36 results about "CCR2" patented technology

The application discloses a preparation method of CCR2+ gamma delta T cells with anti-tumor activity and migration ability, and belongs to the technical field of cells; the method comprises the following steps: step (1), PBMC of peripheral blood of a healthy person is extracted, inoculated into complete culture medium, and added with zoledronic acid, IL-15 and metformin, and then is cultured in a T25 culture bottle; step (2), complete culture medium is supplemented, the cell concentration is adjusted, and then the cells are transferred into a T75 culture bottle for culture; step (3), complete culture medium is supplemented, the cell concentration is adjusted, glucocorticoid and nicotinamide are added, and then the cells are transferred into a T150 culture bottle for culture; step (4), cells are collected at D6, rinsed with normal saline, resuspended with complete culture medium, the cell concentration is adjusted, and then the cells are inoculated into a T300 culture bottle for culture; and step (5), complete culture medium is supplemented every two days from D8 to D16, the cell concentration is maintained, and then the cells are harvested at D16 to obtain CCR2+ gamma delta T cells.

The invention relates to the technical field of drug carriers, in particular to a mesoporous nanomaterial coupled with a CCR2 antibody and a preparation method and application of the mesoporous nanomaterial. According to the invention, the aminated mesoporous material is used for loading the drug and is coupled with the CCR2 antibody, so that the obtained CCR2 antibody coupled mesoporous nano material can target CCR2 + macrophages, the bioavailability of drugs such as matrine is improved, and the side effect is reduced. According to the invention, leading-edge technical elements such as a mesoporous nano-carrier, CCR2 antibody targeted modification and macrophage precise delivery are introduced, so that a carrier-drug-antibody ternary innovative combination system is formed.

The present disclosure relates to antibodies and antibody fragments specific for CCR2. As reactivity with marmoset CCR2, which is a species that is crucial to further preclinical and clinical development, is lost, almost all attempts to humanize the original antibody are notified as failure. The antibodies are useful in the treatment of inflammatory diseases, autoimmune diseases, hematological malignancies, and potentially other diseases.

The invention relates to pharmaceutical compositions comprising: (a) at least one angiotensin receptor blocker or a pharmaceutically acceptable salt thereof, and (b) at least one chemokine receptor pathway inhibitor or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising: (a) at least one angiotensin receptor blocker or a pharmaceutically acceptable salt thereof; and (b) at least one chemokine receptor pathway inhibitor or a pharmaceutically acceptable salt thereof that inhibits a component of the chemokine receptor pathway other than the chemokine receptor. Sustained-release oral pharmaceutical compositions comprising the pharmaceutical composition are described, as well as sustained-release injectable pharmaceutical compositions comprising the pharmaceutical composition.The invention further relates to tablets, capsules, injectable suspensions, and compositions for pulmonary or nasal administration comprising the pharmaceutical composition. Also described are: methods for evaluating the efficacy of the pharmaceutical composition; methods for evaluating the inhibitory or partial inhibitory activity of the pharmaceutical composition; methods for treating, alleviating, or preventing a condition or disease comprising administering a therapeutically effective amount of the pharmaceutical composition to a subject; and the use of the pharmaceutical composition for manufacturing a pharmaceutical dosage form for the treatment of a disease.

The present invention relates to certain compounds of Formula (I) that function as a proteolysis targeting chimera (PROTAC) against CCR2; wherein X, L, E3, ring A, integer a, Y, ring B, integer b and Z are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which CCR2 activity is implicated.

The application discloses an extracellular vesicle delivery system loaded with interfering nucleic acid, and a preparation method and application thereof. The delivery system comprises extracellular vesicles and interfering nucleic acid loaded in the extracellular vesicles, and the interfering nucleic acid is preferably siRNA targeting inflammation-related genes, and more preferably siCCR2 targeting CCR2 mRNA. The preparation method comprises culturing cells, collecting culture supernatant, obtaining extracellular vesicles through centrifugation and filtration, and loading interfering nucleic acid into the extracellular vesicles through electroporation. Animal experiment results show that the extracellular vesicles loaded with siCCR2 can improve heart function of myocardial infarction model mice, reduce myocardial infarction area, reduce heart weight related indexes and relieve myocardial fibrosis reconstruction; and in-vitro cell safety evaluation results show that the extracellular vesicles have good cell compatibility. The application provides a nucleic acid delivery scheme for inflammation-related injury and tissue reconstruction intervention.

