2036 results about "Macrophage cell" patented technology

This invention is directed to the field of medical implants, and more specifically to biodegradable injectable implants and their methods of manufacture and use. The injectable implants disclosed herein comprise glycolic acid and bio-compatible / bio-absorbable polymeric particles containing a polymer of lactic acid. The particles are small enough to be injected through a needle but large enough to avoid engulfment by macrophages. The injectables of this invention may be in a pre-activated solid form or an activated form (e.g., injectable suspension or emulsion).

A method and system for treating a patient to repair damaged tissue which includes exposing a selected area of bone marrow of a patient to ultrasound waves or ultra shock waves so that cells comprising stem cells, progenitor cells or macrophages are generated in the area of the bone marrow of the patient due to the ultrasound, converting the cells from the bone marrow of the patient and reducing the damaged tissue in the bone marrow of the patient by repairing the damaged tissue.

The present invention provides methods and compositions for the production of hematopoietic progenitor cells or endothelial progenitor cells from human pluripotent stem cells using a defined cell culture medium without the need to utilize feeder cells or serum. In some embodiments, differentiation is accomplished using hypoxic atmospheric conditions. The defined medium of the present invention may contain growth factors and a matrix component. The hematopoietic progenitor cells may be further differentiated into cell lineages including red blood cells, macrophages, granulocytes, and megakaryocytes. The endothelial progenitor cells may be further differentiated into endothelial cells. Also disclosed are screening assays for identification of candidate substances that affect differentiation of pluripotent stem cells into progenitor cells.

The present invention is based on the discovery that proteins produced in insect cell cultures are glycosylated in a unique manner that causes them to be selectively imported by cells that express mannose receptors on their membranes, particularly macrophages. Proteins that are selectively imported into cells containing mannose receptors are provided, as well as pharmaceutical compositions containing such proteins and methods for producing such proteins. Application of the present invention to produce proteins useful for treating lysosomal storage disorders is also disclosed. Engineering of cells to express mannose receptors so that they will selectively import proteins produced in insect cells is also taught, as well as a protein targeting system using such cells and proteins. Finally, an improved elution buffer for the purification of proteins produced in insect cells from a Concanavalin A column is provided.

Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.

An objective of the present invention is to provide a therapeutic agent for treating rheumatoid arthritis, juvenile rheumatoid arthritis, macrophage activation syndrome, septicemia, and FR-β expressing leukemia, which induces apoptosis in activated macrophages and folate receptor beta (FR-β) expressing leukemia cells to specifically destroy these cells. An FR-β monoclonal antibody of the present invention is preferably an IgG-type monoclonal antibody which specifically reacts with a human-type FR-β antigen and is produced from a clone resulting from immunization with an FR-β expressing B300-19 cell. The FR-β monoclonal antibody of the present invention specifically reacts with the FR-β antigen of activated macrophages and FR-β expressing leukemia cells and a therapeutic agent of the present invention contains an FR-β antibody immunotoxin which causes apoptosis in activated macrophages and FR-β expressing leukemia cells, as an active ingredient. Further, suitable administration form for the therapeutic agent of the present invention includes intravenous injection as well as joint injection in the case of therapeutic agents for rheumatoid arthritis and juvenile arthritis.

Granulocyte-macrophage colony stimulating factor ("GM-CSF") has been found to act as an adjuvant when administered to subjects. Compositions of GM-CSF and immunogenic compositions are presented, as is the use of GM-CSF alone and in these compositions.

An apparatus and method according to the present invention can be provided, e.g., for a cell specific laser therapy of atherosclerotic plaques, particularly to systems and methods for targeting endogenous light absorbers present within plaque macrophages and exogenous nanoparticle targeting. In one exemplary embodiment, an electro-magnetic radiation can be forwarded to an anatomical structure. The electromagnetic radiation may have at least one property configured to (a) modify at least one characteristic of at least one first cell, and (b) minimize any modification of and / or modify at least one characteristic of at least second cell. The first and second cells may be different from one another, the characteristics of the first and second cells can be different from one another, and the first cell and / or the second cell may have at least one macrophage feature, and the characteristic of the at least one first cell and / or the at least one second cell can be temperature. According to still another exemplary embodiment, a location associated with the first cell and the second cell can be determined. For example, the electromagnetic radiation can be forwarded in a vicinity of the location.

