82 results about "CXCR4" patented technology

The invention discloses a preparation method and application of a novel hybrid extracellular vesicle. According to the invention, vesicles derived from endothelial cells and neutrophil cells are combined with deferoxamine, and a biological mixed nano vesicle platform (DFO (HEVS)) is developed to solve the problem of diabetes wound healing. According to the dual-targeting system, DFO is accurately delivered to a wound part by utilizing CXCR4 mediated endothelial cell homing and beta2 integrin dependent inflammation tropism, DFO (at) HEVs activates and recovers vascular regeneration through HIF-1alpha / VEGF, ferroptosis is inhibited through Nrf2 / GPX4 signal transduction, macrophages are reprogrammed into a repair promoting M2 phenotype, and oxidative stress-inflammation-ferroptosis circulation is effectively broken.

The invention discloses a multichannel tissue-derived neutrophil detection chip and an application system, the chip is a multichannel detection chip integrating migration-related markers and functional markers, rapid and synchronous identification of neutrophil tissue sources is realized, the migration-related markers are CD62L and CXCR4, the functional markers are CD44 and MPO, and the migration-related markers are CD62L and CXCR4. According to the method, migration related markers and functional state markers are subjected to integrated and collaborative analysis, tissue sources are locked from the cell state and function two dimensions, four-channel parallel detection is performed, and the tissue sources of the neutrophil are accurately judged through expression profile modes of the four components instead of a single marker, so that the neutrophil detection accuracy is improved. According to the method, the neutrophil tissue source is rapidly, synchronously and accurately identified, the technical bottleneck of neutrophil tissue source detection is broken through, high efficiency, accuracy and universality are achieved, and an efficient and accurate tool is provided for immune mechanism research and clinical diagnosis.

The present invention relates to antibodies or antigen binding fragments thereof that specifically bind to CXCR4. The invention also relates to said antibodies for use in therapy, in the treatment of cancer, and in the treatment of solid tumors. The invention also relates to pharmaceutical compositions comprising said antibodies, nucleic acids encoding said antibodies, vectors comprising said nucleic acids, and host cells comprising said nucleic acids or vectors.

The invention provides in-situ forming fluid bionic hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides an injectable GelSSO / PDA (at) SDF fluid bionic niche, after in-situ photo-crosslinking, preferential and sustained release of PDA (at) SDF NPs initiates early signal amplification, which recruits EPCs and MSCs through an SDF-1 alpha / CXCR4 axis, promotes activation of the angiogenic vascular niche through an AKT signal, and repolarizes macrophages to a regenerated M2 phenotype. Subsequently, the gradual degradation of the bionic niche triggers the stable release of SSO, and the later signal is further amplified to form an osteogenic niche with transcriptional activity, thereby maintaining the MAPK / ERK-mediated MSCs osteogenic differentiation. The fluid bionic niche can form a niche conforming to defects through photopolymerization, the local immune imbalance and endogenous progenitor cell recruitment are corrected in the early stage, then formation of new vessels and lamellar bones is promoted, and finally vascularization regeneration of diabetic skull defects is achieved.

The present invention provides CXCR4 inhibitors of formula (I) and pharmaceutically acceptable salts thereof, as well as methods of using them in the treatment of neurological and CNS diseases, disorders, and conditions. The provided compounds are inhibitors of CXCR4 and are therefore useful for treating one or more disorders associated with CXCR4 activity. Thus, in certain embodiments, the present invention provides a method for treating a CXCR4-mediated disorder, comprising administering to a patient in need thereof a CXCR4 inhibitor described herein, such as a compound of formula I or a pharmaceutically acceptable salt thereof. Certain embodiments of the present invention are directed to the use of CXCR4 inhibitors that, when administered to a subject, cross the blood-brain barrier (BBB) ​​and enter the brain and central nervous system (CNS). JPEG2026502774000083.jpg3135

