604 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.

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 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).

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.

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.

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.

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.

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.

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.

The present invention relates to a compound represented by formula (I) or a stereoisomer, tautomer, solvate or pharmaceutically acceptable salt of a compound represented by formula (I), TIFF2026503201000033.tif3981X1, X2 and X3 are each independently an optionally substituted C1-C 15 alkylene, and R and R are each independently an optionally substituted C-C 40 Alkyl, optionally substituted C-C 40 Heteroalkyl, optionally substituted C-C 40 Alkenyl, optionally substituted C-C 40 Heteroalkenyl, optionally substituted C-C 40 Alkynyl or optionally substituted C-C 40 The present invention provides a compound comprising heteroalkynyl, wherein R3, R4, R5, and R6 are each independently H, halogen, or optionally substituted C1-C3 alkyl, and the substituents are independently selected from halogen, -OH, -SH, -NH2, -NO2, cyano, and C1-C3 alkyl, which has the advantages of low cytotoxicity, strong delivery ability, and strong immunostimulatory effect.

The invention discloses application of fluorinated ionizable lipid as a gene drug delivery carrier, and belongs to the technical field of biological medicine. The gene drug delivery carrier provided by the invention is prepared from fluorinated ionizable lipids, cationic lipids, auxiliary lipids, structural lipids and PEG lipids, wherein the molar percentage of the fluorinated ionizable lipids in the gene drug delivery carrier is 1%-10%. According to the invention, the molar percentage of the fluorinated ionizable lipid in the total lipid is optimized to 1-10%, so that the cytotoxicity is obviously reduced, and more excellent nucleic acid transfection efficiency is realized in vivo and in vitro; various nucleic acid drugs including DNA, mRNA, siRNA and CRISPR-Cas9 ribonucleoprotein can be efficiently delivered, action targets of the nucleic acid drugs are expanded to cell nucleuses and cytoplasm, and the nucleic acid drugs are more accordant with the action mechanism of modern gene therapy and editing.

Methods of treating colon cancer with antibodies that specifically bind to human cytotoxic T-lymphocyte antigen 4 (CTLA-4) are provided.

The present invention relates to canine antibodies, binding polypeptides, and scFvs specific for canine cytotoxic T lymphocyte associated protein 4 (CTLA-4).

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

The invention relates to the technical field of biochemistry, and particularly discloses a galactosyl zinc-porphyrin derivative and a preparation method and application thereof.The galactosyl zinc-porphyrin derivative is formed by coupling a group with double functions of fluorescence and cytotoxic activity and a liver cancer targeting group, can be specifically combined with a liver cancer cell HepG2, emits 608 nm and 659 nm fluorescence signals under the excitation wavelength of 425 nm, and can be used for detecting liver cancer. And accurate tracing can be realized. Meanwhile, IC509.1 mu M + / -2.59 is used for killing liver cancer cells, so that targeted therapy is realized. The chemical disclosed by the invention has the functions of fluorescence tracing and targeted killing, can synchronously realize accurate positioning (fluorescence tracing) and efficient removal (targeted treatment) of liver cancer cells without drug combination, can be used for liver cancer diagnosis, treatment and curative effect evaluation, and has extremely high research and development value.

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

The invention provides a DNA (Deoxyribose Nucleic Acid) nano-structure carrier. The DNA nano-structure carrier provided by the invention has an EGFR (epidermal growth factor receptor) aptamer structure and is used for loading a connecting sequence of siRNA; moreover, after the siRNA is loaded, the DNA nano-structure carrier can further load a chemotherapeutic drug such as adriamycin, so that a DNA nano-drug based on the DNA nano-structure carrier is obtained. Through the target gene expression knock-down effect of siME3, the cytotoxicity of adriamycin and the targeting property of the EGFR aptamer structure, the DNA nano-drug provided by the invention can effectively inhibit pancreatic cancer, especially the growth of ME2 deletion type pancreatic cancer cells.

