71 results about "Phagocytic Cell" patented technology

The invention discloses a ganoderma lucidum fermentation liquid capable of improving the content of total triterpenes and immunity and a preparation method and application thereof, the preparation method comprises the following steps: heating a ganoderma lucidum liquid, and carrying out hot water extraction to obtain a ganoderma lucidum extracting liquid; heating the lucid ganoderma extracting solution to be boiled, after sterilization is finished, after the lucid ganoderma liquid is cooled, adding lactic acid bacteria powder in a specific proportion for fermentation to obtain lucid ganoderma fermentation liquid; and carrying out solid-liquid separation on the fermentation liquor to obtain fermentation supernate, and sterilizing the ganoderma lucidum fermentation liquor to obtain the sterilized ganoderma lucidum fermentation liquor. According to the preparation method disclosed by the invention, the content of total triterpenes in the ganoderma lucidum fermentation liquor is increased, the immunomodulatory activity of the ganoderma lucidum product can be enhanced, and the ganoderma lucidum product has relatively high effects of resisting oxidation, improving the activity of phagocytes, improving the activity of acid phosphatase, improving the immunity and the like, and has a wide application prospect and market potential.

The invention discloses a lipopolysaccharide response type nano antibacterial peptide as well as a preparation method and application thereof, and belongs to the technical field of biology, and the amino acid sequence of the antibacterial peptide is as shown in SEQ ID No.1. Meanwhile, the invention further discloses application of the antibacterial peptide in preparation of drugs for treating gram-negative bacterium infectious diseases. The antibacterial peptide disclosed by the invention can be combined with lipopolysaccharide in a targeted manner to form nanofibers for capturing, and then the nanofibers are clustered and presented to phagocytes for phagocytosis, so that killing of beneficial bacteria in a host is fully avoided. In conclusion, the antibacterial peptide disclosed by the invention can target gram-negative bacteria to rupture membranes and sterilize, fully avoid mistakenly killing beneficial bacteria in a host body and effectively reduce the generation of drug resistance, so that the antibacterial peptide is a nano capture peptide with an immune regulation function, which has great development potential and relatively high application value.

The invention provides universally acceptable “off-the-shelf” hypoimmunogenic pluripotent cells and differentiated cardiac, endothelial, neuronal, islet, or retinal pigment cells thereof. Such hypoimmune cells are used to treat patients in need thereof. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis.

The invention discloses siRNA (small interfering Ribonucleic Acid) nanoparticles capable of efficiently targeting mononuclear phagocytes and mediated by intercellular effect of neutrophils as well as a preparation method and application of the siRNA nanoparticles. The siRNA nanoparticles comprise mesoporous silica nanoparticles carrying siRNA, and functional cell membranes over-expressing ICAM-1 ligands are wrapped outside the mesoporous silica nanoparticles carrying siRNA. Key sentinel cells (mononuclear phagocytes, MPs) for targeted mitochondrial DNA release to treat inflammatory responses caused by mtDNA. The efficient delivery of MPs is realized by using a functionalized cell membrane of an overexpressed ICAM-1 ligand to wrap nano-particles and by virtue of infiltration and rapid apoptosis of a large number of neutrophils in an inflammatory microenvironment and a process (cell burial effect) of specific phagocytosis of the neutrophils by the MPs. Compared with a traditional targeting scheme, the in-vitro targeting efficiency and the in-vivo targeting efficiency of the FCM-coated siNPs scheme are improved by 360% and 120% respectively. The siRNA is guided to target MPs, and the expression of STING is inhibited, so that the inflammatory reaction caused by mtDNA release is regulated and controlled, and an excellent anti-inflammatory curative effect is shown in an inflammatory model mouse.

The invention provides a GAS6 fusion protein as well as a preparation method and application thereof. The provided fusion protein comprises scFv capable of specifically recognizing tumor cell antigens, tumor cells are disguised as apoptotic cells, and phagocytes phagocytize the tumor cells through interaction with TAMRTK. The provided GAS6 fusion protein can be suitable for phagocytosis of various tumor cells and has strong broad spectrum.

