24 results about "Cell cytotoxicity" patented technology

A method for reprogramming native CD4+ T-cells is provided. The method comprises incubating the CD4+ T-cells with a Class 1 HDAC inhibitor for a period of time sufficient to increase cytotoxicity of the CD4+ T-cells in comparison to the cytotoxicity of native CD4+ T-cells. The method may be utilized to prepare cytotoxic tumor infiltrating CD4+ T-cells for use to treat cancer, including MHC-I deficient cancers.

The present inventors discovered novel multispecific antigen-binding molecules with excellent cellular cytotoxicity, which comprise a first domain comprising a first antigen variable region which binds to DLL3 and a second domain comprising a second antigen variable region which binds to T cell receptor complex. The present inventors prepared further bispecific antibodies, and assessed their T cell-dependent cell cytotoxicity (TDCC), and found that they also show strong TDCC activity. Since the molecules / antibodies of the present invention show a strong cytotoxicity against cells expressing DLL3, novel pharmaceutical compositions comprising the molecules / antibodies for treating or preventing various cancers associated with DLL3 can be provided.

The application discloses a new use of androsta-4,6,8(9),13(14)-tetraen-3,11,16-trione, namely, application of the androsta-4,6,8(9),13(14)-tetraen-3,11,16-trione in preparation of a medicine for treating lymphoma. 50 The IC value of the androsta-4,6,8(9),13(14)-tetraen-3,11,16-trione in the SR cell line is detected by a CCK-8 method, and the cytotoxicity of the androsta-4,6,8(9),13(14)-tetraen-3,11,16-trione on human umbilical vein endothelial cells Huvce and human immortalized keratinocytes Hacat is detected, in the body, the androsta-4,6,8(9),13(14)-tetraen-3,11,16-trione significantly inhibits tumor growth and shows good biological safety and no systemic toxicity; TUNEL staining, gamma-H2AX staining and neutral comet experiment prove that the compound of the application inhibits the growth of SR by causing serious damage to DNA, the application not only adds the diversity of the biological activity of the androsta-4,6,8(9),13(14)-tetraen-3,11,16-trione, but also provides a new direction for developing a new medicine for treating lymphoma.

This invention discloses an antimicrobial peptide, its pharmaceutical composition, and its applications. The invention optimizes the structure of the antimicrobial peptide through deuteration modification technology, significantly enhancing its targeted binding ability to β-1,3-D-glucan synthase. The affinity of this antimicrobial peptide for the aforementioned target is 9-27 times that of the control peptide. In vitro assays show that its minimum inhibitory concentration (MIC) against nine standard Candida strains is consistently 0.002 μg / mL, exhibiting significantly superior activity compared to fluconazole, anidoxurine, and the control peptide. It also exhibits extremely low cytotoxicity against L02 human normal hepatocytes. In in vivo experiments, in a neutropenic mouse model of Candida albicans infection, the antimicrobial peptide at all doses showed superior reduction in renal fungal load compared to anidoxurine and the control peptide. The antimicrobial peptide of this invention combines highly efficient anti-Candida activity, low cytotoxicity, and excellent in vivo efficacy, providing a safe and effective candidate drug for the treatment of drug-resistant candidiasis and possessing good clinical translational value.

A synthetic cytokine signaling system comprises an engineered cytokine signaling chain encoding a transmembrane polypeptide containing a specific variant intracellular domain of IL9R and an extracellular domain of cytokine receptors such as IL2R [beta], IL4R [alpha], IL7R [alpha], IL9R and IL21R. The engineered cytokine signal chain may be in a self-activating form, or optionally may be in a non-self-activating form, depending on whether the functionally compatible cytokine ligand domain is fused to the N-terminus. In the latter case, the synthetic cytokine signaling system may further comprise an engineered cytokine ligand chain that encodes a corresponding cytokine ligand, which may be membrane-bound or secreted. Immune cells modified with the synthetic cytokine signaling system exhibit improved properties compared to unmodified immune cells, such as zero or reduced dependency on IL-2 when cultured in vitro, enhanced activation after antigen stimulation, enhanced cytotoxicity to target cells, and improved tumor control ability when metastatic in vivo.

