1023 results about "Cellular Cytotoxicity" patented technology

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK / NK-92 cells.

The invention belongs to the technical field of cytotoxicity intervention, and particularly relates to application of an iNOS inhibitor in preparation of a medicine for relieving cellular injury caused by toxin combined exposure. KK-1 cells serve as a research model, it is shown for the first time that MC-LR and NaNOS combined contamination can remarkably up-regulate the expression level of iNOS protein, and it is found through tests that Nos2 gene silencing can remarkably relieve tight junction damage and cell apoptosis caused by toxin combined exposure in the KK-1 cells; it is revealed for the first time that iNOS is a core target of toxin combined exposure induced cell tight junction damage and apoptosis, and the blank of toxic mechanism research in toxin combined exposure is filled. The application provides a new direction for a detoxification strategy of environmental toxin combined exposure, provides a theoretical basis for developing an iNOS-targeted inhibitor, and also provides a new target for etiological recognition, early diagnosis and prevention of related diseases caused by environmental toxin combined exposure.

The invention belongs to the technical field of cytotoxicity intervention, and particularly relates to application of an inhibitor JSH-23 in preparation of a medicine for preventing and / or treating ovarian toxicity caused by environmental toxin combined exposure. Aiming at the condition that MC-LR and NaNON combined exposure can activate NF-kappa B to induce KK-1 cell nitrification stress and cause mouse ovarian dysfunction, JSH-23 is selected as an intervention agent, and it is found that after KK-1 cells are pretreated by JSH-23, NF-kappa B nuclear translocation induced by the KK-1 cells due to MC-LR and NaNON combined exposure is remarkably inhibited, iNOS protein rising induced by toxin combined exposure is remarkably reduced, and NF-kappa B nuclear translocation induced by the KK-1 cells due to NF-kappa B combined exposure is remarkably inhibited. The increase of the levels of ONOO and 3-NT of nitration stress markers is effectively relieved, which indicates that JSH-23 can participate in the nitration stress of KK-1 cells caused by combined exposure of MC-LR and NaNO2 by inhibiting NF-kappa B activation, and a foundation is laid for screening antidotes after exposure of environmental toxins.

The invention relates to the technical field of genetic engineering and biological agents, in particular to a hybrid peptide with immunoregulation and anti-oxidation functions and a preparation method and application of the hybrid peptide. The polypeptide provided by the invention has immunoregulation and antioxidation functions at the same time, and in a normal or immunosuppression state, the polypeptide can significantly improve the immunologic function of a body and reduce the damage of immunosuppression to the body; the oxidation resistance of cells and organisms can be enhanced; meanwhile, the polypeptide has the advantages of low cytotoxicity, high safety, simplicity and convenience in preparation and low cost, can be used as an ideal immunomodulator and an antioxidant, is widely applied to the fields of medicines, foods, health care, feeds, nutrition and the like of human and animals, and has very good application potential and value.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

The invention relates to the technical field of pharmaceutical preparations, and provides double-shell JAK inhibitor nanoparticles, a preparation method thereof and targeted delivery eye drops. The double-shell JAK inhibitor nanoparticle provided by the invention comprises a core, an inner shell and an outer shell, wherein the core comprises a nanostructure lipid carrier and a JAK inhibitor; the inner shell layer is a cationic polymer, and the outer shell layer is hyaluronic acid. Through the design of the positive charge inner shell layer and the negative charge outer shell layer, the dual functions of mucosa adhesion and active targeting are achieved, the surface of the nanoparticle is electronegative finally, cytotoxicity possibly caused by direct exposure of a cationic polymer is reduced, non-specific aggregation of the cationic polymer and electronegative protein in tears is avoided, and the stability of tears is improved. And the stability of the preparation is improved. The eye drops provided by the invention can obviously prolong the residence time of the JAK inhibitor on the ocular surface, enhance the cornea permeability, can actively target to ocular inflammatory cells, and have a wide application prospect.

The invention belongs to the technical field of biological medicines, and particularly discloses a nano-engineering T cell membrane coated nano-particle as well as a preparation method and application of the nano-engineering T cell membrane coated nano-particle. Nanoparticles of a specific structure are constructed based on a phospholipid bilayer bionic nanometer platform through a membrane fusion technology, immune clearance caused by phagocytosis of the nanoparticles by macrophages can be avoided through disguise of a T cell membrane, and the blood circulation time is prolonged; the functions of T cells are recovered through specific blocking of immune checkpoint molecules loaded on the immune checkpoint molecules on corresponding immune checkpoint ligands on tumor cells; under ultrasonic radiation, the nano-particles are gradually decomposed and release the sound-sensitive agent to generate a large amount of active oxygen, so that immunogenic death of tumor cells is promoted, more cytotoxic T lymphocytes are recruited to infiltrate into tumor parts, and the recovery of T cell mediated immune response function is facilitated. The synergistic effect of the sound-sensitive agent and the immune checkpoint protein can effectively inhibit tumor growth, induce a long-term immune memory effect and prevent tumor metastasis and recurrence.