Provided herein is a nucleic acid detection system comprising a detection CRISPR system having an effector protein and one or more guide RNAs each designed to bind to corresponding target molecules that are diagnostic for a tick-borne disease state; and an RNA-based masking construct. In some embodiments, the detection system of may comprise i) two or more CRISPR systems, each CRISPR system comprising an effector protein and a guide RNA designed to bind to a corresponding target molecule that is diagnostic for a tick-borne disease state; and ii) a set of detection constructs, each detection construct comprising a cutting motif sequence that is preferentially cut by one of the activated CRISPR effector proteins. Exemplary tick-borne detectable microbes include Babesia microti, Anaplasma phagocytophilum, and Borrelia miyamotoi.

To provide a high affinity SIRP-α D1 domain or variant thereof that binds CD47 with higher affinity than wild-type SIRP-α (signal-regulatory protein α), which is useful to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof.SOLUTION: The present invention provides a polypeptide, comprising: a SIRP-α D1 variant comprising a SIRP-α D1 domain, or a fragment thereof, having an amino acid mutation at residue 80 relative to a wild-type SIRP-α D1 domain; and at least one additional amino acid mutation relative to a wild-type SIRP-α D1 domain at a residue selected from the group consisting of: residue 6, residue 27, residue 31, residue 47, residue 53, residue 54, residue 56, residue 66, and residue 92.SELECTED DRAWING: Figure 3

Provided herein are novel chimeric polypeptides that bind to antigen peptides (e.g., viral antigens or tumor associated antigens) and activate the endogenous phagocytosis signaling pathway. Also provided are compositions and methods for producing such chimeric polypeptides, nucleic acids encoding such chimeric polypeptides, phagocytes that have been modified to express such chimeric polypeptides, and methods for treating various conditions, such as viral infections or cancer.

The invention is directed to cocktails of different antibodies and methods of treating a patient. Antibodies of the collection are specifically reactive to different viral serotypes or species. Cocktails may comprise monoclonal antibodies with one or more having an extended half-life. For treating or preventing viral infections, cocktails may comprise antibodies against conserved regions of HA, NA and M proteins of influenza virus and / or conserved regions of S, M, E, P, N or NS proteins of coronavirus. Monoclonal antibody combinations enhance phagocytosis and killing of viruses by phagocytic cells, and enhance clearance of the infecting virus from the blood.

The invention discloses a coupling molecule with an effect of promoting macrophages to selectively swallow extracellular goods as well as a preparation method and application of the coupling molecule, and belongs to the technical field of biological medicines. The coupling molecule disclosed by the invention is a double-targeting polypeptide and consists of a macrophage targeting peptide fragment, a linker and a target cell targeting peptide fragment, wherein the target cell targeting peptide fragment comprises peptide fragments targeting tumor cells and apoptotic cells. One end of the dual-targeting polypeptide is connected with macrophages, the other end of the dual-targeting polypeptide is connected with tumor cells / apoptotic cells, and the interaction between the macrophages and the tumor cells / apoptotic cells is improved in a molecular glue mode. Aiming at tumor cells, the dual-targeting polypeptide can enhance the phagocytosis and killing effects of macrophages on the tumor cells under the action of a CD47 antibody, so that the anti-tumor effect is achieved; aiming at apoptotic cells, the dual-targeting polypeptide can promote the interplant effect of macrophages, so that the anti-inflammatory effect is achieved. Therefore, the dual-targeting polypeptide disclosed by the invention has relatively good drug development potential.

The present invention discloses an application of an immunomodulatory peptide in the preparation of a drug for preventing and treating bacterial infection, and belongs to the field of biomedical technology; the rice-derived immunomodulatory peptide RDP3 can inhibit bacterial infection in mice, and can alleviate the inflammatory damage of the lung tissue of infected mice and reduce the level of inflammatory factor protein in the serum of infected mice to a certain extent, and can also improve the survival rate of sepsis model mice. RDP3 exerts an antibacterial effect by recruiting phagocytes to the infected site. In view of the unique antibacterial mechanism of RDP3, it can provide a basis for the research and development of RDP3 as a polypeptide anti-infective drug, and provide candidate molecules for the research and development of peptide antibiotics.

