198 results about "Cell kill" patented technology

The present invention discloses a medical microsphere and its preparation method and application. The medical microsphere includes phenolic resin microspheres and radioactive metal elements loaded on the phenolic resin microspheres; the average particle size of the phenolic resin microspheres is 1 to 150 μm. The medical microsphere in the present invention can not only achieve local cell killing in the blood vessels of a specific part, but also effectively avoid the occurrence of fragmentation; further, the medical microsphere has a good loading rate and an extremely low exudation loss rate, which can meet the loading and safety requirements of radioactive elements; in addition, the preparation method of the medical microsphere is simple.

The invention relates to a strontium peroxide nano-material, which is characterized in that a strontium source, alkali and hydrogen peroxide are used as raw materials, a mixed solution of an organic solvent and water is used as a reaction solvent, the strontium peroxide nano-material is prepared under a template or template-free condition, and the strontium peroxide nano-material can quickly react with water to generate hydroxyl, hydrogen peroxide and oxygen, hydrogen peroxide can achieve a tumor cell killing effect, hydroxyl can neutralize an acidic tumor microenvironment and alkalify tumor cells, and oxygen can relieve a hypoxic tumor microenvironment. In addition, the strontium peroxide nano material can induce macrophages to be polarized to an anti-tumor M1 type by regulating and controlling glycometabolism of the macrophages, and remodeling an intra-tumor lactic acid metabolism crosstalk mode. The strontium peroxide nano-material or the modified material and the preparation thereof can be directly injected into a tumor or near the tumor under ultrasonic guidance to realize in-situ treatment, or can be delivered to a tumor supply blood vessel through a catheter to realize embolism treatment, so that the strontium peroxide nano-material or the modified material and the preparation thereof have a certain application prospect in the field of tumor treatment.

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 invention belongs to the technical field of biological medicines, and particularly relates to an antigen peptide library for inducing tumor specific immune response, the antigen peptide library comprises eight antigen peptides, and the amino acid sequences of the eight antigen peptides are respectively shown as SEQ ID NO.1-SEQ ID NO.8. The invention further discloses a preparation method of the antigen peptide library. The antigen peptide has high immunogenicity and can effectively stimulate and induce generation of specific cytotoxic T lymphocytes when being loaded on antigen presenting cells, in-vitro killing experiments show that CTL cells induced and activated by loading new antigen DC have a high tumor killing effect, and the cell killing activity of the CTL cells is 90% or above. When model mice are treated by adoptive T cell back-transfusion of CTL cells induced by the new antigen peptide library, the tumor volume can be effectively reduced, the survival rate of the tumor can be remarkably increased, and good treatment potential is achieved.

The present invention relates to a polypeptide-drug conjugate that binds to IL4Ra and a use thereof, and provides: a polypeptide comprising a ligand that specifically binds to IL4Ra and a temperature-responsive disordered domain; and a polypeptide-drug conjugate in which a cytotoxic drug is bound to the polypeptide. More specifically, the polypeptide, in which an IL4RA-binding ligand and a temperature-responsive disordered domain are repetitively linked, exhibits high selectivity in binding to IL4Ra, and the polypeptide-drug conjugate, in which a cytotoxic drug is bound to the polypeptide, demonstrates significantly enhanced cancer cell-killing efficacy and anti-tumor activity compared to unbound drugs or conventional anticancer agents, and has been confirmed to suppress drug resistance in cancer cells that are resistant to the anticancer agent temozolomide. Accordingly, the polypeptide-drug conjugate can be provided as an effective anticancer therapeutic agent for the treatment of tumors overexpressing IL4Ra and as a pharmaceutical composition for inhibiting drug resistance in cancer cells exhibiting resistance to anticancer drugs.

The invention provides a composition, and method of use thereof, comprising self-antigen displaying nanoparticles to target auto-reactive immune components for treating and / or preventing the autoimmune diseases associated therewith. The nanoparticles can also be loaded with cytotoxic drugs for targeted cell killing or with immune-tolerizing compounds to normalize the immune regulation.