The invention belongs to the technical field of biological medicine, and particularly relates to application of anethomycin in preparation of medicine for inhibiting cysteine protease activity. The invention discovers that anethomycin has the function of inhibiting the activity of virus cysteine protease, especially 3C or 3CL protease, for the first time. Molecular docking proves that anethomycin can effectively bind to the catalytic activity center of Senecavirus (SVA) 3C protease. An in-vitro FRET enzyme activity experiment proves that the inhibition rate of 50 [mu] M of anethomycin on SVA 3C protease reaches up to 88.5%. Cellular level experiments show that the anethomycin can significantly inhibit replication of SVA viruses, shows broad-spectrum antiviral activity on various viruses such as encephalomyocarditis viruses (EMCV), porcine reproductive and respiratory syndrome viruses (PRRSV) and porcine deltacoronaviruses (PDCoV), and is low in cytotoxicity and high in selectivity index (SI).

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

The invention discloses a modified melittin peptide, a product containing the modified melittin peptide and application, and belongs to the technical field of biological medicine. The amino acid sequence of the modified melittin is shown as Seq ID No: 2, the molecular weight of the modified melittin is 3123.5 Da, and the isoelectric point of the modified melittin is 12.64. The invention further discloses application of the modified melittin peptide in preparation of drugs or cosmetics for inhibiting inflammation and relieving skin erythema and itching. The invention also discloses application of the modified melittin peptide in preparation of drugs or cosmetics for enhancing cell activity and promoting tissue repair. The melittin modified peptide can significantly reduce the cytotoxicity of natural melittin and significantly enhance the anti-inflammatory activity and tissue repair activity of the melittin, has no sensitization and phototoxicity, and can provide key technical support for research and development of new-generation efficient and safe anti-inflammatory repair drugs, cosmetic products and related biological materials.

The invention discloses a nano compound based on a CRISPR-Cas9 system and application of the nano compound. The nano compound comprises a histidine oligopeptide-cell penetrating peptide conjugate and an RNP compound composed of sgRNA of a target gene and Cas9 protein, and the histidine oligopeptide-cell penetrating peptide conjugate and the RNP compound are self-assembled under the action of zinc ions to form the nano compound. The nano-composite designed by the invention is simple in structure, and overcomes the defects of high cytotoxicity and large particle size (diameter gt; compared with the prior art, the compound has the advantages that the compound can overcome the defects of complex chemical synthesis, potential immunogenicity and the like, can be used for extracellular-cytoplasm-cell nucleus trinity antivirus, is high in virus removal efficiency and good in antivirus effect, and has high market value and development potential.

The invention discloses a QS-21 composite adjuvant and a preparation method thereof, and belongs to the technical field of biological medicines. According to the QS-21 composite adjuvant, a polyanion material and QS-21 are compounded to form nanoparticles, and the nanoparticles are organically combined with a freeze-drying protective additive, so that the prepared QS-21 composite adjuvant is relatively high in retention rate, the problems of hydrolysis and oxidation are solved, the requirement of a phospholipid carrier is avoided, and a vaccine co-preparation process is simplified; the subsequently added freeze-drying protective agent retains the immune enhancement activity of the QS-21 and reduces the exposure of the QS-21 to a degradation environment; the corresponding cytotoxicity meets the standard, and the hemolysis rate is low; therefore, the method has remarkable clinical application value and industrialization potential.

Provided are chemically modified silk fibroin and a use thereof in cell and organoid culture. The chemically modified silk fibroin is a product obtained by sequentially carboxylating silk fibroin and modifying same by an organic amine having a phenol group. Also provided is a hydrogel based on the chemically modified silk fibroin. A hydrogel system has a hierarchical structure and mechanical properties similar to those of an extracellular matrix, and exhibits characteristics such as definite composition, controllable physicochemical properties, low cytotoxicity, good biocompatibility, and biodegradability, can support the growth and differentiation of cells and organoids, and is suitable as a matrigel for cell and organoid culture.