The invention discloses a double-gene engineered mesenchymal stem cell and application thereof, and relates to the technical field of biological medicines. According to the double-gene engineered mesenchymal stem cell provided by the invention, CXCR4 and TNFSF14 proteins are co-expressed by the mesenchymal stem cell, and the mesenchymal stem cell shows enhanced tumor tropism and immune-mediated anti-tumor activity. Specifically, based on the principles that CXCR4 can enhance the active homing ability of mesenchymal stem cells to gastric cancer lesions expressing ligands SDF-1 (SDF-1 / CXCL12) of the mesenchymal stem cells, TNFSF14 (LIGHT can interact with HVEM and LT betaR receptors to promote activation of T cells and NK cells and the like, the mesenchymal stem cells co-expressing CXCR4 and LIGHT overcome the defects that natural MSCs are insufficient in targeting ability and weak in immune activation ability; the excellent anti-tumor effect is realized.

The application belongs to the technical field of biological medicine, and relates to application of a CXCL14 inhibitor in preparation of a drug for preventing or treating abdominal aortic aneurysm of a patient. The inhibitor effectively eliminates the gender difference of abdominal aortic aneurysm by specifically blocking the combination of CXCL14 and its receptor CXCR4, significantly reduces aortic macrophage infiltration and PDGFRA + macrophage accumulation in the progress of abdominal aortic aneurysm, reduces the degree of collagen degradation and elastic fiber damage, and thus inhibits the pathological progress of abdominal aortic aneurysm. The application provides a new target and drug combination for precise treatment of male abdominal aortic aneurysm, and has clear clinical application value.

The application discloses double-gene engineered mesenchymal stem cells and application thereof, relates to the technical field of biological medicine. The double-gene engineered mesenchymal stem cells provided by the application co-express CXCR4 and TNFSF14 proteins, exhibit enhanced tumor tropism and immune-mediated anti-tumor activity. Specifically, based on the principle that CXCR4 can enhance the active homing ability of mesenchymal stem cells to gastric cancer lesions expressing its ligand SDF-1 (SDF-1 / CXCL12), and TNFSF14 (LIGHT) can interact with HVEM and LTbetaR receptors to promote the activation of T cells and NK cells, the mesenchymal stem cells co-expressing CXCR4 and LIGHT overcome the defects of insufficient targeting of natural MSCs and weak immune activation ability, and have excellent anti-tumor effect.

The application belongs to the technical field of biological medicine, and provides a CXCR4 high expression type iPSC-NK cell with enhanced bone marrow and tumor tissue homing ability, and a preparation method and application thereof. The cell takes pluripotent stem cells as starting cells, overexpresses a membrane-bound IL-15 and IL-15RA fusion protein gene and a CXCR4 receptor gene in the pluripotent stem cells; pluripotent stem cells stably expressing the target gene are obtained, and then iPSC-NK cells are obtained through induction differentiation. The membrane-bound IL-15 and IL-15RA fusion protein gene and the CXCR4 receptor gene are targetedly integrated into a safe harbor site of the induced pluripotent stem cell through a gene editing technology, so as to construct an iPSC cell strain stably expressing key proteins; the function-enhanced iNK cell is obtained through induction differentiation, and exhibits excellent bone marrow and various solid tumor tissue homing ability and persistent immune killing activity.

The present invention relates to a cell population of spiral ganglion neural progenitors (SGNPs) and methods how to isolate these cells from an in-vitro mixed cell population. The cell population expresses one or more markers, wherein the one or more marker is CXCR4, SUSD2, LPAR3, EPHA5, CHRNA3, REEP1, NPFFR2, SORCS3, NFASC, GABRB3, KCNB2, GRM8, DLL3, and / or KCNH8.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

This invention belongs to the field of protein engineering and biomedicine, and particularly relates to a water-soluble membrane protein, a recombinant vector, a recombinant host bacterium, and their modification methods and applications. The method involves the following steps: First, an interface mutant is constructed based on the SQTY code, and its water solubility and ligand binding ability are evaluated. If the requirements are not met, multiple low-impact transmembrane regions are screened, and after mutation modification, the interface mutant is introduced to construct a single-transmembrane combined mutant, whose water solubility and ligand binding ability are evaluated. If the requirements are still not met, the multiple low-impact transmembrane regions are combined in pairs, and the interface mutant is introduced to construct various double-transmembrane combined mutants, whose water solubility and ligand binding ability are evaluated, and the optimal double-transmembrane combined mutant is selected. This method rationally mutates CXCR4 in stages to achieve water solubility, minimizing changes to the protein's structure and other physicochemical properties, thereby maintaining or even enhancing its binding ability to the ligand CXCL12.