The invention discloses a culture method for improving proliferation and differentiation capacity of NK (Natural Killer) cells based on angelica sinensis-astragalus membranaceus exosomes, which comprises the following steps: firstly extracting exosomes in angelica sinensis and astragalus membranaceus, then adding the exosomes into an NK cell culture system according to a specific concentration, and regulating and controlling an NK cell signal channel by virtue of active ingredients carried by the exosomes so as to improve the proliferation and differentiation capacity of the NK cells. Therefore, the proliferation rate and differentiation maturity of the NK cells are remarkably improved. Experimental results show that compared with a traditional culture method, the proliferation multiple of the NK cells cultured through the method is increased by 28.99%-33.69%, the proportion of differentiated mature cells is increased by 15.91%-28.30%, and the cell killing activity is not remarkably reduced. The method can be widely applied to the field of immune cell treatment, provides a high-quality NK cell source for clinic, effectively solves the problems of slow cell proliferation rate, low differentiation maturity, easy activity reduction after large-scale culture and the like in traditional NK cell in-vitro culture, and has important clinical application value and industrialization prospect.

Provided is an MUC1 binding molecule, comprising an MUC1 single domain antibody, which specifically binds to an MUC1 extracellular region. The present invention also relates to an anti-MUC1 single domain antibody-based chimeric antigen receptor and the use thereof. Specifically, provided is a chimeric antigen receptor having an antigen binding domain, wherein the antigen binding domain comprises an MUC1 binding molecule comprising the anti-MUC1 single domain antibody. An immune cell comprising the chimeric antigen receptor has a relatively high cell killing effect.

The present invention relates to a method for culturing natural killer cells derived from umbilical cord blood using transformed T cells. The method for culturing natural killer cells using transformed T cells according to the present invention can efficiently propagate and produce natural killer cells from a small amount of original cells. In addition, the method can also improve the cell killing ability of natural killer cells. Therefore, the method for culturing natural killer cells using transformed T cells according to the present invention can be usefully used to commercialize cell therapeutic agents. In addition, the natural killer cells produced by the culturing method of the present invention can be usefully used as cell therapeutic agents.

The invention discloses a generic tumor antigen antibody A11 and application thereof. The amino acid sequence of the CDR1 of the generic tumor antigen antibody A11 is as shown in SEQ ID NO. 1; the amino acid sequence of the CDR2 of the generic tumor antigen antibody A11 is as shown in SEQ ID NO. 2; and the amino acid sequence of the CDR3 of the generic tumor antigen antibody A11 is as shown in SEQ ID NO.3. The generic tumor antigen antibody A11 has strong affinity, a chimeric antigen receptor T cell taking the single-domain antibody as an antigen binding domain has strong killing ability to tumor cells, and the antibody can enhance the tumor cell killing ability of NK cells through ADCC effect.

MUC1 binding molecules are provided, including MUC1 single domain antibodies that specifically bind to the MUC1 extracellular region. The invention further relates to an anti-MUC1 single-domain antibody chimeric antigen receptor and application thereof, and particularly provides the chimeric antigen receptor, and an antigen binding domain of the chimeric antigen receptor comprises an MUC1 binding molecule containing the anti-MUC1 single-domain antibody. The immune cell containing the chimeric antigen receptor has a relatively high cell killing effect.

The invention relates to the field of drugs, in particular to a linker drug conjugate, an antibody drug conjugate, and a preparation method and application thereof. Specifically, the invention relates to a connexon drug conjugate, or a pharmaceutically acceptable salt, solvate or solvate of the salt, the connexon drug conjugate has a structure as shown in formula I, M is a chemical structure containing a maleimide (m) fragment or a cyclooctyne fragment, x is a connecting fragment composed of 1-5 amino acids or derivatives thereof, and D is cytotoxin. The linker drug conjugate disclosed by the invention can release Payload through an enzymolysis reaction under the condition that a hydrophobic structure PAB is removed, so that the hydrophobicity of Linker-Rug can be reduced, the content of a polymer generated during preparation of ADC can be reduced, and corresponding cell killing activity (M-X-D formula I) can also be shown.