The invention relates to the technical field of anti-cancer chemical drugs, in particular to a thiadiazole tetranuclear copper complex with anti-tumor and antibacterial activity and a preparation method and application of the thiadiazole tetranuclear copper complex. The chemical formula of the complex is [Cu4 (C3H3S2N2) 2 (C3H4S2N2) 4], the complex is synthesized from ligand thiadiazole and CuX, X is I or Br, and copper in the obtained complex is + 1 valence. The complex shows a good cytotoxic effect on breast cancer cells MCF-7, is likely to play a toxic effect by inducing apoptosis, ferroptosis, copper death and other ways, has a good antibacterial effect, has potential medicinal value, and is expected to be developed into a new generation of anti-tumor drugs with antibacterial properties.

The invention provides an application of combination of SPRC and a PD-1 or PD-L1 inhibitor in preparation of a lung cancer immunotherapy sensitizing drug, and relates to the technical field of biomedicine.In the application, through in-vitro cell experiments, cell co-culture experiments and in-vivo animal experiments, S-propargyl-L-cysteine (SPRC) can play a sensitizing role in the anti-lung cancer curative effect of the PD-1 inhibitor, and can be used for preparing a sensitizing drug for lung cancer immunotherapy. The core mechanism is as follows: 30 [mu] M SPRC is in a non-cytotoxic dose window and can specifically inhibit IFN-gamma induced STAT1 phosphorylation and PD-L1 up-regulation by depending on a CSE / H2S pathway, while IFN-gamma-STAT1-PD-L1 is a core signal axis of PD-L1 adaptive up-regulation in lung cancer cells, and the induction effect of TNF-alpha on PD-L1 is relatively weak; meanwhile, SPRC can inhibit activation of NF-kB induced by TNF-alpha and expression of inflammatory factors such as IL-6 and IL-8 through the pathway so as to exert the anti-inflammatory effect, the CD8 + T cell depletion proportion can be remarkably reduced by combining SPRC with anti-PD-1, the synergistic tumor inhibition effect is formed, the effect is verified in in-vivo and in-vitro experiments, and a closed loop of an in-vitro mechanism and an in-vivo curative effect is achieved.

The present invention relates to a modified mitochondrial comprising, on the outer membrane of the mitochondrial, an antibody that binds to a cancer cell-specific protein and a cytosine deaminase. It is proved that when the mitochondria and 5-FC are jointly used for treating a pancreatic cancer cell line, the cytotoxicity induced by 5-FC treatment is remarkably enhanced. The effect is proved as follows: 5-FC is converted into 5-FU by cytosine deaminase expressed on a mitochondrial outer membrane, so that pancreatic cancer cells are induced to generate apoptosis. Therefore, the modified mitochondria according to the present invention can be effectively used in anticancer therapy using 5-FC as an anticancer agent.

The invention relates to a bispecific antibody-cytokine fusion protein as well as a preparation method and application thereof. The fusion protein comprises a TAA binding unit, a T cell binding unit and a cytokine unit, the TAA binding unit comprises an anti-HER2 structural domain, the T cell binding unit comprises an anti-CD3 structural domain, and the cell factor unit comprises IL-2; the anti-CD3 structural domain and the IL-2 structural domain can act on T cells at the same time, further amplification of the T cells is promoted while the T cells are activated to generate cytotoxic killing, the anti-CD3 structural domain and the IL-2 structural domain can be directionally migrated to the periphery of HER2 positive tumor cells through the anti-HER2 structural domain, the efficiency of promoting proliferation and differentiation of tumor infiltrating T cells is improved, and the T cells can be effectively degraded. The effect of killing solid tumor cells by immune cells is greatly improved, the non-specific killing effect of the fusion protein on normal cells and the accompanying release of cytokines in peripheral blood can be reduced to the minimum, and the toxic and side effects of the fusion protein in clinical treatment are reduced.

