118 results about "Cell kill" patented technology

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.

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 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.

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).

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 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 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.

Provided is a bispecific antibody targeting a CD3 molecule and a tumor associated antigen (TAA) HER2, comprising a first binding domain targeting the CD3 molecule and a second binding domain targeting HER2, wherein the first binding 5-domain only binds to an epsilon(ε) subunit in a delta(δ)-epsilon(ε) heterodimer of the CD3 molecule, and does not bind to an epsilon(ε) subunit in a gamma(γ)-epsilon(ε) heterodimer of the CD3 molecule. The antibody has the activity of activating immune cells and triggering relatively less cytokine release, recruits T cells, and achieves a cell killing effect.

The invention relates to the technical field of biological medicines, and particularly discloses a nanocapsule SMCPM and application thereof in medicines for treating or preventing osteosarcoma and pulmonary metastasis. The SMCPM is composed of a photosensitizer Ce6 carried by mesoporous silicon oxide-manganese oxide particles, an NRF2 inhibitor ML385 and an OS targeting peptide PT-7. Experiments prove that the SMCPM is high in penetrating power and strong in cell killing effect; by down-regulating NRF2 expression and reversing nuclear translocation, a biochemical inhibitory microenvironment can be effectively repaired, the tolerance of cells to active oxygen and epithelial-mesenchymal transition activated and induced by a NOTCH1 signal axis are remarkably reduced, the oxidative stress level of the cells is enhanced, and PIT-induced immunogenic cell death is promoted; the released Mn < 2 + > and double-stranded DNA can regulate and control an immunosuppressive microenvironment by activating an STING pathway in cells, thereby inhibiting the growth of osteosarcoma and preventing lung metastasis.

The invention relates to recombinant human lysozyme with broad-spectrum tumor cell killing activity and application of the recombinant human lysozyme. Specifically, the invention discloses a novel application of recombinant human lysozyme (ghLZ), and the recombinant human lysozyme is completely consistent with natural human lysozyme and does not have any variant. The ghLZ not only retains the broad bactericidal activity of gram-positive bacteria of natural human lysozyme, but also has unique broad-spectrum in-vitro tumor cell killing activity.

The present application relates to the technical field of nucleic acid drug preparation, and discloses a lipid nanoparticle based on asiatic acid and a preparation method and application thereof, the lipid nanoparticle is composed of ionizable cationic lipids, structural lipids, neutral lipids, PEG lipids and asiatic acid with a molar ratio of 10-85:20-60:1-30:0.1-10:0.1-50, and is used as a delivery carrier of nucleic acid drugs for delivering nucleic acid drugs. The present application innovatively uses natural product asiatic acid to partially replace the structural lipids (such as cholesterol) in the traditional LNP formula, significantly optimizes the micro morphology, and greatly enhances the transfection and expression efficiency of mRNA in vitro and in vivo. The mRNA vaccine based on the carrier can induce the body to produce high-titer specific antibodies and significantly enhance the cytotoxic T lymphocyte (CTL) killing activity. The LNP system performs outstandingly in the field of tumor immunoprevention and treatment, and shows superior conversion application potential and broad market prospects.

The application belongs to the technical field of biological medicine, and particularly relates to application of a KAT5 inhibitor in a medicine for enhancing the immunotherapy effect of natural killer cells, and a medicine for enhancing the immunotherapy effect of natural killer cells. The KAT5 inhibitor comprises at least one of Nu9056, TH1834 and MG149. The KAT5 inhibitor can inhibit the recruitment of a transcription factor SP1 to an ADAM10 promoter, reduce the transcriptional activity of ADAM10, reduce the expression of NKG2D ligands on the cell surface, and thus enhance the sensitivity of tumor cells to NK cell killing. The application first discloses a new mechanism in which KAT5 regulates an ADAM10-NKG2D signal axis through an epigenetic mechanism, and proves that the KAT5 inhibitor can significantly enhance the immunotherapy effect of NK cells in vitro and in vivo. The application provides a brand-new target and strategy for developing a new immunosensitizer and a combined cell therapy.

Provided are multispecific B7H3-targeting compounds and methods of using the same. The multispecific compounds include bispecific targeting proteins comprising a B7H3-targeting domain and an immune cell engaging domain, and trispecific targeting proteins comprising a B7H3-targeting domain, an immune cell engaging domain, and an immune cell activating domain. The methods of using include methods of inducing NK-mediated cell killing, methods of inducing NK in vivo expansion, and methods of treating cancer.

Disclosed herein is an anti-tumor pharmaceutical composition based on immune checkpoint blockade and use thereof. The anti-tumor pharmaceutical composition comprises: paroxetine hydrochloride, and a T-cell enhancer, wherein the T-cell enhancer is at least one of vitamin E and thymosin. Through a series of in vitro and in vivo experiments, cannabidiol and paroxetine hydrochloride were first found to be capable of effectively reducing the expression of PD-L1 on the tumor cell membrane, thereby blocking the PD-1 / PD-L1 signaling pathway and enhancing the ability of T cells to kill tumor cells. The T-cell enhancer added on this basis can further increase the quantity and activity of T cells, significantly increase the killing ability of T cells after immunosuppression is relieved, and greatly improve the anti-tumor effect of the drug. The components of the pharmaceutical composition used in the present invention, namely, cannabidiol, paroxetine hydrochloride, and vitamin E+thymosin, can exert a synergistic effect and improve the anti-tumor effect.