The disclosure belongs to the technical field of medicine. Provided are a CD97 and GSDME interaction inhibitor having anti-tumor activity and an application thereof. A compound screened in the disclosure enhances the susceptibility of NK cells to kill tumor cells by inhibiting the interaction between GSDME and CD97 in tumor cells, so as to induce an immune anti-tumor effect. Moreover, the compound enhances the susceptibility of tumor cells to pyroptosis by blocking the protective effect of CD97 on cleavage of GSDME proteins. Therefore, the compound can be used for treating GSDME and CD97 double-positive malignant tumors, and combined chemotherapy, immunotherapy, etc., to enhance the susceptibility of malignant tumors to chemotherapy and immunotherapy, prolonging the overall survival period of patients with malignant tumors. Specifically provided is a compound having a structure set forth in formula (I), a pharmaceutically acceptable salt, a solvent compound or a deuterated compound thereof.

The invention relates to a selective cell killing device based on surface and interface pH regulation and application thereof. The method comprises the following steps: depositing a noble metal material capable of regulating and controlling extracellular proton concentration on one side of a substrate to form a regulation and control layer, and connecting the regulation and control layer to an external preset dynamic voltage control unit through a wire; the regulation and control layer is attached to the surface of the tissue; a dynamic voltage is periodically applied to the regulation and control layer through an external preset dynamic voltage control unit, so that the pH value of the interface microenvironment of the regulation and control layer and tissue cells is alternately changed between 5 and 8, and accurate selective killing of the cells is realized. A preset dynamic voltage control scheme based on a cancer cell glycolysis oscillation period is adopted, so that the pH value of a local surface interface can be regulated and controlled according to a set period, the excretion of lactic acid and protons of cancer cells is continuously and effectively interfered, and the cancer cells are prevented from generating adaptive reaction.

The present invention provides a method of determining the relative potency of a viral vector encoding a chimeric antigen receptor (CAR), the method comprising: a. providing a sample viral vector to be analysed (sample vector) and a reference viral vector of known potency (reference vector); b. transducing separate Effector cell populations with the sample vector and reference vector at various multiplicities of infection (MOIs) to form a group of transduced sample Effector cell populations and a group of transduced reference Effector cell populations; C. conducting cell impedance-based real-time cell killing assays of Target cells using the transduced sample Effector cell populations and the transduced reference cell populations; d. generating a cytotoxicity versus MOI curve for the transduced sample Effector cell populations and for the transduced reference cell populations; e. comparing parallelism of the curves generated in step (d), wherein parallel curves indicate comparable data sets; f. determining the half maximal effective concentration (EC50) of the sample Effector cell population and the reference cell population; and g. comparing the EC50 of the transduced sample Effector cell population and the transduced reference cell population to determine the relative potency of the sample viral vector.

The invention relates to the field of biological medicine, in particular to application of NPEPL1-targeted small molecule compounds in preparation of tumor targeted therapy drugs, and four small molecule compounds, namely C301-9181, E859-1332, L281-0443 and C679-2629, which have a hepatocellular carcinoma cell killing effect and high NPEPL1 affinity are obtained for the first time. The small molecule compound realizes tumor targeted therapy by targeting NPEPL1 protein in tumor cells, and can be used for developing tumor targeted therapy drugs. According to the present invention, the potential treatment effect of the targeted intervention NPEPL1 on hepatocellular carcinoma and other malignant solid tumors with high NPEPL1 expression is provided, the optimal small molecule compound C301-9181 is obtained through layer-by-layer screening, the small molecule compound can be used for preparing the NPEPL1-targeting anti-tumor targeting drugs, the drug research and development blank in the NPEPL1 targeting treatment field is filled, and the broad application prospect is provided.

The present application relates to the fields of bioengineering and technology, and specifically to a method for resuscitating and culturing ROBO1CAR NK cells. The method comprises: resuscitating and culturing the cells using a resuscitation medium, wherein the resuscitation medium is a serum-free HIPP-T009 lymphocyte culture medium containing IL-2 and nicotinamide; performing a primary amplification culture on the resuscitated cells using a first amplification culture medium to obtain primary amplified cells; and performing a secondary amplification culture on the primary amplified cells using a second amplification culture medium to harvest the cells. The method can rapidly resuscitate frozen cells, effectively maintain cell growth and cell killing activity, and expand the culture scale, greatly reducing the culture cycle and production costs.