The invention discloses a nucleic acid transfection system and method based on automatic control, and relates to the technical field of genetic engineering.The method comprises the steps that after target cells are intelligently cultured to be in a suitable state, an automatic system selects a transfection reagent and prepares a compound according to cell types; the cells and the compound are mixed through low shear force and then incubated; multi-modal monitoring equipment is used for tracking nucleic acid distribution and cell states in real time, and incubation conditions are dynamically adjusted; analyzing the monitoring data based on a machine learning algorithm and optimizing transfection parameters; after transfection, culture and multi-dimensional analysis are automatically executed. The system correspondingly comprises a cell culture module, a reagent preparation module, a mixed incubation module, a real-time monitoring module, a dynamic optimization module and a subsequent analysis module. Through closed-loop automatic control and intelligent optimization, the transfection efficiency and stability are remarkably improved, the cytotoxicity is reduced, manual intervention is reduced, and a standardized solution is provided for recombinant gene expression.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture, through the repeated co-culturing of NK cells with feeder cells and the selective use of stimulatory interleukins. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, which results in a highly expanded and highly cytotoxic population of cells, for use in, for example allogeneic cellular immunotherapy.

Disclosed herein are systems, methods, and compositions for treating a subject diagnosed with, or suffering from cancer. In some embodiments, the method comprises determining whether a tumor sample from the subject includes a cytotoxic gene signature, and treating the subject based on the determination. In some embodiments, the subject has or is suspected of having a loss of heterozygosity in human leukocyte antigen (HLA) class I genes. In some embodiments, the therapy comprises one or more checkpoint inhibitors. In some embodiments, the cancer is colorectal, uterine, stomach, lung, skin, head or neck, or non-small cell lung carcinoma.

A recombinant NK-92 cell has a constitutive active promotor that effects expression of native CD16, and most preferably homogenous CD16 158V. Further contemplated recombinant NK-92 cells also include a recombinant nucleic acid that encodes an intracellularly retained interleukin (e.g., IL-2 or er-IL-2), wherein the recombinant NK-92 cell will secrete no more than 5,000 pg / mL IL-2 into a culture medium. The recombinant NK-92 cells presented herein have a significantly improved signal-to-noise ratio and exhibit reduced non-ADCC cytotoxicity.

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.

An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

The invention discloses a nanofiber based on a polypeptide derivative and an enzymatic self-assembly method and application of the nanofiber based on the polypeptide derivative, the sequence of the polypeptide derivative is Nap-Gly-Phe-Phe-pTyr-Lys-Trp-Tyr-Gln-Asn-Met-Ile-Arg, and the Gly-Phe-Phe-pTyr is of an L configuration or a D configuration. The self-assembled polypeptide derivative disclosed by the invention contains an alkaline phosphatase restriction enzyme cutting site, and the self-assembled polypeptide derivative is self-assembled at a specific part with high enzyme specificity expression through enzyme catalysis to form nanofibers. The nanofiber hydrogel obtained through enzymatic treatment is carried out under physiological conditions, high temperature or ultraviolet irradiation is not needed, damage of high temperature to bioactive substances is avoided, the nanofiber hydrogel is more suitable for a temperature-sensitive in-vivo environment, toxic chemical cross-linking agents or photoinitiators do not need to be introduced, the cytotoxicity of the material is remarkably reduced, active enzymes or drugs can be embedded in situ, and the nanofiber hydrogel can be used for in-situ treatment. The biological function is maintained.

The invention relates to the technical field of thrombus mining robots, in particular to a micron robot with an asymmetric cilia structure, a preparation method and application. The micro-robot is of an asymmetric composite structure and is composed of a smooth hemisphere and a cilia-shaped structure, sandwich type layered arrangement of a PLGE cilia-shaped nano structure, an MNPs interlayer and a PS sphere core is formed on the surface and the interior of the micro-robot from outside to inside, and cooperative regulation and control of morphology and functions are achieved by regulating and controlling the material proportion of PS and PLGE. The thrombus mining robot shows an efficient thrombolysis effect in a plurality of in-vitro and in-vivo models, and rapid fibrinolysis, deep thrombus penetration and efficient mining of single red blood cells are realized, so that the limitation of a traditional thrombolysis agent is overcome. In addition, the thrombus digging robot has excellent biocompatibility and biological safety, has no obvious cytotoxicity or damage to main organs, and supports the safety of the thrombus digging robot in clinical application.

The invention belongs to the technical field of biological medicine, and particularly discloses nano composite particles based on a metal organic framework and a preparation method and application of the nano composite particles. The nano-composite particles are constructed through electron adsorption and coordination based on a nano-scale metal organic framework, and under the acidic microenvironment and ultrasonic irradiation of tumors, the nano-composite particles can be decomposed and released in a responsive manner, play a role of a sound-sensitive agent, generate a large amount of active oxygen and induce tumor cells to generate immunogenic death, so that the tumor cell immunogenicity is improved, and the tumor cell immunogenicity is improved. Further, more cytotoxic T lymphocytes are promoted to infiltrate a tumor microenvironment, T cell mediated anti-tumor immune response is recovered, and tumor metastasis is effectively prevented. The carrier metal organic framework ZIF8 of the nano-composite particles can serve as a sound-sensitive agent to generate active oxygen, the function of ultrasonic imaging of tumor tissue can be achieved, the effect of diagnosis is achieved while treatment is conducted, tumor diagnosis and treatment monitoring can be achieved at the same time through one-time drug administration, and a new strategy is provided for precise medical treatment.

