29 results about "CXCR3" patented technology

Provided are a CAR-T cell having good blood-brain barrier permeability, a product, and a use. On the basis of the research on CAR-T cell therapy for central nervous system diseases, provided are a CAR-T cell having good blood-brain barrier permeability and a corresponding drug, for use in treating or relieving central nervous system diseases. Such a CAR-T cell uses a B cell maturation antigen as a target, and highly expresses a CXCR3 chemokine receptor and CCL1, CCL3 and CCL4 chemokines. Also provided is a product for testing and determining the blood-brain barrier permeability of the CAR-T cell, e.g., a probe, a reagent, and a kit, thereby accurately testing and determining the blood-brain barrier permeability of a certain CAR-T cell.

The present disclosure relates to CXCR3 ligands having CXCR3-expressing-cell migration-inducing activity, and specifically to amino acid modifications and amino acid sequences that are important for CXCR3-expressing-cell migration-inducing activity.

The invention relates to application of a monocarboxylic acid transporter 1 inhibitor in preparation of a medicine for preventing, relieving and / or treating pancreatic cancer. By using the MCT1 inhibitor, the lactic acid level in the pancreatic stellate cells PSCs is effectively reduced, so that the lactic acid of Vps34 is inhibited, and the activation process of autophagy-dependent PSCs mediated by the lactic acid is blocked. By inhibiting the activation of the PSCs, the MCT1 inhibitor further reduces the secretion of downstream chemokines CXCL9 and CXCL10. The CXCL9 and the CXCL10 are key factors for inducing CD8 + T cells to up-regulate PD-1 expression through CXCR3 and STAT3 signal channels, so that the MCT1 inhibitor substantially cuts off an induction signal causing CD8 + T cell depletion on the upstream, further, the in-vivo growth and in-situ tumorigenesis ability of pancreatic cancer can be inhibited, and the purpose of preventing, relieving and / or treating pancreatic cancer is achieved.

Chimeric antigen receptors that bind to CD24, optionally further including CXCR3 or IL-15, and optionally further including EGFRt, polynucleotides encoding the receptors, cells comprising the polynucleotides, and methods of treating cancers using said chimeric antigen receptors or cells are disclosed.

This provides the crystalline form of piperazinyl-thiazole derivatives. [Solution] The present invention relates to the crystalline form of 1-{(R)-2-(2-hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethylpyrimidine-5-yl)-thiazole-5-yl]-piperazine-1-yl}-2-(3-methyl-[1,2,4]triazole-1-yl)-ethanone, a method for producing the same, a pharmaceutical composition having the crystalline form, a pharmaceutical composition produced from the crystalline form, and the use of the same as a CXCR3 receptor modulator in the treatment of various diseases and disorders related to the CXCR3 receptor and its ligands.

The application provides a method, device, medium and program product for assisting in predicting immune-related adverse reactions, and relates to the field of intelligent medical treatment. The method comprises the following steps: acquiring cell data of a subject; calculating the proportion of target cell subgroups including a CXCR3+CCR6+CD8+T cell subgroup and an NK cell subgroup in single nucleus cells based on the cell data; calculating a prediction score based on the proportion of the target cell subgroups; and outputting an auxiliary prediction result of the probability of the subject suffering from an immune-related adverse reaction according to the prediction score. It is explored and verified in the application that a higher baseline level of the CXCR3+CCR6+CD8+T cell subgroup and the NK cell subgroup in immunotherapy is closely related to the occurrence of irAE.

The invention relates to an application of a soluble epoxide hydrolase inhibitor in the field of transplantation, the soluble epoxide hydrolase inhibitor is TPPU, and the soluble epoxide hydrolase inhibitor is applied in the fields of organ transplantation and tissue transplantation. The TPPU is used for relieving allogeneic mouse heart and skin transplantation immunological rejection, reducing immune cell infiltration in transplantation operation, and inhibiting CD4 + T cell proliferation, CXCR3 chemokine receptor positive and Th1 cell subset proportion. The TPPU inhibits proliferation of primary CD4 + T cells of normal mice and differentiation of Th1 cell subgroups. In organ transplantation and tissue transplantation, the invention provides a single soluble epoxide hydrolase inhibitor TPPU, which can relieve allogeneic mouse heart and skin transplantation immunological rejection, inhibit normal mouse primary CD4 + T cell proliferation and differentiation, and reduce toxic and side effects caused by the use of an immunosuppressant.