The invention relates to the technical field of immunology and biology, in particular to a light chain variable region and a heavy chain variable region of a rabbit anti-canine CD3E monoclonal antibody and application of the light chain variable region and the heavy chain variable region. The rabbit anticanine CD3E monoclonal antibody is successfully developed, and the antibody can be applied to experiments such as ELISA (enzyme-linked immunosorbent assay), flow cytometry, immunohistochemistry, stimulation of canine T cell activation and the like. Meanwhile, after being transfected to the surface of a tumor cell, the T cell can be promoted to kill the tumor. The development of the antibody provides a basic tool for detection and subsequent tumor immunotherapy. Meanwhile, the problems of low affinity, poor antigen specificity and the like of a traditional antibody are solved, the performance of the antibody is improved, and the application scene of the antibody is expanded.

The invention belongs to the field of biomedicine, and particularly relates to a detection method, an evaluation method and application of umbilical cord blood-derived natural killer cells. The detection method disclosed by the invention is used for carrying out related detection and data analysis on the natural killer cells from umbilical cord blood, is high in pertinence and can be used as a detection method for delivering the NK cells from a warehouse. According to the evaluation method, the relationship between the NK function related protein and the cell killing ability is determined, the killing ability of the NK cells is judged by detecting functional protein indexes CD3, NKG2A, CD56, CD16, NKP46 and CD107A of the natural killer cells and calculating NK scores of samples based on detection results, the sensitivity and specificity are high, and the method can be used for evaluating the killing ability of the NK cells.

The invention discloses a TOPK antigen HLA-A2 restrictive CTL (cytotoxic T lymphocyte) epitope peptide, and belongs to the technical field of biological medicines. The amino acid sequence of the epitope peptide is as shown in any one of SEQ ID NO.1-4. The epitope peptide obtained by identifying and screening the TOPK antigen through intracellular factor staining, cell killing experiments and the like can effectively induce specific CTLs and has a killing effect on tumor cells, so that the epitope peptide can be used as an important target spot for tumor immunotherapy, is used for designing targeted polypeptide vaccines and has a wide application prospect.

A bispecific antibody binding to BCMA and CD3, and a preparation method therefor and the use thereof. A bispecific antibody, which can bind to BCMA and CD3 simultaneously, has specific targeting effects and can efficiently stimulate directed immune responses. The bispecific antibody retains the biological functions of an anti-CD3 antibody and an anti-BCMA antibody, enables the bispecific antibody molecule to achieve excellent biological functions of simultaneously binding to BCMA and CD3 in a targeted manner, forms a bridge between tumor cells and immune effector cells, effectively activates the immune effector cells and the directed immune responses, significantly enhances the effects of immune cells in killing tumor cells, has a high targeted cell killing efficiency, reduces the ADCC effect to the largest extent, has high safety, and has good application prospects in tumor immunotherapy.

Provided are a compound capable of killing bacteria and viruses and a manufacturing method therefor. The compound comprises an effective amount of a mixture formed by an oleophylic phase ingredient and at least a food-grade nano-calcium-containing ingredient. By heating the mixture at 100 °C and then letting to stand at room temperature for cooling, the compound is obtained. When the compound is applied at pathogen-hiding sites on the skin, calcium ions in the food-grade nano-calcium-containing ingredient will trigger physiological reactions such as phagocytosis of macrophages, intercellular signal transmission, hormone secretion, and the like, to antagonize foreign pathogens; in addition, calcium ions will also be adsorbed on cell membranes of bacteria or viruses to denature cell proteins, which disables cell breath, metabolism, and proliferation and ultimately causes cell death, thus completing cell killing and achieving the effects of killing bacteria and viruses.

The application discloses a nano-antibody (also known as single-domain antibody) conjugated photosensitizer targeting HER2, a preparation method of the photosensitizer and application of the photosensitizer in tumor photodynamic therapy. The photosensitizer is shown in a general formula (I). In the photosensitizer, the nano-antibody (N HER2 ) serving as a targeting ligand is connected with a photosensitive moiety (PS) through a catalytic reaction mediated by a transglutaminase (MTGase). Research finds that the anti-HER2 nano-antibody conjugated photosensitizer molecule has good cell killing selectivity and tumor enrichment capacity, and can remove a subcutaneous tumor of a mouse with high HER2 expression in one administration. HER2 -PEG 1K -PS (I).