The present disclosure relates to tetrahydroquinazoline derivatives of formula (I) and their use for selectively killing GAG-POL expressing cells infected by HIV without accompanying cytotoxicity on HIV primordial cells, and for treating or preventing HIV infection, or for treating, preventing or delaying the onset or progression of AIDS or AIDS-related syndrome (ARC). (I).

Methods and compositions are provided for generating cytokine-induced memory-like (CIML) phenotypes in NK-92-derived cell lines including activated NK (aNK) and PD-L1 chimeric antigen receptor NK (PD-L1 t-haNK) cells. Brief exposure of the cells to interleukin-12, interleukin-18, and the interleukin-15 (or interleukin-15 superagonist N-803) induces durable interferon-gamma expression and a memory recall response that persists for at least a week after stimulation. The disclosure includes methods for manufacturing, irradiating, and cryopreserving CIML aNK and CIML t-haNK cell products that provide a standardized off-the-shelf therapy for the targeted treatment of cancers, including tumors that are initially resistant to NK-cell cytotoxicity.

Disclosed herein include methods, compositions, and kits suitable for use in enhancing adoptive T cell therapy. In some embodiments, the method comprises contacting isolated organelle complexes with a population of T cells to generate a population of T cells comprising the organelle complexes. The organelle complexes can comprise mitochondria and one or more of endoplasmic reticulum, peroxisomes, lysosomes, and Golgi apparatus. The population of T cells can exhibit one or more of enhanced expansion capability, enhanced cytotoxicity against target cells, enhanced resistance to exhaustion, and enhanced persistence, as compared to a population of T cells that do not comprise exogenous organelle complexes

The invention relates to an application of bifidobacterium animalis subsp. Lactis BLa80 in preparation of a preparation for improving Parkinson's disease. The bifidobacterium animalis subsp. Lactis BLa80 is a strain of the bifidobacterium animalis subsp. Lactis BLa80 with the preservation number of CGMCC (China General Microbiological Culture Collection Center) No.22547, and the strain of the bifidobacterium animalis subsp. Lactis BLa80 is a strain of the bifidobacterium animalis subsp. Lactis BLa80 with the preservation number of CGMCC No.22547. The brand new application of the BLa80 strain of the animal bifidobacterium subsp. Lactis is developed, namely the BLa80 strain is used for improving the Parkinson's disease, specifically, the BLa80 strain can weaken the cytotoxicity of 6-OHDA induced SH-SY5Y cells, relieve weight loss of MPTP induced subacute Parkinson's disease model mice, relieve dyskinesia of the mice and improve the Parkinson's disease. According to the present invention, the mice are subjected to the mouse striatum activation, such that the dopaminergic neuron is protected, the dopamine content in the mouse striatum is increased, the intestinal inflammation is relieved, the ratio of the thick-wall mycophylum to the bacteroides in the mouse intestinal flora is increased, the intestinal beneficial flora abundance is improved, and the intestinal flora diversity is increased;

The application relates to application of Astragalus polysaccharide in colon cancer drugs by regulating intestinal flora, and extracts crude polysaccharide (ARCP) in Astragalus, which can be used for drugs for treating or preventing colon cancer, and the ARCP realizes the effect on colon cancer mainly by regulating intestinal flora; the ARCP can increase the proportion of CD8 + T cells, improve the tumor immune microenvironment, regulate T cell subgroups, the ARCP has the ability of up-regulating Tem subgroup, down-regulating Temra subgroup, making Tem the dominant subgroup, thereby increasing the cytotoxicity of CD8 + T cells, and improving the killing ability on tumor cells.

Methods and compositions are provided for generating cytokine-induced memory-like (CIML) phenotypes in NK-92-derived cell lines including activated NK (aNK) and PD-L1 chimeric antigen receptor NK (PD-L1 t-haNK) cells. Brief exposure of the cells to interleukin-12, interleukin-18, and the interleukin-15 (or interleukin-15 superagonist N-803) induces durable interferon-gamma expression and a memory recall response that persists for at least a week after stimulation. The disclosure includes methods for manufacturing, irradiating, and cryopreserving CIML aNK and CIML t-haNK cell products that provide a standardized off-the-shelf therapy for the targeted treatment of cancers, including tumors that are initially resistant to NK-cell cytotoxicity.

