38 results about "CX3CR1" patented technology

The present invention provides compositions and methods for diagnosing and treating diabetes and insulin resistance. In particular, the invention provides methods of identifying modulators of CX3CR1 and using those modulators to treat diabetes, as well as methods of diagnosing diabetes by measuring the levels of CX3CR1 or fractalkine in a patient.

The invention relates to the field of medical diagnostics. More specifically, the invention relates to methods to diagnose or screen for inflammatory conditions or disease, including auto-inflammatory disease and affective disorder, in a subject, preferably a human subject, by assaying for a marker for an inflammatory disease. Provided is a method to diagnose, screen for or predict the development of an affective disorder (AD), preferably bipolar disorder (BP), in a subject, the method comprising determining the level of at least one, preferably at least two, more preferably at least three, most preferred at least four, AD-specific gene product(s) in a biological sample isolated from the subject, preferably peripheral blood monocytes, wherein the gene is selected from the group comprising ATF3, phosphodiesterase 4 B, CXCL2, BCL2-related protein A2, Dual specificity phosphatase 2, TNFα-induced protein 3 / A20, BTEB1 CXCL3, Chemokine CCL-3 like, CCL-4, CCL20, CX2CR1, Amphiregulin, Thrombomodulin, Heparin-binding EGF-like growth factor, DNA-damaged inducible transcript, V28 chemokine-like receptor, TRAIL. MAPK6, B4BP4, PBEF1, Thrombospondin 1, MAFF, HSP70, CCL2, MCP-3, CCR2, CX3CR1, DOK1, HBB, G-gamma globin, THBD, PHLDA1, DTR and GNLY.

There are provided uses of an antibody directed to CX3CR1 and fractalkine. Killer lymphocytes can be readily identified, eliminated and separated by using an anti-CX3CR1 antibody. Further, there can be provided an antibody drug for suppressing chemotaxis and cytotoxic activity of killer lymphocytes by suppressing an interaction between CX3CR1 and fractalkine.

The invention discloses a TLR4 (Toll-like receptor) compound of targeting microglia as well as a preparation method and application of the compound in the pharmaceutical field, and belongs to the field of biomedicine. The compound is formed by binding fusion peptide of Q9 peptide (QQQKKKKKK) and T9 peptide (LTQQVVMKF) and TLR4RNAi through an electrostatic interaction; through a guiding function of the Q9 peptide, the compound can specifically target a specific CX3CR1 receptor on the surface of the microglia; when the T9 peptide acts with the CX3CR1 receptor, the TLR4RNAi is efficiently transfected into the microglia to inhibit activation of the microglia, so as to inhibit an inflammatory reaction after microglia mediated cerebral hemorrhage; the compound can be used for preparing microglia mediated anti-inflammatory drugs, and has good development and application prospects in the field of cerebral hemorrhage treatment.

The invention discloses a targeting polypeptide-gene composite. The composite is formed by a binding fusion protein of HIV-Tat (49-57) peptide (RKKRRQRRR) (Human Immunodeficiency Virus Trans-activator of Transcription) and V9 peptide (LTQQMKFVV) and an HIF-1alphashRNA (Hypoxia Inducible Factor-1alpha Short Hairpin Ribonucleic Acid) carrier by means of electrostatic interaction; the composite can use the guide effect of the V9 (CX3C-chemokine receptor 1) receptor on the surface of microglia, and, at the same time when the V9 peptide and the CX3CR1 receptor act with each other, the HIF-1alphashRNA is efficiently transfected into the microglia to interfere with the HIF-1alpha (Hypoxia Inducible Factor-1alpha) expression and inhibit the microglia activation so as to further inhibit the occurrence and progression of a microglia-mediated central nervous system disease. The composite can be applied to the preparation of a medicine for treating the microglia-mediated central nervous system disease and has good development and application prospect in the field of treating the nervous system disease.

The present invention concerns modulators of the CX3CR1 receptor. More specifically, antagonists and agonists of the CX3CR1 receptor have been identified. These antagonists and agonists can be used for treating an inflammatory disorder, an autoimmune disorder, a cardiovascular disease, a neurodegenerative disease, a graft versus host disease, a behavioral disorder, a cicatrisation disorder, a viral infection, cancer or pain. They may also be used as an adjuvant in a vaccine composition.

Described are biomarkers and associated methods for identifying a subject having, or at risk of developing, severe illness from influenza. The level of one or more biomarkers in a test sample from the subject is determined and compared to a control level. Optionally, the subject has or is suspected of having H1N1 influenza. In some embodiments the biomarkers may include IL23R, IL10, TNFRSF13B, CX3CR1, CCR2, MAP2K3 and / or IRF1. In some embodiments, the biomarkers include a combination of IL2 and IL23R or IL10 and IL23R. Also described are methods which include determining the level of two or more biomarkers in a sample and multivariate methods are used for comparing the levels in the test sample to the level in a control sample.