Provided are a C9-substituted camptothecin derivative and a conjugate thereof. Specifically disclosed is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The camptothecin derivative and the conjugate thereof have a good cell killing effect.

The application discloses a CAR-NK cell based on a dendritic molecule and a preparation method and application thereof. The CAR-NK cell is an assembly formed by the dendritic molecule, effectively loads nucleic acid expressing CAR through electrostatic interaction, forms a stable and uniform delivery system with nanometer size, is safely and effectively delivered to NK cells by virtue of the dendritic molecule, and prepares the CAR-NK cell with high-efficiency target gene expression, so as to solve the problems of low NK cell transduction efficiency and safety of a virus vector and improve the curative effect of the CAR-NK cell. The use of the dendritic molecule for transfection does not affect the phenotype of the NK cell and surface activation and inhibition receptors thereof. The CAR-NK cell prepared based on the dendritic molecule has a remarkable target cell killing efficiency in vitro and a remarkable anti-tumor (Raji-Luc transplanted tumor model) effect in vivo.

Methods and systems are provided for analyzing the ability of immune cells to kill target cells based on the effectiveness of mitochondria of the immune cells. The systems and methods further can be used for transplanting healthy mitochondria into immune cells to increase their effectiveness against target cells. The methods described herein can be used in treatment of cancer, mitochondrial diseases, and certain metabolic diseases.

The present application relates to signal conversion receptors, and specifically provides a signal conversion receptor comprising an extracellular region, a transmembrane region and an intracellular region, wherein the intracellular region comprises a CD25 intracellular domain, and optionally further comprises an intracellular domain of a costimulatory signaling molecule. An immune effector cell expressing the signal conversion receptor has a higher positive rate, activation level and target cell killing ability compared with a control cell.

The invention provides a camptothecin derivative and an antibody-drug conjugate thereof. The compound is high in activity, small in toxicity and good in affinity, the direct targeted killing effect on tumor cells is achieved through the compound and an antibody drug conjugate, and the antibody drug conjugate containing the antibody is remarkable in cell killing effect and has the very high tumor inhibition rate.

The invention relates to the technical field of immunotherapy, in particular to a method for preparing CAR-M and / or CAR-T with enhanced cell killing ability. The method comprises the steps that CAR-M and / or CAR-T are / is cultured on hydrogel, so that the CAR-M and / or CAR-T with the enhanced cell killing capacity are / is obtained, the hydrogel is gelatin-oxidized sodium alginate cross-linked hydrogel, and the oxidation degree is 50%; the material has the energy storage modulus of 1953 to 1120Pa, the loss modulus of 112.0 to 42.81 Pa, the loss coefficient of 0.06945 to 0.03730 and the stress relaxation coefficient of 2915 to 2019s. The CAR-M cell therapy is introduced into pulmonary fibrosis treatment for the first time, and hydrogel with optimal parameters is combined, so that the treatment efficiency of CAR-M / CAR-T cells is improved, the killing ability is improved by at least four times, and pulmonary tissue fibrosis is effectively relieved.

The invention relates to the technical field of nucleic acid medicine preparations, and discloses lipid nanoparticles based on asiatic acid and a preparation method and application thereof.The lipid nanoparticles are composed of ionizable cationic lipid, structural lipid, neutral lipid, PEG lipid and asiatic acid according to the molar ratio of (10-85): (20-60): (1-30): (0.1-10): (0.1-50) and serve as delivery carriers of nucleic acid medicine. For delivery of nucleic acid drugs. According to the invention, a natural product asiatic acid is creatively adopted to partially replace a structural lipid (such as cholesterol) in a traditional LNP formula, and the micromorphology of the LNP is obviously optimized, so that the in-vivo and in-vitro transfection and expression efficiency of mRNA is greatly enhanced. The mRNA vaccine constructed based on the vector can induce an organism to generate a high-titer specific antibody, and the killing activity of cytotoxic T lymphocytes (CTL) is remarkably enhanced. The LNP system has outstanding performance in the field of tumor immunoprophylaxis and treatment, and shows excellent transformation application potential and wide market prospect.

The invention relates to the technical field of biological medicine, in particular to an anti-B7H3 and CD3 bispecific antibody and application thereof. Aiming at the problem of lack of a bispecific antibody which simultaneously targets B7H3 and CD3 and can guide to kill tumor cells in the prior art, the invention provides the bispecific antibody for resisting B7H3 and CD3, and the bispecific antibody for resisting B7H3 and CD3 can be simultaneously combined with B7H3 and CD3 and can effectively mediate T cells expressing CD3 to kill cells expressing B7H3. According to the invention, the nano antibody targeting B7H3 and the anti-CD3 antibody OKT3 are constructed into the heterodimeric bispecific antibody, and the heterodimeric bispecific antibody still keeps good antigen binding activity; the prepared bispecific antibody has strong killing activity on B7H3 positive small cell lung cancer cells, effectively improves the treatment effect, and provides a key material for subsequent development of immunotherapy with efficient and lasting antitumor activity.