimeric antigen receptor to prepare a CAR-T cell, the CAR-T cell has killing activity on tumor cells positive for CEACAM5, and after co-culturing with CEACAM5-positive cells, the CAR-T cell can efficiently secrete the cytokine IFN-gamma, the nanobody can be effectively applied to immunotherapy, and has important significance for developing tumor treatment drugs.

The present application belongs to the field of biomedical technology, and particularly relates to a cell-derived extracellular matrix and a preparation method and application of a cell culture plate coated with the cell-derived extracellular matrix. The present application cultures human astrocytes in a cell culture plate, and makes the human astrocytes secrete extracellular matrix. After the human astrocytes are added into a cell lysate for cell removal treatment, nucleic acid fragmentation treatment is performed to obtain the cell-derived extracellular matrix. The present application has relatively simple operation, short time period, and can realize batch production of extracellular matrix without external virus carrying and stable components. The obtained cell-derived extracellular matrix is resistant to storage, has good stability, is highly similar to a natural brain environment when coated on a cell culture plate, has good biocompatibility with cells, can be applied to tissue repair and regeneration as an ideal biomedical material, can regulate the progress and efficiency of human dermal fibroblast HDF transdifferentiation into neurons, and can obtain in-vitro survival neurons.

The application belongs to the field of biological medicine, and particularly relates to application of DJ-1 in treatment and diagnosis of bronchial asthma. DJ-1 is used as a target in preparation or screening of drugs for bronchial asthma or allergic inflammation; a drug for treating hyperplasia of goblet cells and mucus metaplasia in bronchial asthma, and an animal model for studying inhibition of differentiation of goblet cells and mucus metaplasia. The application identifies, for the first time, an important role of a signal pathway DJ-1 / Ltc4s, which has not been found in eosinophils and lung epithelial cells before, in differentiation of secretory cells into goblet cells, and finds, for the first time, an inhibitory effect of inhibition of the DJ-1 / Ltc4s signal pathway on differentiation of goblet cells in lung epithelial cells through a large number of studies.

The invention belongs to the technical field of vaccines, and particularly relates to a manganese-based platelet carrier vaccine based on a biomimetic mineralization technology and application of the manganese-based platelet carrier vaccine in immunotherapy. A manganese-based shell is deposited on the surface of a platelet, immunocompetence molecules such as CD40L and PF4 are expressed on the surface of the platelet, dendritic cells (DC) can be activated by directly contacting or secreting cell factors, and antigen presentation is promoted; in addition, deposited manganese ions can activate a cGAS-STING pathway, and meanwhile, CD40 / CD80 / CD86 / MHC-II costimulatory molecular expression on the surface of the DC is up-regulated. The vaccine adjuvant provided by the invention can be used for loading an antigen to form a three-in-one vaccine complex of the antigen (loaded on a platelet membrane), the platelet and a manganese shell, so that not only is the natural targeting capability of the platelet retained, but also DC cross presentation is enhanced through continuous release of manganese ions, finally CD8 + T cells are synergistically activated to react with an antibody, and the immune response of the antigen is enhanced. The antiviral immune response of the body is enhanced.

Provided is a technique capable of evaluating a property of a secretion product with high accuracy.　Specifically provided are a secretion product evaluation method and others, the secretion product evaluation method comprising: a positional information identification step for identifying positional information of at least one secretory cell and at least one antigen-holding particle on the basis of optical information relating to a carrier that holds the secretory cell and the antigen-holding particle; a secretion product information acquisition step for acquiring information relating to a secretion product that binds to a binding target molecule held by the secretory cell and the antigen-holding particle; and a secretion product evaluation step for evaluating a property of the secretion product on the basis of the positional information and the information relating to the secretion product.

The present invention relates to a method for producing respiratory organoids by proliferating and differentiating respiratory epithelial cells. [Solution] Unlike conventional respiratory organoids in which epithelial cells present at the apical end of the respiratory tract develop inside the organoid, the respiratory organoid of the present invention has a morphology in which the ciliated structure, which is made up of epithelial cells, is located in the outer layer of the organoid, secretory cells are located inside, and stem cell-like basal cells present at the base of the respiratory tissue are also located inside the organoid. This morphology is similar to that of actual respiratory tissue and has been observed to exhibit normal functions of epithelial cells, such as the motility of ciliated cells. Therefore, by manufacturing organoids using the manufacturing method of the present invention, it is possible to manufacture respiratory organoids that can accurately mimic actual tissue.