The invention discloses polygonatum cyrtonema polysaccharide lipidosome with an immunoregulation effect as well as a preparation method and application of the polygonatum cyrtonema polysaccharide lipidosome. The polygonatum cyrtonema polysaccharide lipidosome is mainly prepared from polygonatum cyrtonema polysaccharide, soybean lecithin and cholesterol. The polygonatum cyrtonema polysaccharide lipidosome with the immunoregulation function is good in stability, capable of slowly releasing polygonatum cyrtonema polysaccharide and easy to prepare in an enlarged mode. Experiments prove that the polygonatum cyrtonema polysaccharide lipidosome can promote proliferation of phagocytes of mice and increase spleen and thymus indexes of immunosuppressive mice, and has an immunoregulation effect.

Provided are a GAS6 fusion protein, a preparation method therefor and the use thereof. The provided fusion protein contains an scFv capable of specifically recognizing tumor cell antigens, and can disguise tumor cells as apoptotic cells and enable phagocytosis of tumor cells by phagocytes by means of interaction with TAM RTK. The provided GAS6 fusion protein is applicable for phagocytosis of various tumor cells, showing strong broad-spectrum properties.

The present invention discloses a CXCL-BPI fusion protein that can be used for treating Gram-negative bacterial infections, a coding nucleic acid thereof, a method for expressing and preparing the same, and a use thereof in the manufacture of a pharmaceutical composition for treating Gram-negative bacterial infections. The CXCL-BPI fusion protein comprises a human ELR+CXC chemokine and a bioactive fragment of N-terminal domain of human BPI, and has the dual functions of both ELR+CXC chemokine and BPI, with ability of binding to LPS and directly killing Gram-negative bacteria, and also inducing chemotaxis and promoting phagocytes to target, bind to and phagocytize Gram-negative bacteria. The mechanism of action of the fusion protein can overcome Gram-negative bacterial drug resistance.

Compositions and methods for preparing and using engineered phagocytes expressing chimeric antigen receptors with enhanced phagocytic activity are described, and the compositions and methods may be suitable for immunotherapy in cancer or infection.

The present invention belongs to the technical field of yolk antibody preparation, and specifically relates to an IBD yolk antibody microsphere and a preparation method thereof. The method uses polygonatum polysaccharide, IBD yolk antibody and bupleurum essential oil as the inner phase of the microsphere, and polylactic-co-glycolic acid copolymer as the outer phase. The special structure of the microspheres prepared by the present invention is conducive to presenting yolk antibodies and polygonatum polysaccharide to immune-competent cells. Phagocytic cells engulf the microspheres and can destroy the shell structure of the microspheres, releasing yolk antibodies and polygonatum polysaccharide, neutralizing the IBD virus infected by the body, playing a preventive and protective role for chickens not infected with IBD, and quickly controlling the condition of chickens infected with IBD.

Methods are provided for treating a subject with for an intracellular pathogen infection, by administering an agent that reduces the binding of CD47 on a infected cell to SIRPα on a host phagocytic cell, in an effective dose for increasing the phagocytosis of infected cells.

The application discloses a CXCL-BPI fusion protein which can be used for treating gram-negative bacterial infection, a coding nucleic acid of the CXCL-BPI fusion protein, an expression preparation method, and application of the CXCL-BPI fusion protein to preparation of a pharmaceutical composition for treating gram-negative bacterial infection. The CXCL-BPI fusion protein comprises a human ELR+CXC chemokine and a human BPI N-terminal domain functional fragment, has the functions of combining LPS, directly killing gram-negative bacteria and chemotactic cell migration, and also has the functions of promoting phagocytes to be guided to combine and phagocytize gram-negative bacteria, and the action mechanism can overcome gram-negative bacterial drug resistance.