The present disclosure relates to compositions and methods for treating cancers (e.g., ovarian cancer) or increasing cytotoxicity of T cells by modulating expression, level, and / or activity of Transgelin-2 (TAGLN2) in T cells. It also discloses vectors to increase expression, level, and / or activity of TAGLN2 in T cells, T cells co-expressing a CAR and TAGLN2, and adaptive cell therapies using such T cells. Methods of assessing functional status and / or anti-tumor activity of T cells using TAGLN2 as a biomarker are also disclosed.

The application relates to the technical field of metal organic complexes, in particular to a chiral Au 16 Metal complex and preparation method and application thereof. By using a specific chiral 1,4-di (dithiocarbamate) -2-methyl piperazine potassium salt ligand, a specific chiral Au 16 Metal complex, 16 Au atoms in the structure of the metal complex form an Au 16 Macrocycle, 16 gold atoms form a polynuclear gold compound, and the chiral Au 16 Drug activity of the metal complex on cancer cells. In in-vitro cell experiments, the chiral Au 16 The metal complex has good in-vitro anticancer activity in different cancer cell lines. Meanwhile, due to the Au-Au bonding, a macrocycle structure is formed, and the chiral Au 16 Cytotoxicity of the metal complex on normal cells.

Provided herein are compositions and methods for detecting migration of effector cells towards a target cell, and cytotoxicity of the migrated effector cells against the target cells. The effector cells are modified to express a homing or migratory receptor, and the target cells are modified to express the cognate ligand. The methods can be carried out in a Boyden chamber or tranwells with a porous membrane between the wells. The membrane can be coated with an extracellular matrix component to simulate a solid tumor environment.

Provided herein is a cytotoxic compound that targets cells. Such compounds can be used to selectively bind to and kill cancer cells, such as cancer stem cells that express LGR4, LGR5, or LGR6. In some embodiments, the cytotoxic compound comprises an LGR-binding polypeptide, a cytotoxic agent (e.g., MMAE), and an Fc region (e.g., a mutant Fc domain). Also provided is a method for using the compound to treat cell proliferation diseases, such as cancer. TIFF2026503181000087.tif105146

The invention discloses an antibacterial peptide as well as a pharmaceutical composition and application thereof. The structure of the antibacterial peptide is optimized through a deuterated modification technology, and the targeted binding capacity of the antibacterial peptide to beta-1, 3-D-glucan synthetase is remarkably improved. The affinity of the antibacterial peptide to the target spot is 9-27 times that of a control peptide; in-vitro determination shows that the minimum inhibitory concentration (MIC) of the compound to nine standard candida strains is stabilized to be 0.002 mu g / mL, and the activity of the compound is remarkably superior to that of fluconazole, anidulafungin and control peptide; the cytotoxicity to L02 human normal hepatocytes is extremely low; in an in-vivo experiment, in a neutrophile granulocyte reduction mouse Candida albicans infection model, the kidney fungal load reduction effect under each dose of the antibacterial peptide is better than that of anidulafungin and a control peptide. The antibacterial peptide has efficient anti-candida activity, low cytotoxicity and excellent in-vivo curative effect, provides a safe and effective candidate drug for treatment of drug-resistant candidiasis, and has good clinical transformation value.

Several embodiments of the methods and compositions disclosed herein relate to immune cells in which the expression of one or more genes or proteins is modulated (e.g., knocked down or knocked out). In several embodiments, the immune cells are also engineered to express chimeric receptors (e.g., chimeric antigen receptors). In several embodiments, the immune cells having modulated gene expression exhibit enhanced expansion, cytotoxicity against target cells, and / or persistence after administration to a subject, or reduced potential side effects when, for example, the cells are administered to a subject.

The present invention provides affinity matured recombinant monoclonal antibodies (mAbs) and fragments that bind specifically to an HLA-E- peptide complex, including HLA-E-VL9 complexes, and regulate the cytotoxicity effector cell function of NK. Herein, monoclonal antibodies were recombinantly derived from isolated functional HLA-E-VL9-specific mAbs from the naïve human B cell repertoire. Such antibodies are capable of regulating effector cell cytotoxicity and can preferentially recognize HLA-E-VL9 peptide complexes expressed on the surface of tumor cells. The monoclonal antibodies were subject to one or more rounds of affinity maturation. The invention provides methods for using affinity matured HLA-E-VL9 mAbs to modulate NK cell function as part of immunotherapeutic strategies.