The invention provides a Motixazotide-nitrogen mustard conjugate and a preparation method and application of a fluorescent probe of the Motixazotide-nitrogen mustard conjugate, and belongs to the field of polypeptide preparation and biological medicine. According to the present invention, a solid phase polypeptide synthesis method is adopted to covalently link a DNA alkylation reagent nitrogen mustard and a CXCR4 targeting peptide Motixazotide, and further couple with a fluorescent dye so as to successfully prepare a series of novel conjugates and fluorescent probes thereof; experiments prove that the Motixazotide-nitrogen mustard conjugate and the fluorescent probe thereof prepared by the invention can be used for remarkably improving the anti-tumor activity of nitrogen mustard and the targeting property of the nitrogen mustard to tumor cells. Meanwhile, the rhodamine B labeled dinitrogen mustard conjugate BCCR has a specific targeting effect on a CXCR4 receptor and a dual targeting effect on a tumor cell nucleus. The conjugate realizes real-time tracing of the whole process of tumor targeting, cell delivery and nuclear localization, and provides a powerful tool for curative effect evaluation and mechanism research, so that the conjugate has good clinical transformation prospect and application value.

This application discloses a compound or a pharmaceutically acceptable salt thereof, said compound comprising a compound of formula (I) or a compound of formula (II). A radioactive element preparation comprising thereof and a radioactive element chelated therewith is also disclosed. Its use in the preparation of reagents targeting CXCR4, particularly CXCR4 tracers, more particularly in vivo CXCR4 tracers, or reagents that specifically bind to cells expressing CXCR4 is also disclosed. [Targeting Peptide-I]-Xaa1-X 1 (R 1 )L 1 -[Connector]-R x n1 (I), R x n1 -[Connector]-X 1 (R 1 )L 1 -Xaa1-[targeting peptide-II](II).

The present invention relates to compounds and methods useful for dual inhibition of C-X-C receptor type 4 (CXCR4) and Bruton's tyrosine kinase (BTK). The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

The invention relates to the technical field of biology, in particular to a method for modular assembly of artery blood vessel type organs and construction of tissue microcirculation of the artery blood vessel type organs. The method comprises the following steps: inducing human pluripotent stem cells to differentiate through a mesoderm stage to form an arterial specific vascular organoid module (AVO), and then carrying out modular assembly on the AVO in vivo or in vitro so as to quickly reconstruct a tissue microcirculation network with arterial characteristics. The obtained artery blood vessel organoid is uniform in form, the diameter of the artery blood vessel organoid is intensively distributed at about 200 microns, SOX17 and CXCR4 artery endothelial markers are expressed at the same time, and the artery blood vessel organoid has polarity and a complete basilar membrane. Transplanting experiments show that the organ can be integrated with host blood vessels in a short time, and ischemic tissue blood perfusion is recovered. The defects that existing organoid is irregular, difficult to splice, delayed in perfusion and the like are overcome, and a new strategy is provided for revascularization and acute ischemic disease repair.

The present application discloses a kind of compound for targeting CXCR4 and purposes thereof.The compound is shown in structure of formula (I) or its isotopic variant, hydrate, ester or solvate, tautomer, stereoisomer or pharmaceutically acceptable salt.The compound of the present application connects ligand group (Ra and Rb) for targeting CXCR4 and chelating group Z by linker (L1-X-L2), which has good CXCR4 targeting and specificity, can be quickly imaged in a short time after administration, and can be used for diagnosing and treating CXCR4 overexpression diseases.

The present disclosure is based on a novel assay based on the determination of SDF-1 [alpha]-induced migration of CXCR4 primary human cells in the presence of an anti-CXCR4 polypeptide, correlating the degree of CXCR4 receptor occupancy (RO) of the anti-CXCR4 polypeptide with the efficacy of the anti-CXCR4 polypeptide. Migration inhibition as determined by an in vitro assay provides an alternative indicator of in vivo efficacy of the anti-CXCR4 polypeptide.