Artificial expression constructs including a dnSHP1, caBCL2, dnNRDP1, PCK1, cFLIP.v3, caAKT, survivin, or dnFADD transgene under the control of an inducible promoter are described. The artificial expression constructs can be used to enhance the function of a recombinant receptor-immune cell (e.g., CAR T-cell). The dnSHP1, caBCL2, dnNRDP1, PCK1, cFLIP.v3, caAKT, survivin, or dnFADD transgene disclosed herein enhances the potency of the recombinant receptor-immune cell (e.g., CAR T-cell), resulting in potentiated cell killing ability, proliferation, cytokine output, and / or maintenance of artificial expression construct positivity.

Highly potent antibody-drug conjugates (ADCs) targeting fibroblast growth factor receptor (FGFR4) are described. The ADCs contain an FGFR4-specific monoclonal antibody or antigen-binding fragment thereof conjugated to an anti-cancer drug, such as monomethyl auristatin E (MMAE) or exatecan. The ADCs exhibit selective cell killing for FGFR4-expressing cells in vitro, and significantly decrease tumor volume and increase survival in animal models of FGFR4-expressing tumors.

The invention provides a polymer lipid hybrid nanoparticle with T cell activation ability, which is characterized in that the polymer lipid hybrid nanoparticle comprises a cationic polymer, an auxiliary lipid, cholesterol and a polyethylene glycol derived lipid, and the cationic polymer comprises a copolymer prepared from polyethyleneimine and p-toluenesulfonyl arginine. The polymer lipid hybrid nanoparticles provided by the invention have dual capabilities of T cell activation and transfection, can realize one-step activation and transfection of primary T cells, greatly shortens the preparation period, and reduces the preparation complexity. Besides, CAR-T cells generated by delivering CAR mRNA through the polymer lipid hybrid nanoparticles RT LNP have excellent cell killing ability in vitro, and can specifically secrete killer cytokines, so that specific and efficient killing of target cells is realized, and the CAR-T cells have good application prospects. It is verified that the polymer lipid hybrid nanoparticles developed in the invention are a promising platform for rapid production of mRNA CAR T cell products.

The present invention relates to the identification of key residues within mouse IgG3 antibodies (mAbs) that are responsible for intermolecular cooperativity and their transfer into IgG1 antibodies in order to enhance their functional affinity and direct a cell killing.

The invention discloses a clinical diagnosis reagent for human head and neck squamous cell carcinoma, which is a reagent for detecting the expression level of human NCAPH gene, the expression level of the human NCAPH gene is in negative correlation with clinical prognosis of the human head and neck squamous cell carcinoma, and experimental results show that the expression of the human NCAPH gene in a human head and neck squamous cell carcinoma cell line is higher than that of normal nasopharyngeal epithelial cells. By knocking down the expression of the human NCAPH gene, the proliferation of head and neck squamous carcinoma cells and the clone sphere forming ability can be remarkably inhibited; the invention further provides a medicine for inhibiting human NCAPH gene expression or an NPIDP small peptide medicine for inhibiting human PD-L1 gene expression, the NPIDP small peptide medicine acts on human head and neck squamous carcinoma cells, combination of NCAPH and HIP1R can be remarkably and competitively blocked, degradation of PD-L1 protein is promoted, and therefore the T cell killing effect is enhanced, and the NPIDP small peptide medicine can be used for treating human head and neck squamous carcinoma cells. The invention provides a novel diagnosis and treatment medicine for treatment of human head and neck squamous cell carcinoma.

The invention discloses a drug-loaded nanoparticle as well as a preparation method and application thereof. The drug-loaded nanoparticles comprise active components and a carrier, wherein the active components comprise a hydrophobic small-molecule inhibitor and PAEMA; the carrier comprises an amphiphilic polymer bonded with a photosensitizer; the amphiphilic polymer bonded with the photosensitizer is coated with a hydrophobic small-molecule inhibitor and PAEMA (Polyacrylamide); wherein the amphiphilic polymer bonded with the photosensitizer comprises the photosensitizer, a hydrophilic chain segment and a hydrophobic chain segment. Precise drug delivery is achieved through characteristic transformation of the nano-carrier driven by tumor acidity, M2 type macrophages can be removed, dendritic cells can be induced to be mature, tumor cells can be killed, and therefore the synergistic anti-tumor effect of photodynamic therapy and immunotherapy is enhanced. Therefore, various drugs can be accurately delivered to target cells with different spatial distributions, so that the cell killing level and the antigen presenting cell mediated immunocompetence are enhanced at the same time.