This invention belongs to the field of biomedical technology, specifically relating to a compound extracted from *Acer buergerianum* (a type of shrub), its extraction method, and its application in the preparation of drugs for the prevention or treatment of non-alcoholic fatty liver disease. This invention is the first to obtain a natural compound with a novel structure from *Acer buergerianum*, and provides a method for its preparation. Activity studies were conducted, and experimental data show that the compound exhibits low cytotoxicity and no significant cytotoxicity to normal cells. It can inhibit the expression of fatty acid synthases ACC, ACLY, and FAS, thereby inhibiting de novo fatty acid synthesis in cells, suppressing lipid droplet accumulation, and reducing cellular lipid levels. This compound has broad application prospects in the preparation of drugs for the prevention or treatment of non-alcoholic fatty liver disease.

The present invention relates to a medium composition for in vitro fertilization and / or in vitro culture comprising a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof, and a method using same. The compound or composition suppresses reactive oxygen species and lipid peroxidation in ovarian granulosa cells to preventing cytotoxicity and mitochondrial dysfunction caused by apoptosis and ferroptosis, leading to an improvement in the quality of aged oocytes, and to increase the developmental rate and blastocyst formation rate of pre-implantation embryos, thereby improving the efficiency of in vitro fertilization. In addition, treatment with the medium composition during the vitrification process of in vitro–fertilized embryos improves re-expansion and survival rates, thereby reducing structural and metabolic damage. Accordingly, the present invention can be advantageously applied to an assisted reproductive technology for treating infertility and subfertility, and in vitro fertilization and / or in vitro culture for improving the propagation efficiency of livestock.

Novel kisspeptin-13 or KP-13 peptides and KP-13 satellites or modified peptides (KPSATs) are disclosed having improved therapeutic benefits in regulating pathophysiological changes in various tissues, particularly lung tissue. These KPSATs have improved antiproliferative effects and non-cytotoxic effects on airway smooth muscle cells and tissue.

The application discloses a compound containing a 3-alkynyl pyrrole structure and application thereof. The compound containing the 3-alkynyl pyrrole structure provided by the application is confirmed to have a down-regulation effect on inflammatory factors secreted by LPS-induced primary alveolar macrophages through cell experiments, and has no obvious cytotoxicity. The application provides a new treatment strategy for clinical acute lung injury (ALI) treatment.

The invention discloses application of a small molecule compound in preparation of a medicine for treating ovarian cancer, and belongs to the technical field of biological medicine. The small molecule compound comprises a structure as shown in a formula (I) or an isomer, a pharmaceutically acceptable solvate or salt thereof, it is found for the first time that the small molecule compound can effectively reduce protein expression of YBX1, and meanwhile in-vitro verification experiments prove that the small molecule compound has a remarkable inhibition effect on proliferation of ovarian cancer cells. In addition, it is found that the small molecule compound can improve the cytotoxicity of cis-platinum and significantly enhance the anti-tumor effect of cis-platinum. The application of the small molecule compound YB-B1 targeting YBX1 in preparation of the medicine for treating the ovarian cancer is disclosed for the first time, a new method and a new idea are provided for clinical treatment of the ovarian cancer, and the small molecule compound YB-B1 particularly has remarkable significance in auxiliary treatment and prevention and treatment of cis-platinum drug-resistant ovarian cancer.

The present application relates to azapeptide compounds of formula (I) derived from melanocyte-stimulating hormone release-inhibiting factor-1. A method to obtain compounds of formula (I) is also described herein. The compounds of formula (I) have been shown to be suitable for the treatment of dopamine-related disorders of the central nervous system. These compounds showed enhanced potency as positive allosteric modulators of the dopamine D2 receptors in comparison with the melanocyte-stimulating hormone release- inhibiting factor-1 and, in general, do not exhibit meaningful cytotoxicity.

Provided herein are novel exosomal compositions that exhibit cytotoxicity and method of treating cancer that utilize such exosomal compositions.

The present invention relates to a cytotoxic agent for the prophylaxis and / or treatment of a viral infection which is configured for the selective binding to a membrane receptor of virus-infected T lymphocytes, a pharmaceutical composition containing said cytotoxic agent, the use of the cytotoxic agent for the prophylaxis and / or treatment of viral infections, a method of finding cytotoxic agents, the use of a membrane receptor of virus-infected T lymphocytes which is overexpressed in comparison to non-infected T lymphocytes for the diagnosis of a viral infection.