Inhibitors of MIF having a naphthyridine backbone are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R, R1, R2, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

A method for administering a therapeutic or diagnostic agent to a subject is described. The method includes providing a suspension of liposomes comprised of one or more of vesicle-forming lipids selected from (i) a vesicle-forming lipid derivatized with a hydrophilic polymer and (ii) a neutral lipopolymer, said liposomes being associated with said therapeutic or diagnostic agent, forming an aerosol of said liposome suspension; and administering the aerosol to the subject by inhalation. The liposome formulation delivers intact liposomal particles to the respiratory tract of said subject to form a depot of therapeutic agent therein with no observable provocation of an immune response, as measured by neutrophil or macrophage cell count in the lung after administration.

The invention relates to a CD47 and PD-L1 targeting bifunctional fusion protein, belongs to the field of biomedicine, and solves the problems that anti-PD-1 / PD-L1 treatment is poor in a low-immunogenicity tumor treatment effect and anti-CD47 treatment is poor in a targeting ability. The fusion protein is composed of a CD47 binding part and a PD-L1 binding part which are linked by a disulfide bond, can block the binding of CD47 and SIRPalpha, can block the binding of PD-L1 and PD-1, can achieve the effects of activating macrophages to phagocytize tumor cells and promoting antigen presentation in natural immunity, can achieve an effect of promoting the activation of tumor specific T cells in acquired immunity, and has lower blood toxicity; and as compared with the single use of anti-PD-L1 or anti-CD47 for treatment, the fusion protein has better antitumor curative effects and blood safety.

This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and / or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.

The invention provides a human antibody that binds human CSF-1R with high affinity. Antibodies of the present invention have significant advantages over the antibodies known in the art by being multifunctional: inhibiting signaling of CSF-1R, internalizing and inducing CSF-1R degradation and stimulating ADCC in cell including tumors, macrophages and monocytes. They are also shown to be effective in treating leukemia, breast, endometrial and prostate cancer alone or in combination with docetaxel, paclitaxel, Herceptin® or doxorubicin.

Detectably labeled macrophage scavenger receptor antagonists useful for the diagnosis and monitoring of various cardiovascular diseases including but not limited to atherosclerosis, vulnerable plaque, coronary artery disease, renal disease, thrombosis, transient ischemia due to clotting, stroke, myocardial infarction, organ transplant, organ failure and hypercholesterolemia.

The invention provides a chimeric antigen receptor (CAR) (a) an antigen binding domain of HN1 or SS, a transmembrane domain, and an intracellular T cell signaling domain, or (b) an antigen binding domain of SS1, a transmembrane domain, an intracellular T cell signaling domain, and a granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor 2 leader. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

This invention provides: agents determined to be capable of specifically inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell, but not a T cell-tropic isolate of HIV-1 to a CD4+ cell; and agents determined to be capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4+ cell, but not a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell. This invention also provides: agents capable of specifically inhibiting the fusion of a macrophage tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1; and agents capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 with a CD4+ cell susceptible to infection by a T cell-tropic isolate of HIV-1. The agents include but are not limited to antibodies. This invention further provides: methods of inhibiting fusion of a macrophage-tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1 which comprises contacting the CD4+ cell with an amount of an agent capable of specifically inhibiting such fusion so as to thereby inhibit such fusion; and methods of inhibiting fusion of a T cell-tropic isolate of HIV-1 with a CD4+ cell susceptible to infection by a T cell-tropic isolate of HIV-1 which comprises contacting the CD4+ cell with an amount of an agent capable of specifically inhibiting such fusion so as to thereby inhibit such fusion.