The invention provides a use of a marker or a combination thereof in preparation of a product for prediction, diagnosis or auxiliary diagnosis of measurable residual diseases, the measurable residual diseases occur after clinical complete remission of acute myelogenous leukemia patients, and the marker or the combination thereof comprises a C-X-C chemokine receptor 4 gene. According to the method, a multi-parameter flow sorting technology is adopted, leukemia cell populations are separated from bone marrow samples of patients in the first diagnosis stage and the AML MRD stage, and a sufficient number of residual disease cells are successfully captured through a single cell transcriptome sequencing technology. The CXCR4 low-expression cell is identified to be capable of being used as a common marker of an MRD cell, and is verified in a clinical AML patient specimen. And an innovative scheme is provided for MRD monitoring of AML patients lacking clear molecular markers. And meanwhile, a CXCR4 low-expression cell is provided as a function substitution model of the MRD cell, so that the technical limitation of insufficient residual cells in the traditional research is broken through, and a reliable research system is established for systematically exploring the biological characteristics of the MRD cell.

The present invention pertains to the nanoencapsulation of siRNA and other biologics in phospholipid nanosomes for the improved delivery of siRNA and other biologics to targeted diseased human or animal organs and human or animal cells and apparatus and methods for making the same. In embodiments of the present invention, novel siRNAs were designed to down regulate CCR5 and CD4, based on an analysis of all known alternative transcripts for each gene from both human and monkey (Macaca mulatta) genomes. Embodiments of the present invention feature supercritical, critical and near critical fluids. Embodiments of the present invention also pertain to down regulation of CXCR4 receptor and targeting of nanosomes containing specific siRNA sequences to cells expressing those receptors on the cell surface by coating them with specific ligands. These include ligands for the receptors CCR5, CD4 and CXCR4.

The invention belongs to the technical field of biological medicines, and provides a preparation method of a CAR-T cell exosome expressing CXCR4 targeting CLDN18.2. The preparation method comprises the following steps: culturing CAR-T cells co-expressing CXCR4 targeting CLDN18.2 to obtain a culture solution; separating and purifying the culture solution to obtain an exosome; wherein the culture medium contains IL-7 and IL-15. The invention provides a method for efficiently producing the CAR-T cell exosome, and the exosome production capability of the CAR-T cell is remarkably improved by adding specific cell factors. The surface of the exosome provided by the invention carries a CAR structure and CXCR4 protein unique to mother cells, has tumor homing ability and a specific killing function, and avoids toxic and side effects of living cell therapy. The exosome can significantly inhibit proliferation and metastasis of CLDN18.2 positive tumor cells, and an innovative solution is provided for solid tumor treatment.

The present invention relates to NK cells with an improved ability to target and kill cancer cells and use thereof. Specifically, the present invention relates to: iPSC-based NK cells into which a chimeric antigen receptor targeting a specific cancer antigen, CXCR4 and CCR7 genes, which are chemokine receptors, and an IL-15 / IL-15Rα (IL-15RF) gene are introduced; and use thereof for treating cancer. The iPSC-based NK cells according to the present invention can not only directly target a specific cancer antigen by the introduced CAR, but can also activate NK cells and enhance the proliferation thereof by regulating intracellular signaling and tumor microenvironment by the introduced CXCR4 and CCR7 and the introduced IL-15RF. Therefore, the NK cells into which multiple genes are introduced, according to the present invention, can efficiently target and attack cancer cells, and thus can be effectively used for the treatment of cancer diseases.

The invention relates to the technical field of immune preparations, in particular to application of Forskolin or pharmaceutically acceptable salt thereof in preparation of a vaccine immunopotentiator. Aiming at the defects of vaccine immunomodulators in the prior art, the invention provides a novel method for enhancing the immune effect of a vaccine by using a natural plant extract Forskolin (as an adenylate cyclase activator), the Forskolin can promote high expression of CXCR4 by plasma cells to obviously enhance the homing ability, the residence ability and the service life of the plasma cells, so that the immune effect of the vaccine is enhanced. Therefore, the long-term immune response of the antibody is improved. The Forskolin directly targets the effector cytoplasm cells immunized by the vaccine, so that the potential safety hazard of the traditional technology is avoided, and meanwhile, more lasting and stable immune protection is provided.