The invention provides human phagocytic cells which are not tumorigenic, yet still capable of cell division ex-vivo, such as in cell culture. A culture containing these cells can be expanded manyfold, that is the cell number in such a culture can be increased by a factor of 10 or more. The cells show characteristics of functional phagocytes in a differentiated state and are capable to alleviate pathological defects in in vivo models.

An engineered cell and a use, belonging to the technical field of fine chemical engineering. A photosensitive compound is loaded into a phagocyte, a bacterium in a host is captured by utilizing the innate immunity of the cell, and thus by means of light treatment, the bacterium is killed. Compared with the limitation that a conventional photosensitizer cannot target a living bacterium, the cell formulation can precisely capture a bacterium by means of a macrophage and precisely "deliver" a photosensitive dye to the surface of the bacterium. Therefore, the light treatment can directly act on the surface of the bacterium without damaging an autologous tissue in a patient and has high sterilization efficiency and good treatment safety.

The invention relates to methods of evaluating phagocytosis at a single-cell level by placing one or more phagocytes and one or more particles on a surface and visualizing the phagocytosis of the particles by the phagocytes. The invention also relates to systems for evaluating phagocytosis of a particle by a phagocyte at a single-cell level.

The present disclosure provides a method for judging the level of immune rejection between heterologous cells, tissues or organs, and relates to the field of biological medicine. The method provided by the present disclosure can quickly and objectively compare the interspecies relative phagocytosis rate of phagocytes in a single experiment, and provides a new way for evaluating and researching the level of immune rejection between heterologous cells, tissues or organs.

The invention relates to the technical field of medicine component extraction, and discloses a medicine for resisting hashimoto thyroiditis disease, the medicine comprises an active component and an auxiliary material, the active component is an andrographis paniculata general flavone extract, andrographis paniculata general flavone is used as a main component, and the andrographis paniculata general flavone can reduce exudation of capillary walls, so that the medicine can be used for preventing and treating the hashimoto thyroiditis disease. The andrographis paniculata total flavone extract has an anti-inflammatory effect, is especially effective for symptoms such as upper respiratory tract and diarrhea caused by bacteria and viruses, shows strong antibacterial and antiviral capabilities, can inhibit ADP-induced human platelet aggregation, shortens the dissolution time of euglobulin, and has a good anti-inflammatory effect. The andrographis paniculata extract has a certain protective effect on myocardial injury caused by isoprenaline and experimental myocardial infarction ischemic injury, and the andrographis paniculata extract can enhance the function of phagocytes and improve the staphylococcus aureus phagocytosis capacity of peripheral blood leukocytes, and is used for enhancing immunity and overcoming immunity diseases.

A method for estimating a number of phagocytes in a body fluid of an animal includes stimulating NADPH oxidase activity of the phagocytes; and quantifying a resulting reductive dioxygenation of a chemiluminigenic substrate by an emitted chemiluminescence of the chemiluminigenic substrate using an instrument capable of measuring light. The NADPH oxidase activity of the phagocytes is preferably stimulated by an immunologic or chemical capable of activating a respiratory burst by the phagocytes. The NADPH oxidase activity of the phagocytes is preferably stimulated by a stimulus in solution or coated to a surface contacted by the phagocytes. The stimulus is preferably phorbol myristate acetate (PMA). The animal is preferably human, and the body fluid is preferably blood and / or spinal fluid. The phagocytes are preferably neutrophil leukocytes, and the chemiluminigenic substrate is preferably lucigenin (N,N′-dimethyl-9,9′-biacridinium dinitrate). Also provided is a method of treatment based on the estimation method.