The present invention relates to a microvesicle that is derived from nucleated mammalian cells, which are smaller than the nucleated cells. The microvesicles of the present invention can be used in the delivery of a therapeutic or diagnostic substance to specific tissues or cells, and more particularly, relates to microvesicles derived from monocytes, macrophages, dendritic cells, stem cells or the like, which can be used to deliver specific therapeutic or diagnostic substances for treating and / or diagnosing tissue associated with cancer, diseased blood vessels, inflammation, or the like.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a plurality of assays, one or more of which is configured to detect a kidney injury marker selected from the group consisting of metalloproteinase inhibitor 2, soluble oxidized low-density lipoprotein receptor 1, interleukin-2, von Willebrand factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor receptor superfamily member 11B, neutrophil elastase, interleukin-1 beta, heart-type fatty acid-binding protein, beta-2-glycoprotein 1, soluble CD40 ligand, coagulation factor VII, C—C motif chemokine 2, IgM, CA 19-9, IL-10, TNF-α, and myoglobin as diagnostic and prognostic biomarkers in renal injuries.

The invention relates to the field of protein, and specifically relates to a milk-derived bioactive polypeptide LPLP with in-vitro antioxidant activity and immunity improving function. An amino acid sequence of the polypeptide is Leu-Pro-Leu-Pro. In-vitro anti-oxidation and in-vitro immune function promotion experiments prove that the polypeptide LPLP has good anti-oxidation bioactivity and cellular immunity promotion activity. With the polypeptide LPLP, free radicals in bodies can be removed, such that harm of the free radicals to human bodies can be reduced; and the bioactive polypeptide LPLP can enhance macrophage phagocytic function, can improve body capacity for resisting external pathogens, can reduce body incidence rate, and does not cause body immunological rejection. The polypeptide has important significance in developing dairy products, health products and medicines with anti-oxidation function and immunity enhancing function.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m / II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

Methods for treating viral infections using polyamine analogs, including mitoguazone (MGBG), are provided. In these methods, polyamine analogs destroy macrophages that act as viral reservoirs, facilitating the destruction of the viruses that dwell within the macrophages. Examples of viral infections that may be treated with the present methods include, but are not limited to, infections from human immunodeficiency viruses. These methods differ from previous methods of treatment using polyamine analogs, wherein the polyamine analogs were administered only as anti-tumor agents.

Disclosed are multi-compartmental nanoparticulate systems for imaging as well as the diagnosis, monitoring, and treatment of inflammation and / or disease. These multicompartmental nanoparticulate systems can be used to target specific cells or ceullular structures. Furthermore, these systems are capable of simultaneous delivery of hydrophilic and lipophilic compositions. Finally, these systems also allow for temporal control of drug delivery.

The invention relates to a method and novel types of agents for modulating appetite and / or body weight in a subject. Moreover, the invention relates to a method of screening for agents which interact and modulate the activity of the receptor complex for macrophage inhibitory cytokine-1 (MIC-1).

The invention discloses rhodococcus ruber and application of same as an immunologic adjuvant in preparing vaccine. The rhodococcus ruber is also called rhodococcus ruber RDC-01, and the preservation number is CGMCC (China General Microbiological Culture Collection Center) NO. 16640. The rhodococcus ruber disclosed by the invention has the function of increasing and regulating the body immunity andis capable of nonspecifically enhancing the activity of TB (Tuberculosis) lymphocyte, macrophagocyte and NK cells and inducing multiple cell factors such as interferon, and the rhodococcus ruber canbe used as the immunologic adjuvant after being inactivated so as to be added in an oil-adjuvant inactive vaccine, so that generation of an animal antibody induced by the vaccine can be obviously promoted; compared with single use of the oil-adjuvant inactive vaccine, a high-titre antibody can be generated, the use is safe, long-term and short-term toxic and side effects are not generated, and anapplication prospect in the field of preparation of vaccines for animals is good.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.