Provided herein are compositions, uses thereof and methods for treating muscular dystrophy and / or chronic inflammatory myopathy. The composition comprises at least one compound inhibiting CCR2 signaling and at least one compound inhibiting CSF-1R signaling.

The application of CCR2 / CCR5 inhibitor in the preparation of drugs for treating immune checkpoint inhibitor associated pneumonia and products belong to the field of biological medicine technology. The technical problem to be solved is the new application of CCR2 / CCR5 inhibitor in the preparation of drugs for treating pneumonia, and the treatment effect of immune checkpoint inhibitor associated pneumonia is better than that of single inhibitor. The technical solution is the application of CCR2 / CCR5 inhibitor in the preparation of drugs for treating pneumonia.

Provided herein are single chain variable fragment antibodies that are directed against N-terminal or extracellular loop regions of CCR2. The scFvs can be used alone or in combination to modify macrophage number and migration and to reduce the growth of tumors.

The present invention relates to a composition which is for preventing or treating bone diseases and includes CCR2 as an active ingredient. It was confirmed that a C—C chemokine receptor type 2 (CCR2) protein, a polynucleotide encoding the CCR2 protein, or a mesenchymal stem cell transduced with the CCR2 according to the present invention neutralize bone disease factor MCP-1, thereby reducing the collagen epitope (CTX-II) and collagen metabolism factors (MMP1 and MMP3) relating to collagen absorption in the body. In addition, it was confirmed that the expression of the SOX9 gene and anti-inflammatory cytokines (TGF-β and IL-10) related to cartilage differentiation was significantly increased. Thus, the present invention has excellent regenerative ability against osteoarthritis and excellent pain suppression and alleviation effects, and thus can be effectively used for preventing or treating bone diseases such as osteoarthritis.

This invention belongs to the field of medicine, specifically disclosing a drug-loaded biomimetic nanodecoy based on genetic engineering, its preparation method, and its application. The drug-loaded biomimetic nanodecoy of this invention comprises CCR2-overexpressing nanovesicles, and the hydrophobic regions of the nanovesicles are loaded with curcumin. This invention also provides a method for preparing the drug-loaded biomimetic nanodecoy based on genetic engineering and its application. The overexpressed CCR2 is used to adsorb excess CCL2 to inhibit the binding of macrophages to CCL2, preventing macrophage chemotaxis and subsequent TGF-β production. This inhibits the activation of hepatic stellate cells by removing pro-fibrotic mediators upstream; simultaneously, curcumin is released to block the downstream TGF-β / Smad signaling pathway, thereby inhibiting the activation of hepatic stellate cells.

The present application belongs to the field of biological medicine, and particularly relates to a multiple small nucleic acid delivery system and a multiple target vaccine. The present application aims to solve the problem that the treatment effect of single target in tumor biological treatment is not ideal. The technical solution for solving the problem is to provide a multiple small nucleic acid delivery system in which a hydrophobic modified polypeptide is loaded with multiple small nucleic acids. The sequence of the polypeptide is VQWRIRVAVIRK, and the hydrophobic modification is coupling of a hydrophobic fragment to the nitrogen terminal end of the polypeptide. Meanwhile, the present application provides a multiple small nucleic acid system containing siRNA molecules of STAT3, CCR2 and TGF-beta and CpG ODNs molecules. The polypeptide of the present application can quickly self-assemble into nanomicelles after being mixed with small nucleic acids to form a nanosystem loaded with multiple small nucleic acids; as an in situ vaccine carrier, the nanosystem can be used for treating different tumors by targeting different targets in the tumor microenvironment; and the nanosystem is low-toxic and safe, has a short preparation cycle, and has a good clinical application prospect.

This invention provides a method for screening peptides that specifically target T cells, comprising providing T cells having a subset selected from CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L) The T cells are labeled with at least one of the following surface antigen markers: CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7. The T cells are then contacted with a peptide display library, and target peptides that specifically bind to the T cells are screened therefrom.

The invention belongs to the technical field of biological medicines, and particularly relates to application of IAA in preparation of a medicine for preventing and treating atherosclerosis. Atherosclerosis is caused by excessive deposition of cholesterol, and IAA can significantly reduce formation of aorta and aortic sinus lipid plaques of atherosclerosis model mice by adjusting monocyte chemotactic and adhesion functions (specifically, down-regulating expression of chemotactic factors CCL2 and CXCL1, receptors CCR1 and CCR2, adhesion molecules ICAM1 and the like). An injection preparation is preferably selected as a medicine dosage form, the intervention dosage of IAA is 50 mg / kg, and the intervention time is 15 weeks. The new application of IAA in prevention and treatment of atherosclerosis is explored for the first time, the action mechanism of IAA is clear, the intervention effect is remarkable, and a new target spot and thought are provided for developing safe and effective medicines and means for preventing and treating atherosclerosis.