The application discloses an anti-DLL3 nanobody, related products and purposes. The nanobody comprises a heavy chain variable region of CDR1, CDR2 and CDR3, the amino acid sequence of the CDR1 is shown in one of SEQ ID No. 1-SEQ ID No. 6; the amino acid sequence of the CDR2 is shown in one of SEQ ID No. 7-SEQ ID No. 12; and the amino acid sequence of the CDR3 is shown in one of SEQ ID No. 13-SEQ ID No. 18. The anti-DLL3 nanobody of the application only comprises a heavy chain variable region, can specifically recognize a DLL3 antigen on a cell surface, the constructed CAR-T cell has killing activity on tumor cells positive to DLL3, can efficiently secrete a cytokine IFN-gamma, can be effectively applied to immunotherapy, and has important significance for developing tumor treatment drugs.

This invention provides a method for modeling a fracture healing model under the influence of macrophages. The steps are as follows: Step 1: Establish a mathematical model of fracture healing based on the ordinary differential equation of fracture healing; Step 2: Establish a fracture healing model under the influence of macrophages based on the regulatory effects of macrophages and their secreted cytokines on bone tissue cells. This invention provides a mathematical description of the complex process of fracture healing based on the interaction between the immune system and bone tissue cells in the human body, and has theoretical guiding significance for studying the mechanism of fracture healing and treating fractures.

The utility model belongs to the field of biotechnology, and particularly relates to a device for preparing a multi-layer cell sheet, which comprises a clamp and a culture box for placing the clamp, the clamp comprises a clamp cover plate and a clamp base. The clamp cover plate is connected to the upper portion of the clamp base. The clamp cover plate is provided with a plurality of cover plate hollowed-out openings, the clamp base is provided with a plurality of base hollowed-out openings, and the cover plate hollowed-out openings and the base hollowed-out openings in the same position are the same in shape. Limiting structures are arranged on the four edges of the clamp base, and the cell sheets are pressed between the limiting structures by the clamp cover plate and then fixed between the clamp cover plate and the clamp base. Compared with the prior art, the positions of the cell sheets in the clamp can be fixed through the cell sheet fixing pieces, the cell sheets are kept in contact in the culture process, then intercellular connection is generated or extracellular matrixes are secreted, and multiple layers of cell sheets are prepared at a time under the condition of not depending on exogenous extracellular matrixes.

Relates to an application of an anti-TSLP antibody or an antigen-binding fragment thereof and a nucleic acid molecule encoding the antibody in preparation of drugs for preventing and / or treating asthma, allergic inflammation, anaphylaxis or autoimmune diseases, the antibody or the antigen-binding fragment thereof has high affinity to TSLP, can effectively bind to TSLP and block the proliferation effect of TSLP on Ba / F3-hTSLPR-hIL7R alpha cells, and can be used for preparing drugs for preventing and / or treating asthma, allergic inflammation, anaphylaxis or autoimmune diseases. And the TSLP is capable of blocking the activation of PBMC (peripheral blood mononuclear cells) and secreting cytokines.

This invention discloses a type B influenza virus T4 peptide that can induce cellular immune responses and its applications, belonging to the fields of immunotherapy and immunoassay technology. The immunogenicity of this long peptide (SEQ ID NO.1, named T4) was verified in 21 volunteers using ELISpot assay. Results showed that T4 was positive in 5 individuals, with a positive rate of 23.81%. ELISpot assay of human PBMCs (IFN-γ secretory cells) showed that T4 induced an immune response of up to 3060 SFCs / 10 in the population. 6 PBMC. Therefore, this peptide has good immunogenicity and universality in the population, and can be used as a specific detection peptide for monitoring cellular immune levels. At the same time, this peptide can effectively activate the T cell immune response in the population, and has the potential to be used as a candidate vaccine epitope peptide for the design of novel vaccines.

CD40 activating proteins comprising recombinant proteins with CD40 agonist antibodies or their antigen-binding fragments fused or linked to CD40 ligand are provided. The CD40 activating proteins may further comprise at least one antigen. Uses for the CD40 activating proteins include inducing immune responses directed to delivered antigens such as viral or cancer antigens. Properties of the CD40 activating protein may include the ability to induce proliferation of B cells or secretion of cytokines, such as IL-6, IL-12 and / or IL-15.

An in vitro method of preparing insulin-producing cell clusters for transplantation into a subject, comprising (a) seeding pancreatic progenitor cells onto a three-dimensional, porous scaffold at a seeding density greater than about 12.5 million cells per cm3 of scaffold and less than about 150 million cells per cm3 of scaffold, wherein the scaffold comprises a plurality of pores having an average pore diameter greater than about 225 μm and less than about 550 pm, and (b) culturing the cells on the scaffold for more than about 3 days in culture medium to obtain insulin-producing cell clusters within the pores of the scaffold for transplantation into a subject. In exemplary aspects, the pancreatic progenitor cells are cells derived from pluripotent stem cells.