To provide cleavable activators of CXCR3 and methods of use.SOLUTION: Disclosed is a recombinant C-X-C motif chemokine ligand (CXCL) peptide modified to introduce a cleavage site for a protease (e.g., a protease that is activated during an inflammation response). The CXCL peptide has an ability to activate CXCR3 until the protease cleaves the peptide. The proteolytic cleavage of the CXCL peptide minimizes pro-inflammatory response and inhibits the development of fibrosis. The CXCL may be CXCL10, CXCL4, CXCL9 or CXCL11.SELECTED DRAWING: None

An antigen binding protein targeting CXCR3 and the use thereof. The antigen binding protein can specifically bind to CXCR3. The antigen binding protein contains a heavy chain variable region, and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3.

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 present disclosure relates to CXCR3 ligands having resistance to DPPIV and having CXCR3-expressing cell migration-inducing activity. The present disclosure specifically relates to N-terminal amino acid modifications and N-terminal amino acid sequences important for resistance to DPPIV and CXCR3-expressing cell migration-inducing activity.

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.

Disclosed are nucleic acid constructs encoding CXCR3 and a CAR and cells containing same for the treatment of cancers.

The invention relates to the field of immunology and cell therapy, in particular to application of rTh1 cells in preparation of drugs for preventing or treating allergic diseases or inflammatory diseases, the phenotypes of the rTh1 cells are CD3 (+), CD4 (+), CD25 (-), Foxp3 (-), CXCR5 (-), CCR6 (-), CXCR3 (+), CD73 (+) and cMaf (+), and FR4, PD1 and ICOS are highly expressed. The novel T cell subset rTh1 cell has an immunoregulation function, and has an important value in prevention and treatment of allergic diseases such as food allergy and dust mite allergy, atopic dermatitis, allergic asthma, chronic obstructive pulmonary disease and other Th2-type inflammation related skin diseases such as pemphigus bullosa and urticaria.

The application belongs to the technical field of biological medicine, and particularly relates to the use of SH2 domain-containing protein tyrosine phosphatase 1 (SHP1) in the preparation of a drug for treating chronic pain, in particular to the use of SHP1 in the preparation of a drug for treating chronic pain by regulating the morphology of spinal cord astrocytes, the integrity of the blood-spinal cord barrier and the STAT1-CXCL10-CXCR3 neuroimmune signal axis, and a chronic pain treatment strategy based on the signal axis. The application first discloses that SHP1 in spinal cord astrocytes directly dephosphorylates STAT1, inhibits the transcription of CXCL10 and the subsequent infiltration of T lymphocytes into the spinal cord, and discloses the core analgesic mechanism, thereby establishing SHP1 as a new target for treating chronic pain, and opening up a new way for the precise treatment of clinical chronic pain, especially neuropathic pain.

[Problem] To provide a means for promoting the proliferation of at least one type of cells that are included in effector T cells and are selected from CD4+ T cells having an expression pattern of cell surface markers of CXCR3+ / CCR4low / CCR6high, MAIT cells, and NKT cells. [Solution] Provided is: a composition for promoting the proliferation of (i) CD4+ T cells having an expression pattern of cell surface markers of CXCR3+ / CCR4low / CCR6high and (ii) MAIT cells and / or NKT cells; or a composition for treating a disease or condition that is ameliorated by the proliferation of at least one type of cells selected from CD4+ T cells having an expression pattern of a cell surface marker of CXCR3+ / CCR4low / CCR6high, MAIT cells, and NKT cells. Each of the compositions contains an exopolysaccharide from lactic acid bacteria.