The invention provides compounds that are fractalkine receptor agonists and useful in treating, preventing or minimizing metastasis in a subject diagnosed with cancer. The compounds of the invention are further useful in treating central nervous system diseases (such as, but not limited to, HIV Associated Neurocognitive Disorders (HAND), and / or Alzheimer's disease), pain, inflammation (such as, but not limited to, arthritis), cardiovascular disease (such as, but not limited to, undesired vascular smooth muscle proliferation, atherosclerosis, coronary vascular endothelial dysfunction, and / or coronary artery disease), and / or multiple sclerosis.

The invention discloses a miR-3OB (Micro-Ribonucleic Acid-30b) composite of targeting microglia. The composite is formed by binding a fusion peptide of K9 peptide (KKKKKKKKK) and S9 peptide (VVMKFLTQQ) and the miR-30b by means of electrostatic interaction; the composite can use the guide effect of the S9 peptide to specifically target a specific CX3CR1 receptor on the surface of the microglia, and at the same time when the S9 peptide and the CX3CR1 receptor act with each other, the miR-30b is efficiently transfected into the microglia to inhibit the microglia activation so as to further inhibit the occurrence and progression of a microglia-mediated central nervous system disease. The composite can be applied to the preparation of a medicine for treating the microglia-mediated central nervous system disease and has good development and application prospect in the field of treating the nervous system disease.

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer. The compositions and methods described herein can be used, for example, to determine the propensity of a patient to benefit from treatment with a PD-L1 axis binding antagonist and to treat such patients accordingly. Using the compositions and methods of the disclosure, a patient, such as a human cancer patient, may be determined to be likely to benefit from treatment with a PD-L1 axis binding antagonist if the patient exhibits an elevated pre-treatment expression level of one or more of CST7, NKG7, GZMH, MT-ND4, HLA-H, CCL5, CD8A, CMC1, CD8B, HCST, MT-CYB, MT-ND4L, KLRG1, MT-CO2, MT-ATP6, PLEK, CTSW, HLA-C, LYAR, LITAF, GZMB, KLRD1, FGFBP2, KLRC4-KLRK1, KLRK1, B2M, GZMA, ID2, CX3CR1, PRSS23, GNLY, PRF1, and PATL2. Exemplary PD-L1 axis binding antagonists that may be used in conjunction with the compositions and methods of the disclosure are PD-L1 binding antagonists, such as anti-PD-L1 antibodies and antigen-binding fragments thereof, including atezolizumab, as well as PD-1 binding antagonists, such as anti-PD-1 antibodies and antigen-binding fragments thereof.

The present disclosure features CX3CR1 hemizygous and / or homozygous defective cells and methods of using such cells for the treatment of a metabolic or neurological disorder. The disclosed methods include methods for making and modifying CX3CR1 hemizygous and / or homozygous defective cells, such as hematopoietic stem progenitor cells. Other disclosed methods include methods of treating a subject having or suspected of having a metabolic or neurological disease comprising administering to the subject a composition comprising a hemizygous and / or homozygous defective CX3CR1 cell. The CX3CR1 hemizygous and / or homozygous defective cell may be modified to have a nucleic acid molecule encoding a therapeutic polypeptide or polynucleotide.

A therapeutic agent for an inflammatory disease comprising an antibody or a CX3CR1 antagonist that inhibits an interaction of fractalkine and CX3CR1 is provided.

The invention provides a construction method of a CX3CR1 gene humanized non-human animal. The nucleotide sequence for encoding a human CX3CR1 protein is introduced into a non-human animal genome in ahomologous recombination manner, the humanized CX3CR1 protein can be normally expressed in the animal body, the animal body can be used as an animal model for human CX3CR1 signal mechanism research and tumor and immune disease drug screening, and the important application value is realized on the research and development of new drugs of immune targets. The invention also provides a humanized CX3CR1 protein, a humanized CX3CR1 gene, a targeting vector of the CX3CR1 gene, the non-human animal obtained with the construction method and an application of the non-human animal in the field of biological medicines.

There is provided a compound of formula (I), wherein R1, R2, Q1 and formula (X) are as defined herein, which compounds are useful in the treatment of diseases and disorders associated with elevated levels of CX3CR1 and / or CX3CL1, in particular acute and / or chronic inflammation, eye diseases, lung diseases, skin diseases, joint and / or bone diseases, autoimmune diseases, cardiovascular diseases, metabolic diseases, brain diseases, neurodegenerative diseases, pain, cancer, liver diseases, kidney diseases, gastrointestinal diseases, human immunodeficiency virus and mood disorders.

The invention relates to methods and compositions for regulation of neurological conditions. In particular, methods and compositions for the modulation of the chemokine receptor 1 (CX3CR1) and its ligands are described.

Diagnostic, prognostic, and treatment methods, compositions, and kits for enhancing insulin secretion and beta cell numbers and functions, and controlling glycemia associated with diabetes, obesity, atherosclerosis, stroke, myocardial infarction, and other cardiovascular diseases, by modulating FKN / CX3CR1 expression levels or activities, and its downstream signaling pathways in a subject in need or at risk.

