63 results about "Cell cytotoxicity" patented technology

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

Described herein are receptor configurations that allow ligation of multiple targets expressed in cancer cells via two main mechanisms: direct binding via an antibody-derived single chain variable fragment (scFv), and indirect binding through the high-affinity engagement of the Fc component of an antibody. When expressed in human T lymphocytes, these receptors (CARFcR) can trigger powerful CAR-T cell activity as well as antibody- dependent cell cytotoxicity (ADCC), either simultaneously or sequentially. CARFcR T cells are not affected by soluble antibodies, but they can be redirected and activated by antibodies bound to target cells. Therefore, such T cells can be used to redirect adoptive T cell therapy towards another tumor-associated antigen "on the fly" using clinically available antibodies. They also provide a practical way to target multiple antigens simultaneously with a single receptor, a feature that should be useful in cell therapies directed against phenotypically heterogeneous tumors.

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 and / or CD8+ T-cells positive for cell-surface expression of NKG2A (“NKG2A+”). Herein, monoclonal antibodies were recombinant.lv derived from isolated functional HLA-E-VL9-specific mAbs from HLA-E-VL9 peptide-immunized HLA-B transgenic mice and from the naive 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 7 maturation. The invention provides methods for using affinity matured HLA-E-VL9 mAbs to modulate NK and / or CD8+T-cell function as part of immunotherapeutic strategies.

Provided herein are anti-EGFRvIII antibodies and binding fragments thereof. The anti-EGFRvIII antibodies of the present disclosure are useful for the treatment of cancer by, for example, antibody dependent cytotoxicity (ADCC). Also provided herein are methods of making and using anti-EGFRvIII antibodies for the treatment of cancer, as well as polynucleotides encoding the antibodies.

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 contents disclosed herein include methods, compositions, and kits suitable for use in enhanced adoptive T cell therapy. In some embodiments, the methods include contacting an isolated organelle complex with a population of T cells to produce a population of T cells comprising the organelle complex. The organelle complex can include mitochondria and one or more of endoplasmic reticulum, peroxisome, lysosome, and Golgi. The population of T cells exhibits one or more of the following: enhanced expansion capability, enhanced cytotoxicity against a target cell, enhanced resistance to depletion, and enhanced persistence compared to a population of T cells not comprising an exogenous organelle complex.

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.

The invention provides a ceritinib derivative, a preparation method and application thereof and a medicine, and relates to the technical field of pharmacy. According to the invention, a boric acid derivative or a boric acid ester derivative is used for modifying a piperidine region of ceritinib, and a reversible covalent bond is formed by an empty orbit of sp2 of a boron atom and nucleophilic residues in protein, so that cytotoxicity caused by off-target and cytotoxicity to normal cells are reduced; meanwhile, the compound has broad-spectrum cytotoxicity on tumor cells. Experimental data show that when the ceritinib derivative provided by the invention is applied as a medicine, the ceritinib derivative has cytotoxicity to tumor cells such as H228 cells, MCF7 cells, HeLa cells, U251 cells, MDA-MB-231 cells and the like, and has relatively low cytotoxicity to normal LO2 cells of a human body. # imgabs0 #

The present disclosure relates to methods for expanding and increasing the cytotoxic activity of natural killer cells comprising co-culturing, as feeder cells, a population of myeloid leukemia cells engineered to express one or more of membrane-bound IL-21 (mbIL-21) or membrane-bound IL-15 (mbIL-15) in the presence of cytokine support. The present disclosure also relates to a population of acute myeloid leukemia cells engineered to express one or more of membrane-bound IL-21 (mbIL-21) or membrane-bound IL-15 (mbIL-15). The present disclosure also relates to methods of treating cancer employing the step of expanding natural killer cells using feeder cells engineered to express one or more of membrane-bound IL-21 (mbIL-21) or membrane-bound IL-15 (mbIL-15).

Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

The invention relates to an anti-delta-like ligand 3 monoclonal antibody and application thereof, and belongs to the technical field of biology. The invention provides a monoclonal antibody for resisting a delta-like ligand 3 (DLL3), and research shows that the monoclonal antibody has high affinity and high specificity to the delta-like ligand 3, and the monoclonal antibody has high endocytosis efficiency in cells with high expression of the delta-like ligand 3; meanwhile, research shows that an antibody-coupled drug obtained by coupling the monoclonal antibody and an anti-tumor drug through a joint has relatively strong target cell killing activity, and the antibody-coupled drug obtained by coupling the monoclonal antibody and the anti-tumor drug through the joint has relatively good in-vivo anti-tumor activity, which can be seen that the antibody-coupled drug has relatively good anti-tumor activity. The monoclonal antibody can effectively target neuroendocrine tumors, and has great application prospects in preparation of neuroendocrine tumor treatment drugs.