Artificial expression constructs encoding a CXCR3 isoform and a recombinant receptor are described. The artificial expression constructs include the CXCR3 isoform: CXCR3-A, CXCR3-B, or CXCR3-alt, and are used to enhance the tumor trafficking of cells engineered to express the artificial expression construct. The artificial expression constructs and engineered cells disclosed herein can be used in the treatment of B7-H3-expressing cancers, such as diffuse intrinsic pontine glioma.

The present invention relates to a pharmaceutical combination comprising a first active ingredient which is the CXCR3 antagonist 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof, and a second active ingredient which is an anti-CD3 monoclonal antibody (mAb); and to the use of the pharmaceutical combination in the prevention, prophylaxis and / or treatment of (auto-)immune / inflammatory mediated disorders, including type 1 diabetes (T1D) (especially autoimmune T1D), multiple sclerosis, organ transplant rejection (especially renal and heart allograft rejection), thyroid eye disease, rheumatoid arthritis, ulcerative colitis, crohn's disease, celiac disease, atherosclerosis, psoriasis, lung inflammation, and psoriatic arthritis.

The invention belongs to the technical field of biology, and particularly relates to a composition for improving the developmental potential of oocytes, an in-vitro maturation culture solution and an optimized culture method. And a CCR5 / CXCR3 antagonist. The preparation for in-vitro embryo production contains an Ephrin ligand family and a CCR5 / CXCR3 antagonist, the microenvironment for maturation culture of oocytes is synergistically optimized, further, sesquiterpenol compounds and / or phenylpropane compounds can be added on the basis, and therefore the preparation can be used for preparing the embryos in vitro by means of the synergistic effect of the components. The composition can effectively inhibit the formation of abnormal protein aggregates in oocytes, enhance the ability of proteasomes to remove error protein aggregates, significantly reduce the level of reactive oxygen species (ROS) and increase the content of endogenous antioxidant substances such as glutathione (GSH), so as to reduce the protein toxicity stress, oxidative stress and other dimensions, and thus, the composition can be used for preparing an anti-inflammatory drug. The quality and the fertilization rate of oocytes after in-vitro maturation and the development potential of subsequent embryos are remarkably improved, and the application prospect is wide.

Disclosed is a CAR-T cell with good blood-brain barrier permeability, a product, and use thereof, relating to the technical field of treatment of central nervous system diseases. Based on the study on CAR-T cell immunotherapy for central nervous system diseases, this disclosure provides a CAR-T cell with good blood-brain barrier permeability and a corresponding drug for treating or improving the central nervous system diseases. The CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4. This disclosure further provides a product for detecting and judging the blood-brain barrier permeability of the CAR-T cell, such as probes, reagents, and kits, which can accurately detect and judge the blood-brain barrier permeability of a specific CAR-T cell.

Methods of treating a subject with cancer with CD8 T cell-mediated immune therapy are provided. The methods include measuring an amount of CXCR3-positive T cells in a peripheral blood sample or a tumor sample from a subject with cancer following treatment of the subject with at least one dose of the CD8 T cell-mediated therapy and comparing the amount of CXCR3-positive T cells in the sample to a control. Responsiveness of the cancer to the CD8 T cell-mediated therapy is predicted based on whether there is an increase or decrease in the amount of CXCR3-positive T cells in the sample. Methods further including treating the subject with at least one additional dose of the CD8 T cell-mediated immune therapy are also provided.

The application discloses a research method for the mechanism of CXCR3A in acute respiratory distress syndrome, and relates to the technical field of biomedicine; and comprises the following steps: establishing an animal ARDS model and setting an intervention group; experiment animals are randomly divided into at least four groups, namely a normal control group, an ARDS model group, a CXCR3 broad-spectrum inhibitor intervention group and a CXCR3A selective inhibitor intervention group; a damaging agent is applied to the model group and the two inhibitor intervention groups of animals to establish an ARDS model; the CXCR3 broad-spectrum inhibitor intervention group and the CXCR3A selective inhibitor intervention group are respectively pretreated with corresponding inhibitors before modeling. The method of the application constructs a complete research framework from the whole animal level to the molecular level, covers multiple key aspects of pathological morphology, inflammatory response, oxidative stress and target gene expression, and can reveal the comprehensive mechanism of CXCR3A in the occurrence and development of ARDS.