Neuroendocrine tumors (NETs) are a class of highly heterogeneous tumors derived from neuroendocrine cells. Synaptic vesicle 2 (SV2) protein is a novel marker of NETs, and there are three subtypes of SV2A, SV2B and SV2C, wherein the structure of SV2C is more stable than the other two, and the largest cavity ring L4 thereof is the most important binding area with toxins. The present application obtains a nanobody of the extracellular soluble part L4 of SV2 by screening through phage display technology, and the nanobody labeled with a fluorescein, a small molecule of a chemical toxin or a nuclide is used to prepare a probe molecule, and the result can be specifically combined with neuroendocrine tumor cells. The present application provides a nanobody of the extracellular soluble part L4 of SV2, and the nanobody can be applied in the preparation of diagnostic and therapeutic preparations for neuroendocrine tumors.

This invention discloses a method for activating stem cell function based on low-intensity pulsed ultrasound, belonging to the field of stem cell technology. This invention uses low-intensity pulsed ultrasound for activation, achieving the activation effect on stem cells solely through an ultrasound therapy device. The ultrasound generator is reusable, resulting in extremely low long-term costs and significantly reducing treatment costs. Given the scarcity and high price of stem cells, this method significantly increases stem cell proliferation efficiency, leading to a substantial increase in yield. Experimental data demonstrates that using low-intensity pulsed ultrasound to stimulate various types of stem cells can enhance their proliferation, migration, and paracrine cytokine effects. It also significantly strengthens the positive influence of stem cells on other tissue cells through paracrine effects, thus achieving a good activation effect.

PROBLEM TO BE SOLVED: The purpose of the present invention is to provide a compound capable of safely and efficiently introducing into cells an antibody drug capable of inhibiting proliferation of cancer cells. SOLUTION: According to the present invention, the proliferation of cancer cells is suppressed by introducing an antibody that binds specifically to IL-6 or a receptor thereof into cells using the PIECE method and specifically suppressing the autocrine intracellular IL-6 signaling pathway. This configuration makes it possible to target a pathogenic signaling pathway localized in a cell, and to provide a novel and practical technique for intracellular delivery of antibody drugs and cancer treatment methods that overcomes the application limits of conventional antibody drugs.

The invention discloses a guided dental pulp stem cell extracellular matrix nerve scaffold and a preparation method thereof, and belongs to the technical field of biological materials. The method comprises the following steps: culturing dental pulp stem cells, stimulating the dental pulp stem cells to secrete an extracellular matrix, and carrying out decellularization treatment to obtain DPSC-dECM; the preparation method comprises the following steps: preparing the DPSC-ECM into a suspension, mixing the suspension with a PLCL solution, spinning by adopting an electrostatic spinning technology to form an oriented DPSC-ECM membrane, rolling to form a catheter inner layer, spinning a PLCL fiber layer on an outer layer, and drying to obtain the double-layer tubular nerve stent. The inner layer of the stent is composed of DPSC-ECM / PLCL composite oriented nanofibers, and can provide active biological signals and oriented physical guidance at the same time, effectively maintain Schwann cell repair phenotypes, significantly enhance cell adhesion, proliferation, oriented migration, autophagy and secretion functions, and promote angiogenesis at the same time, thereby achieving good axon regeneration; the outer layer PLCL fiber provides mechanical support; the problems that a traditional nerve repair material is difficult to maintain the Schwann cell repair function and is insufficient in guidance are solved, and a new strategy is provided for peripheral nerve defect repair.

The application 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 having HLA-G binding activity; and a second antigen binding region having CD3 binding activity; wherein the first antigen binding region comprises an anti-HLA-G antibody, and the anti-HLA-G antibody comprises a heavy chain complementarity determining region (HCDR) comprising an amino acid sequence selected from at least one of SEQ ID NO: 1-3 or a conservatively modified form thereof. The bispecific antibody can bind to CD3 and HLA-G, thereby promoting T cell activation, proliferation and secretion of cytokines, effectively promoting PBMC killing of tumor cells, and having good anticancer activity. Moreover, the bispecific antibody has low binding activity to T cells and high binding activity to tumor cells, and has good clinical application value and drug development value.

The present invention relates to a method comprising the steps of a) contacting ex vivo a cell from a mammalian cell line capable of secreting cytokines in a liquid medium with a set of antibodies from a blood sample from a mammalian subject which is known to be healthy or to suffer from a first disease; b) detecting the level of at least one cytokine present in the liquid medium following step a); c) contacting ex vivo a cell from the mammalian cell line capable of secreting cytokines with a set of antibodies from a blood sample from a mammalian reference subject which is known to be healthy or to suffer from a second disease in a liquid medium; d) detecting the level of the at least one cytokine present in the liquid medium following step c); e) determining a cytokine signature by determining the difference between the level of the at least one cytokine determined in step b) and the level of the at least one cytokine determined in step d), wherein the method is a method for aiding in detecting or diagnosing a disease, a method for aiding in distinguishing between a first disease and a second disease, or a method for aiding in diagnosing whether a mammalian subject is likely to suffer from a disease.