The invention discloses a novel nitrogen mustard derivative and a preparation method thereof. The method comprises: firstly synthesizing an amine raw material by using the hydrochloride of N,N-di(2-chloroethyl)-1,4-phenylenediamine, anhydrous DCM and triethylamine, reacting the amine raw material with triphosgene at room temperature, adding an anhydrous DCM solution of an aniline raw material under ice bath condition after confirming that the N,N-di(2-chloroethyl)-1,4-phenylenediamine is converted into an intermediate by TCL board, reacting at room temperature under nitrogen protection, stopping the reaction after confirming that the intermediate is completely converted by TCL board; adding water to the reaction solution to remove the remaining triethylamine, extracting with anhydrous DCM, collecting and merging organic layers, washing with saturated NaCl, drying with anhydrous Na2SO4, concentrating, purifying on a silica gel column, and recrystallizing to obtain the novel nitrogen mustard derivative. The present invention uses nitrogen mustard as the parent structure to design and synthesize 5 new nitrogen mustard derivatives 5c-5e, 5g-5h, which show broad-spectrum anti-tumor proliferation effects on CCRF-CEM, K562 and HL-60 cells, and have relatively low cytotoxicity to normal human liver cells L02.

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 invention provides a method for preparing CD7-CAR-T cells and their application. Specifically, the present invention provides a method for preparing CD7-CAR-T cells, adjusting the transfection sequence and transfection time of a lentivirus expressing a CD7 blocking molecule and a lentivirus expressing a CD7-CAR, thereby improving the transfection efficiency and enhancing the cytotoxicity of CAR-T cells. The present invention also provides CD7-CAR-T cells prepared by the method and their application.

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;

A synthetic cytokine signaling system includes an engineered cytokine signaling chain encoding a transmembrane polypeptide that contains a particular variant intracellular domain of IL9R and an extracellular domain of a cytokine receptor such as IL2Rβ, IL4Rα, IL7Rα, IL9R, and IL21R. Depending on whether a functionally compatible cytokine ligand domain is fused on the N-terminus, the engineered cytokine signaling chain may be in a self-activating form, or optionally may be in a non-self-activating form. In the latter case, the synthetic cytokine signaling system may further include an engineered cytokine ligand chain encoding a corresponding cytokine ligand that can be membrane-bound or secreted. Immune cells modified with the synthetic cytokine signaling system displays improved characteristics compared with unmodified immune cells, such as the zero or reduced dependency on IL-2 when cultured in vitro, enhanced activation upon antigen stimulation, increased cytotoxicity against target cells, and improved tumor control capacity when transferred in vivo.

The present invention discloses a new use of androsterone-4,6,8(9),13(14)-tetraene-3,11,16-trione, namely, its use in preparing a drug for treating acute lymphocytic leukemia. The present invention adopts an acute lymphocytic leukemia cell line (T line, B line) and detects the IC value of androsterone-4,6,8(9),13(14)-tetraene-3,11,16-trione in an ALL cell line by a CCK-8 method. 50 The present invention studies the cytotoxicity of androst-4,6,8(9),13(14)-tetraene-3,11,16-trione to human umbilical vein fusion cells Eahy.926 and rat normal liver cells BRL-3A. Flow cytometry technology shows that the compound mainly inhibits the growth of leukemia cells by inducing apoptosis and blocking the cell cycle. The present invention not only increases the diversity of the biological activity of androst-4,6,8(9),13(14)-tetraene-3,11,16-trione, but also provides a new direction for the research and development of new drugs for the treatment of leukemia.

Described herein are multicistronic expression systems that encode chimeric proteins, specifically membrane-cleavable chimeric systems and chimeric antigen receptors for administration in combination with the cytokine IL2 for treating a subject having cancer. Also described herein are nucleic acids, cells, and methods directed to the same.

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 invention relates to the technical field of drug screening, in particular to a compound for enhancing the NK cytotoxic activity function and a use method. The inventor finds that the Astilbin screened by the invention is contacted with the NK cells, so that the cytotoxicity of the NK cells is greatly improved, amplification markers of the NK cells are also improved to a certain extent, phenotypes of the NK are not influenced, and the functions of the NK cells are improved. Moreover, the inventor also finds that after the NK cells are treated by the Astilbin, not only can the NK cells from iPSC be improved, but also the NK cells from cord blood have similar results. It is shown that the function of improving the cell function can be achieved on the NK from various sources through pretreatment of the Astilbin.

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.

Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

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.

The present disclosure is directed to tetrahydroquinazoline derivatives of Formula (I) and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV naïve cells, and for the treatment or prophylaxis of infection by HIV, or for the treatment, prophylaxis or delay in the onset or progression of AIDS or AIDS Related Complex (ARC).