The invention discloses a diagnosis and treatment target device for cytophagic lymphocytosis. The device comprises a detection module, a detection module and a control module, wherein the detection module is used for detecting the expression quantity of four genes, namely CCR2, CDKN1A, TNFSF10 and TP53INP2 in a patient sample of a current patient; the detection module is used for detecting the expression quantity of four genes, namely CCR2, CDKN1A, TNFSF10 and TP53INP2; the analysis module is used for carrying out difference analysis on the expression quantity and the expression quantity of a healthy control group to obtain a molecular characteristic spectrum related to the HLH; the diagnosis typing treatment module is used for performing diagnosis typing on the current patient according to a difference mode of the molecular characteristic spectrum and treating according to a diagnosis typing result, so that serious treatment toxicity such as myelosuppression and liver and kidney injury of a traditional chemotherapy regimen can be reduced, the safety and effectiveness of clinical treatment of the patient are improved, and higher specificity and accuracy are achieved; a foundation is laid for developing a novel diagnostic tool, and a direct and feasible candidate scheme and a theoretical basis are provided for developing a high-efficiency and low-toxicity HLH new therapy.

Provided is a method for screening polypeptides that specifically target T cells, comprising: providing T cells having a surface antigen marker selected from at least one of CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L), CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7; and contacting the T cells with a polypeptide display library, and screening therefrom target polypeptides that specifically bind to the T cells.

The present application relates to the technical field of idiopathic pulmonary fibrosis inhibitor, and specifically discloses an idiopathic pulmonary fibrosis inhibitor, and the molecular inhibitor comprises compound HO11553 and / or compound HO11552.The molecular inhibitor of the present application targets G protein-coupled receptor CCR2, and the molecular inhibitor is a dual-pocket inhibitor capable of being combined with the orthosteric binding site and the allosite binding site of CCR2 respectively, the molecular inhibitor slows down the progress of pulmonary fibrosis by inhibiting CCR2, provides an effective means for the treatment of IPF, and has good application prospect.

This invention belongs to the field of biomedical technology and discloses the application of CCR2 inhibitors in the preparation of drugs for treating hemophagocytic lymphohistiocytosis (HLH). By establishing a mouse model of HLH, this invention reveals for the first time that CCR2 can serve as an effective drug target for treating HLH. Experiments showed that treatment with the CCR2-specific antagonist RS102895 significantly reduced splenomegaly, improved peripheral blood cell reduction, alleviated liver damage, corrected metabolic disorders in model mice, and effectively inhibited serum cytokine storm and abnormal activation of splenic macrophages. Based on these findings, CCR2 can serve as a novel target for HLH treatment, and its inhibitors can be used to prepare highly effective and low-toxicity drugs for treating HLH.

The present disclosure is drawn to the combination therapy of a Chemokine Receptor 2 (CCR2) antagonist and a PD-1 and / or PD-L1 inhibitor in the treatment of cancer.

The present disclosure relates to heterobifunctional molecules, referred to as cytotoxicity targeting chimeras (CyTaCs) or antibody recruiting molecules (ARMs) that are able to simultaneously bind a target cell-surface protein as well as an exogenous antibody protein. The present disclosure also relates to agents capable of binding to a receptor on a surface of a pathogenic cell and inducing the depletion of the pathogenic cell in a subject for use in the treatment of cancer, inflammatory diseases, autoimmune diseases, viral infection, or bacterial infection.

This invention relates to a drug for treating ischemia-reperfusion injury and its application. The drug activates the CCL2-chemokine receptor 2 signaling axis, triggering the downstream G protein αi2 subunit-mediated phosphatidylinositol 3-kinase / protein kinase B signaling pathway. This, in turn, synergistically regulates the antioxidant defense system driven by nuclear factor erythroid 2-related factor 2 and the B-cell lymphoma 2-mediated anti-apoptotic pathway, thereby treating the ischemia-reperfusion injury. The results of this study establish a novel therapeutic strategy for testicular ischemia-reperfusion injury based on engineered exosomes, and simultaneously reveal the previously undiscovered cytoprotective role of the CCL2 / CCR2 signaling axis in non-immune cells.