The invention discloses application of gamma-aminobutyric acid in preparation of a synergist of an immune checkpoint inhibitor, and belongs to the technical field of tumor treatment. Compared with independent treatment, combined administration of the GABA and the immune checkpoint inhibitor can significantly inhibit tumor growth, increase the infiltration proportion of CD8 + T cells in tumor tissues, and increase the proportions of IFN-gamma +, TNF-alpha + and Perforin + CD8 + T cells, so that the cytotoxic function of the T cells is enhanced. The results show that the GABA can promote the anti-tumor immune response of an organism by adjusting immune cell composition and T cell functions in a tumor microenvironment, so that the treatment effect of the immune checkpoint inhibitor is improved, and a new theoretical basis and application prospect are provided for the GABA as an auxiliary strategy for improving the tumor immunotherapy curative effect.

The present application relates to a kind of evodia rutaecarpine analog and its preparation method and application, belong to the field of synthetic chemistry of medicine. With 4 (3H) -quinazolinone derivative as substrate, phthalocyanine iron as catalyst, evodia rutaecarpine analog is synthesized by intramolecular hydrogen transfer reaction, high yield, low production cost. When concentration is 25 μM, LPS concentration 1 μg / mL, compound 1c, 1t, 1u, 1v inhibit NO release ability is superior to anti-inflammatory drug indometacin, and 1a, 1b, 1i is equivalent to indometacin;Inhibit NO release ability stronger compound 1c, 1t, 1u and 1v are weak to RAW264.7 cell cytotoxicity;Anti-inflammatory effect is obvious, and toxicity is very small, has very high medical value and broad market prospect.

This invention relates to a culture medium for enhancing CAR-T cell performance, the medium comprising tuftin or a derivative thereof. Using this culture medium can improve the memory cell phenotype, enhance the cytotoxicity and killing ability of CAR-T cells against cancer cells, thereby improving the efficacy of CAR-T therapy in the treatment of solid tumors.

The invention provides a low-serum transition multiplication culture method and a culture medium for CD16 high-expression V [gamma] 9V [delta] 2T cells, and belongs to the technical field of cell culture.The culture method comprises the steps that the serum concentration of a culture environment is firstly gradually reduced, induction of interleukin-15 and regulation and control of an antioxidant are combined, then the V [gamma] 9V [delta] 2T cells are massively amplified through a low-serum culture environment, and a large amount of CD16 is expressed; the low-serum culture environment is a culture environment with the serum content equal to or lower than 2%, and by combining low-serum transition, IL-15 induction of CD16 expression, antioxidant reduction of ROS and efficient amplification, high-proportion CD16 + phenotypes are maintained in the amplification process, and the ROS level in cells is reduced. The compound can be used for immune cell therapy and immune cell combined therapy related to antibody dependent cytotoxic action (ADCC), and has potential of function optimization and clinical application.

Co-signaling immunotherapy, via immune checkpoint inhibitors (ICIs), such as ipilimumab (anti-CTLA-4) or nivolumab (anti-PD-1), has revolutionized cancer treatment. However, reinvigorating tumor-infiltrating T cell cytotoxicity has revealed cardiac toxicity in a subset of patients. The inventors found lower transcriptomic expression of CTLA-4 in eccentric hypertrophic cardiomyopathy model, associated with higher cardiac total IgG amount and less B cell infiltration, compared to concentric hypertrophic cardiomyopathy. The present invention relates to a method of treating dilated cardiomyopathy (DCM) in a subject in need thereof comprising a step of administering to said subject a therapeutically effective amount of a cytotoxic T-lymphocyte-associated protein (CTLA-4) molecule.

Several embodiments of the methods and compositions disclosed herein relate to immune cells in which the expression of one or more genes or proteins is modulated (e.g., knocked down or knocked out). In several embodiments, the immune cells are also engineered to express chimeric receptors (e.g., chimeric antigen receptors). In several embodiments, the immune cells having modulated gene expression exhibit enhanced expansion, cytotoxicity against target cells, and / or persistence after administration to a subject, or reduced potential side effects when, for example, the cells are administered to a subject.