The present disclosure features CX3CR1 hemizygous and / or homozygous deficient cells and methods of using such cells for the treatment of metabolic or nervous system disorders. The disclosed methods include methods for preparing and modifying CX3CR1 hemizygous and / or homozygous deficient cells, such as hematopoietic stem progenitor cells. Other disclosed methods include methods of treating a subject suffering from or susceptible to a metabolic disease or a neurological disease, comprising administering to the subject a composition comprising hemizygous and / or homozygous deficient CX3CR1 cells. The CX3CR1 hemizygous and / or homozygous deficient cells may be modified to have a nucleic acid molecule encoding a therapeutic polypeptide or polynucleotide.

The invention provides a method for constructing a CX3CR1 gene humanized non-human animal, which uses homologous recombination to introduce the nucleotide sequence encoding human CX3CR1 protein into the non-human animal genome, and the animal can normally express human The CX3CR1 protein can be used as an animal model for human CX3CR1 signaling mechanism research, tumor and immune disease drug screening, and has important application value for the development of new drugs for immune targets. The present invention also provides a humanized CX3CR1 protein, a humanized CX3CR1 gene, a CX3CR1 gene targeting vector, and the non-human animal obtained by the above construction method and its application in the field of biomedicine.

The subject invention pertains to the use of fractalkine (FKN, CX3CL1) and its receptor CX3CR1 for treatment of neuroinflammation and / or neurodegeneration. In one embodiment, the present invention provides a method for treatment of neuroinflammation and / or neurodegenerative diseases, comprising: administering, to cells of a subject in need of such treatment, an adeno-associated virus that comprises a functional fractalkine gene operably linked to transcriptional control elements. In one embodiment, the subject invention is used to treat or ameliorate Parkinson's disease. The present invention can also be used to treat or ameliorate neuroinflammatory and / or neurodegenerative diseases including, but not limited to, Alzheimer's disease, epilepsy, aging, and traumatic brain injury.

The invention discloses a TLR4 (Toll-like receptor) compound of targeting microglia as well as a preparation method and application of the compound in the pharmaceutical field, and belongs to the field of biomedicine. The compound is formed by binding fusion peptide of Q9 peptide (QQQKKKKKK) and T9 peptide (LTQQVVMKF) and TLR4RNAi through an electrostatic interaction; through a guiding function of the Q9 peptide, the compound can specifically target a specific CX3CR1 receptor on the surface of the microglia; when the T9 peptide acts with the CX3CR1 receptor, the TLR4RNAi is efficiently transfected into the microglia to inhibit activation of the microglia, so as to inhibit an inflammatory reaction after microglia mediated cerebral hemorrhage; the compound can be used for preparing microglia mediated anti-inflammatory drugs, and has good development and application prospects in the field of cerebral hemorrhage treatment.

The disclosure provides compounds of formula (I) having the structure:Compounds of formula (I) are fractalkine receptor agonists and useful in treating, preventing or minimizing metastasis in a subject diagnosed with cancer. The compounds of the invention are further useful in treating central nervous system diseases (such as, but not limited to, HIV Associated Neurocognitive Disorders (HAND), and / or Alzheimer's disease), pain, inflammation (such as, but not limited to, arthritis), cardiovascular disease (such as, but not limited to, undesired vascular smooth muscle proliferation, atherosclerosis, coronary vascular endothelial dysfunction, and / or coronary artery disease), and / or multiple sclerosis.

The invention discloses an miR-21 (microRNA) compound of a target microglial cell, which is formed by combining a fusogenic peptide of a K9 (KKKKKKKKK) peptide and an S9 peptide (VVMKFLTQQ) with miR-21 through the electrostatic interaction. The compound can utilize a guide action of the S9 peptide, and performs specific targeting on specificity of a CX3CR1 accepter on the surface of the microglial cell, and when the S9 peptide acts with the CX3CR1 accepter, the miR-21 is efficiently transfected into the microglial cell at the same time, inhibits activation of the microglial cell, and further inhibits occurrence or deterioration of a central nervous system disease mediated by the microglial cell. The miR-21 compound can be used for preparing a drug for treating the central nervous system disease mediated by the microglial cell, and has a good development and application prospect in the field of nervous system disease treatment.

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer. The compositions and methods described herein can be used, for example, to determine the propensity of a patient to benefit from treatment with a PD-L1 axis binding antagonist and to treat such patients accordingly. Using the compositions and methods of the disclosure, a patient, such as a human cancer patient, may be determined to be likely to benefit from treatment with a PD-L1 axis binding antagonist if the patient exhibits an elevated pre-treatment expression level of one or more of CST7, NKG7, GZMH, MT-ND4, HLA-H, CCL5, CD8A, CMC1, CD8B, HCST, MT-CYB, MT-ND4L, KLRG1, MT-CO2, MT-ATP6, PLEK, CTSW, HLA-C, LYAR, LITAF, GZMB, KLRD1, FGFBP2, KLRC4-KLRK1, KLRK1, B2M, GZMA, ID2, CX3CR1, PRSS23, GNLY, PRF1, and PATL2. Exemplary PD-L1 axis binding antagonists that may be used in conjunction with the compositions and methods of the disclosure are PD-L1 binding antagonists, such as anti-PD-L1 antibodies and antigen-binding fragments thereof, including atezolizumab, as well as PD-1 binding antagonists, such as anti-PD-1 antibodies and antigen-binding fragments thereof.