The invention belongs to the technical field of biomedicine, and relates to a preparation method and application of a membrane fusion liposome. A drug-loaded cationic liposome and a CCR2 overexpression macrophage membrane are mixed and extruded, and the macrophage membrane is promoted to be integrated into double layers of the liposome, so that the membrane fusion liposome is obtained. According to the membrane fusion liposome, on one hand, PSMP is eliminated, recruitment of inflammatory macrophages is destroyed, and inflammation is relieved from the outside; on the other hand, the delivered STING inhibitor blocks the STING pathway in the injured renal tubular epithelial cells from the inside, the inflammation level is doubly relieved, and the synergistic anti-inflammatory and kidney protection effects are achieved.

The present application relates to a hybrid cell membrane nano delivery carrier which can target intracranial inflammatory lesions, which is a spherical vesicle coated with a hybrid cell membrane coating, wherein the hybrid cell membrane coating is composed of platelet cell membrane proteins and HEK293t cell membrane proteins overexpressing chemokine receptor CCR2 genes at a weight ratio of 1:2-2:1. The present application also provides a nano drug which can target intracranial inflammatory lesions, which is composed of drug-loaded liposomes coated with the hybrid cell membrane coating. The present application also provides a preparation method of the nano delivery carrier and the nano drug and applications thereof. The nano delivery carrier of the present application simultaneously expresses platelet membrane marker proteins and chemokine receptor CCR2 genes on the surface, and the nano drug formed by loading specific small molecule drugs in the nano delivery carrier can significantly improve the cognitive function of Alzheimer's disease model mice and reduce the deposition of amyloid plaques in the brain.

The invention relates to hepatic fibrosis intervention, and provides a pharmaceutical composition for treating and / or preventing hepatic fibrosis related to TET2 function deficiency type myeloid cells and application of the pharmaceutical composition. The composition comprises: (a) an inhibitor or antagonist for inhibiting chemotactic signals mediated by CCL2 and / or CCL8 and CCR2 and / or CCR3; and (b) an IL-6 pathway inhibitor. Preferably, (a) is Bindarit or a pharmaceutically acceptable salt thereof, and (b) is an IL-6 neutralizing antibody or an IL-6 receptor antibody. According to the composition, by reducing mononuclear cell recruitment / proinflammatory mononuclear cell source macrophage infiltration and blocking IL-6 mediated hepatic stellate cell activation, collagen deposition is relieved, and fibrosis indexes such as alpha-SMA and Col1a1 are reduced. Animal experiments show that in a CCl4-induced myeloid Tet2 deletion mouse model and an old-age chimeric model, combined administration is superior to single administration.

Therapeutic agents and treatment methods for urologic cancers, particularly urologic cancers with reduced lysine (K)-specific demethylase 6A (KDM6A) function, the agents and methods being characterized by suppressing both IL-6 activity and CCR2 / CCL2 activity, are provided.

This invention discloses the application of substances that reduce CCR2 content or activity in the treatment or prevention of fever with thrombocytopenia syndrome (FPS). This invention discovers that CCR2 is a target for the prevention and treatment of FPS virus infection, revealing that CCR2 plays an important role in the infection and proliferation of FPS virus and can serve as a target for inhibiting FPS virus infection. Utilizing CCR2 inhibitors as candidate drugs for the prevention and treatment of FPS virus shows great research potential. This invention provides a theoretical basis for using CCR2 as a target for the treatment of FPS and has significant application value for the treatment of FPS virus infection and the development of drugs for treating FPS virus infection.

The invention discloses a humanized structure-oriented chemokine receptor 2 mutant and application thereof. The humanized structure-oriented chemokine receptor 2 mutant is characterized in that an amino acid sequence is shown as SEQ ID NO. 2. The invention also discloses an application of the humanized structure-oriented chemokine receptor 2 mutant in preparation of drugs for treating cerebral hematoma. According to the humanized, high-activity and low-immunogenicity CCR2 mutant protein provided by the invention, the design is based on a human CCR2 wild type sequence (UniProt login number: P41597-1), a human CCR2 extracellular functional region framework is completely reserved, the introduction of redundant sequences is avoided, and then targeted mutation is carried out aiming at the binding activity, the protein conformation stability and the solubility of CCL2. Cerebral hematoma removal and neurological function repair can be accelerated, and absorption of rat cerebral hematoma is promoted. The cerebral hemorrhage prognosis can be effectively improved.

The present disclosure relates to methods of treating leukemia using a heterobifunctional molecule, referred to as a cytotoxicity targeting chimera (CyTaC) or antibody recruiting molecule (ARM), that is able to simultaneously bind a target cell-surface protein as well as an exogenous antibody protein.