The present disclosure relates to antibodies, multispecific (e.g., bispecific) binding molecules that bind to human Dectin-1, and related methods of use and production. Disclosed herein is a method of targeted phagocytosis for removing disease-causing agents, including host cells / host cell products, microorganisms, or products thereof, by administering a multispecific (e.g., bispecific) binding molecule that comprises a Dectin-1 binding arm and a second arm that specifically binds to the agent. The multispecific (e.g., bispecific) binding molecule allows phagocytes to engage with the target agent and form a synapse between them, promoting the clustering of Dectin-1 on the phagocyte. This stimulates phagocytosis of the target agent and also stimulates cytokine secretion by the phagocyte via the Dectin-1 / Syk / NfkB pathway.

Following DNA damage events, such as radiation therapy, cytosolic dsDNA species are generated that trigger intrinsic STimulator of Interferon Genes (STING) signaling and render cells competent for phagocytic activation contingent on the chemokine CCL5 (C-C Motif Ligand 5). Loss of STING signaling or inducible CCL5, rendered DNA-damaged cells incapable of APC stimulation following phagocytosis. STING signaling facilitated the generation of immunogenic endosomal vesicles comprising the autophagy related proteins RAB9 and LC3, and cytosolic DNA which triggered APC activation in trans, an event which also required extrinsic cGAS / STING-dependent signaling. Further, the combination of radiation treatment in the presence of type I IFN greatly reduced tumor growth while rescuing the ability to generate CTL activity. Reconstitution of STING signaling and / or the combination of radiation treatment in the presence of type I IFN could significantly augment cancer therapy.

The present invention discloses a lipopolysaccharide-responsive nano antimicrobial peptide and its preparation method and application, which belongs to the field of biotechnology. The amino acid sequence of the antimicrobial peptide is as shown in SEQ ID No. 1. Also disclosed is the application of the antimicrobial peptide of the present invention in the preparation of a drug for treating diseases caused by Gram-negative bacteria infections. The antimicrobial peptide of the present invention can target and bind to lipopolysaccharide to form nanofibers for capture, and then present them in agglomerates to phagocytic cells for phagocytosis, fully avoiding the killing of beneficial bacteria in the host. In summary, the antimicrobial peptide of the present invention can target Gram-negative bacteria to break the membrane and kill bacteria, fully avoiding the accidental killing of beneficial bacteria in the host, and effectively reducing the generation of drug resistance. Therefore, it is a nano-capture peptide with immune regulation function that has great development potential and high application value.

There is provided a method for increasing antibody dependent cell phagocytosis (ADCP) activity of a phagocyte in a sample, the method comprising culturing the phagocyte in a low percentage (%) CO2 atmosphere for a period of time sufficient to increase ADCP activity of the phagocyte. In some embodiments, phagocytes are cultured in the presence of target cells. Also provided is a method for determining ADCP activity of phagocytes in a sample, the method comprising: culturing the phagocytes in a low percentage (%) CO2 atmosphere for a period of time sufficient to increase ADCP activity of the phagocytes; and detecting ADCP activity of the phagocytes in the sample. In some embodiments, phagocytes are cultured in the presence of target cells.

The present invention provides attenuated immunostimulatory bacteria whose genome is modified to, for example, reduce toxicity and increase anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, increasing resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T cell function. The increase in phagocyte colonization improves delivery of encoded therapeutic products to the tumor microenvironment and into the tumor, and allows for routes of immunostimulatory bacteria administration such as systemic administration.

Functionalized nanoparticles for inhibiting or preventing pathogen infections (e.g., viral or bacterial infections, such as coronavirus infections) are described. The nanoparticles comprise a biodegradable polymer core and a lipid coating layer that is functionalized with a pathogen-binding receptor (e.g., an angiotensin-converting enzyme 2 (ACE2) receptor protein) and / or a pathogen-binding antibody or an antigen-binding fragment thereof (e.g., a virus-binding antibody or an antigen-binding fragment thereof). The nanoparticles are further functionalized by a phagocyte-specific ligand, e.g., a phosphatidylserine-containing lipid included in the lipid coating layer, to promote clearance of nanoparticle-bound pathogen. Methods of using the nanoparticles to treat or prevent pathogen infections (e.g., coronavirus infections) are also described.