The invention discloses a gamma delta T cell efficient amplification method and application, and belongs to the technical field of cell biology. The amplification method comprises the following steps: separating PBMC (peripheral blood mononuclear cells) by adopting a density gradient centrifugation method, carrying out initial culture through a polylysine coated container, carrying out three-stage dynamic stimulation, combining with an X-VIVO 15 culture medium of 5-8% autoserum, and finally carrying out anti-gamma delta TCR magnetic bead separation to obtain high-purity cells. Through collaborative optimization of stepped factor combination, staged container coating and a low-serum system, the amplification multiple of the gamma delta T cells reaches 150-180 times, the purity is larger than or equal to 90% after purification, the cytotoxicity and the survival ability are remarkably improved, the gamma delta T cells can be efficiently used for immunotherapy of tumors and infectious diseases, and stable technical support is provided for clinical transformation of the gamma delta T cells.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

This invention discloses a protein-polysaccharide ternary nanoparticle loaded with cordycepin, its preparation method, and its applications. The invention employs a layer-by-layer self-assembly method to modify the surface of zein nanoparticles. Since zein has a positive surface charge, the first layer modification uses the anionic polysaccharide sodium alginate for electrostatic bonding, and the second layer modification uses the cationic polysaccharide chitosan, constructing positively charged ternary composite nanoparticles. These nanoparticles have small particle size, high encapsulation efficiency, high drug loading capacity, and a sustained-release effect, significantly reducing cytotoxicity and significantly improving the therapeutic effect on osteoarthritis. This invention develops a novel cordycepin formulation, overcoming the limitations of cordycepin's clinical use.

The invention provides an amino acid skeleton ionizable lipid as well as a preparation method and application thereof, the amino acid skeleton ionizable lipid is modified by taking amino acid as a core, has more ester groups and peptide bonds, and can be quickly hydrolyzed by enzyme after RNA is effectively released in vivo; the transfection body is provided with four tail structures, the cross sectional area of the lipid tail can be increased, drugs such as RNA are helped to escape from an endosome, and then the transfection effect is enhanced; the charge capable of ionizing the lipid is electrically neutral under physiological conditions, so that the cytotoxicity caused by excessive positive charges is reduced, the stability of the lipid nanoparticles is further improved, the cycle time of the loaded nucleic acid medicine is prolonged, and the pharmacokinetic characteristics are improved. The LNP prepared from the ionizable lipid, auxiliary phospholipid, cholesterol and PEG lipid provided by the invention has more excellent nucleic acid carrier performance, and can effectively deliver nucleic acid drugs such as siRNA, mRNA, pDNA and the like into cells to play a role.

Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen / LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

The invention relates to a 5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound as well as a preparation method and medical application thereof. The compound is efficiently synthesized through Ullmann coupling and palladium-catalyzed intramolecular arylation reaction. In-vitro anti-tumor activity research shows that the compound has remarkable selective inhibitory activity on various human tumor cell lines, and particularly, the inhibitory effect on non-small cell lung cancer A549 cells (IC50 = 0.21 mu M) is improved by two orders of magnitude compared with that of cis-platinum; iC50 (half maximal inhibitory concentration) of other cell lines are as follows: 1.26 mu M of prostate cancer PC-3 cells, 6.78 mu M of liver cancer HepG2 cells, 7.99 mu M of cervical cancer Hela cells and 25.46 mu M of breast cancer MCF-7 cells. Preliminary toxicity experiments prove that the compound has the characteristic of low cytotoxicity. The compound can be used as a novel high-efficiency low-toxicity anti-tumor lead compound, and provides an important structural basis for the development of anti-cancer drugs.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors as well as genetically edited or otherwise engineered enhance the persistence the cells in immunotherapy. In several embodiments, the cells are edited to knock out a target gene that encodes a protein involved in antigen processing and presentation by major histocompatibility complex class I molecules. In several embodiments, a mixture of immune cell types is used, optionally in allogeneic therapy. The engineering and editing of the cells, such as NK cells and / or T cells exhibit enhanced cytotoxicity and / or persistence, as well as reduced risk of reduced graft versus host, host versus graft, and graft versus graft effects.