The invention discloses a method for enhancing the function of CAR-T (Chimeric Antigen Receptor-T) cells. Specifically, the invention discloses application of Id2 protein in enhancing CAR-T cell activation, proliferation, tumor growth killing and inhibiting ability, cytokine secretion ability, durability and / or anti-tumor effect. The invention also discloses a method for enhancing the function of the CAR-T cell. The method comprises the step of improving the content and / or activity of Id2 protein in the CAR-T cell. According to the invention, Id2 is fused on a CAR gene to construct an Id2 overexpressed CAR-T cell, and experiments prove that Id2 protein can enhance the durability, activation and proliferation ability, killing ability, cytokine secretion ability and the like of the CAR-T cell, and Id2 overexpression can significantly enhance the killing ability of the CAR-T cell to tumor cells no matter in human or mouse CAR-T cells, so that the CAR-T cell can be used for treating tumor cells. The anti-tumor effect is improved, so that the CAR-T cell has a stronger tumor treatment effect.

The present disclosure provides a method for producing extracellular vesicles derived from lung progenitor cells or differentiated cells thereof, wherein said method includes a step (1) in which, by culturing lung progenitor cells, extracellular vesicles are secreted from the lung progenitor cells or differentiated cells thereof in a medium.

Relates to an application of an anti-TSLP antibody or an antigen-binding fragment thereof and a nucleic acid molecule encoding the antibody in preparation of drugs for preventing and / or treating asthma, allergic inflammation, anaphylaxis or autoimmune diseases, the antibody or the antigen-binding fragment thereof has high affinity to TSLP, can effectively bind to TSLP and block the proliferation effect of TSLP on Ba / F3-hTSLPR-hIL7R alpha cells, and can be used for preparing drugs for preventing and / or treating asthma, allergic inflammation, anaphylaxis or autoimmune diseases. And the TSLP is capable of blocking the activation of PBMC (peripheral blood mononuclear cells) and secreting cytokines.

The application discloses a CD40 antibody or antigen binding fragment and application thereof. The CD40 antibody or antigen binding fragment has strong binding capacity with hCD40, can activate a CD40 / CD40L signal transduction pathway and downstream regulation signals thereof, can induce human B cell activation and significantly up-regulate CD95 protein expression, can promote B cell proliferation, can induce human PBMC-derived iDC cell activation and secrete a cytokine IL-12. The CD40 antibody or antigen binding fragment does not have ADCC effect, ADCP effect and CDC effect, can significantly reduce tumor volume / weight without affecting mouse body weight, prolong the survival time of mice, has good drug metabolism kinetics, and can be used for detecting hCD40 expression level and treating tumors.

The present application relates to the technical field of biological medicine, in particular to an anti-CD66e antibody and application thereof, the anti-CD66e antibody has the following technical features: the heavy chain variable region includes CDR-H1 with the amino acid sequence as shown in SEQ ID No. 1 or 2, CDR-H2 as shown in SEQ ID No. 3 or 4 and CDR-H3 as shown in SEQ ID No. 5 or 6. The anti-CD66e antibody has higher affinity, is used as an antigen binding domain to construct a chimeric antigen receptor, and utilizes the chimeric antigen receptor to prepare a CAR-T cell, the CAR-T cell has killing activity to tumor cells positive to CD66e, and after being co-cultured with CD66e positive cells, can efficiently secrete a cytokine IFN-gamma, the nanobody can be effectively applied to immunotherapy, and has important significance for developing tumor treatment drugs.

This invention discloses a 3D cell sphere for treating skin defects, its preparation method, and its applications, belonging to the field of biomedical materials. The 3D cell sphere is formed by the self-assembly of keratinocytes (KCs) and cells capable of secreting extracellular matrix, possessing a biomimetic hierarchical structure similar to natural skin, filled with extracellular matrix, and the KCs can form functional epidermal-associated structures. The preparation method involves obtaining EKCs through directed induction differentiation of pluripotent stem cells, which are then spontaneously assembled with cells capable of secreting extracellular matrix to form 3D cell spheres. The 3D cell sphere exhibits excellent biocompatibility, a simple preparation process, and can be mass-produced, with convenient operation. It is suitable for repairing various acute and chronic skin defects such as large-area thermal burns, diabetic foot ulcers, and pressure ulcers, effectively accelerating wound healing and improving the quality of epidermal regeneration. It addresses the pain points of traditional treatments, such as scarcity of skin cells, complex procedures, and poor efficacy, providing a safe and efficient novel cell therapy for skin defect repair.