The present invention relates to the systems and methods of identifying compounds to treat or prevent chronic obstructive pulmonary disorders (COPD). The present invention also provides compositions to treat or prevent COPD comprising modulators of one or more selected from the group consisting of: AC AN, ACTN1, ADAMTS4, ADRB2, AGER, AN06, AP3B1, AP0A1, ARRB1, ATP1A1, BCL2L1, BDKRB1, BRAF, CALCRL, CCL11, CDH1, CEACAM8, CHRM3, CHRNA1, CLU, COL10A1, COL12A1, COL14A1, COL4A2, COL6A1, COL6A3, COLGATE 1, CRH, CSK, CTSD, CTTN, CXCR1, CXCR4, CXCR5, FBN1, FGA, FGG, FHL2, FTH1, GNB1, GPIHBP1, GPR84, GPR97, GRM8, HAPLN1, H2BFS, HBB, HSP90B1, ICAM1, IGF1R, IL6, ITGA1, ITGAV, LAMA2, LAMA4, LRP1, LTBP1, MAPK3, MGAM, MMP1, MMP13, MMP3, MMP9, MYBPH, MYH10, MYH9, NMU, NR3C1, P4HB, PLCB3, PLAG2G7, POU2AF1, PPIB, PROK2, RUNX2, RXFP1, S100A12, S100P, SAA1, SDC2, SLC2A5, SMAD3, SPARCL1, SPP1, SYT13, TBX1, TF, TGFB2, THBS1, TIMP1, TLN1, TPM1, TPM2, TPM4, TSPAN14, TEN, TWIST2, VIM, and WT1, and methods of use thereof.

A herpes virus vector is provided with both transcriptional and translational control. Within various embodiments the herpes virus vector is based upon a modified herpes virus and has both ICP27 and ICP34.5 under control of a CEA promoter and miRNA-124 / 143, respectively, and deletion of at least one copy of terminal repeat long region is provided to increase safety without sacrificing efficacy. The herpes virus vector can also incorporate a virus-expressed cytokine cassette encoding IL-12, IL-15 / IL-15RA under the control of CXCR4 promoter.

The present application provides compositions and methods of use for treating, preventing or ameliorating diseases, disorders or conditions associated with chemokine receptors (e.g., CXCR4).

The present invention relates to the field of medical diagnostics. In particular, it relates to methods and kits for determining treatment efficacy of allergen immunotherapy, and for measuring or detecting biomarkers in a subject undergoing allergen immunotherapy. For example, the invention provides a method of determining efficacy of an allergen immunotherapy in a subject, the method comprising: providing a first sample obtained from a subject before receiving allergen immunotherapy; providing a second sample obtained from the subject who has received, or who is receiving, allergen immunotherapy; wherein the first and second samples comprise B-cells; and determining the level or amount of one or more biomarkers in B-cells, preferably allergen-specific B-cells, in the first and second samples, wherein the biomarkers are selected from the group consisting of IgE, CD29, CD69, IL13Rα, CD99, IgD, CXCR4, FCRL3, FCRL2, FCRL5, SIGLEC10, CDIc, CD23, and IL4Rα; wherein an increase in the level or amount of one or more biomarkers selected from IgE, CD29, IL13Rα, CD99, FCRL3, FCRL2, SIGLEC10, CD1c, CD23, and IL4Rα in B-cells in the second sample compared to the first sample indicates efficacy of an allergen immunotherapy in a subject, and / or wherein a decrease in the level or amount of one or more biomarkers selected from CD69, IgD, CXCR4, FCRL3, FCRL2, FCRL5, CD1c, CD23, IL4Rα in B-cells in the second sample compared to the first sample indicates efficacy of an allergen immunotherapy in a subject.