The invention provides a method for predicting the susceptibility of a patient suffering from a cancer or a myeloid-mediated disease to immunotherapy. Furthermore, the invention provides a method for treating a patient suffering from a cancer or a myeloid-mediated disease with immunotherapy. In accordance with these embodiments, the inventive method includes assaying myeloid cells obtained from the patient prior to treatment for the expression of CXCR3. The invention also provides a genetically engineered myeloid cell (GEMy) in which the expression of CXCR3 is modulated (up- or down-regulated). The invention further provides a composition comprising the inventive GEMy and a pharmaceutically acceptable carrier. The invention also provides a method for treating a patient in need of immunotherapy comprising administering the inventive composition to a patient.

The present disclosure provides nucleic acids encoding transforming growth factor inhibitors and IL-12. Further, nucleic acids encoding the chemokine receptor CXCR3 are provided herein. Additionally, oncolytic viruses comprising the nucleic acids described herein are described herein. The compositions described herein are further described for use in the treatment of cancer. Described herein is a composition comprising a vector, the vector comprising an exogenous nucleic acid comprising a sequence encoding a cytokine or a functional variant thereof, an exogenous nucleic acid comprising a sequence encoding a chemokine receptor or a functional variant thereof, and a first promoter region upstream of the sequence encoding the chemokine receptor, causing expression of the chemokine receptor before expression of the cytokine.

The present application relates to an antigen binding protein targeting CXCR3 and its use, the antigen binding protein can specifically bind CXCR3, comprising a heavy chain variable region and a light chain variable region. The present application also provides a preparation method of the antigen binding protein and its use.

A novel anti-human CXCR3 antibody useful for antibody drugs is provided. Provided is an antibody that specifically binds to human CXCR3, specifically binds to the extracellular domain of human CXCR3A, has activity to block CXCR3A-dependent cellular functions, and does not specifically bind to human vascular endothelial cells. The antibody has heavy chain CDR1 to 3 and light chain CDR1 to 3 containing specific amino acid sequences. The antibody is preferably a humanized antibody or a chimeric antibody.

Interferon-γ-inducible protein 10 (IP-10) peptides, IP-10 peptide variants and in silico designed C-X-C chemokine receptor 3 (CXCR3) peptide agonists are described. The small peptides can be used for inhibiting pathological tissue remodeling and treating fibrosis in a subject, such as a subject with fibrosis of the heart, lung, liver, kidney or skin. The peptide agonists can also be used to treat cardiovascular disease, including myocardial infarction and ischemia-reperfusion injury. Also described are in silico designed peptide antagonists that bind CXCR3 or ligands of CXCR3. These antagonist peptides block CXCR3 signaling by disrupting interaction of CXCR3 with its ligand. Antagonist peptides can be used, for example, to treat myocarditis and atherosclerosis. In additional embodiments agonists and antagonists of CXCR4 are disclosed.

The present invention provides a novel anti-human CXCR3 antibody useful in antibody drugs. The present invention provides an antibody that specifically binds to human CXCR3, which antibody specifically binds to the extracellular domain of human CXCR3A, has an activity of blocking CXCR3A-dependent cellular functions, and does not specifically bind to human vascular endothelial cells. The antibody has heavy chain CDR1 to 3 and light chain CDR1 to 3 comprising specific amino acid sequences. The antibody is preferably a humanized antibody or a chimeric antibody.

The present application relates to the use of platelet factor 4 in the preparation of a drug for treating or preventing Candida albicans infection, platelet factor 4 acts on macrophage CXCR3 receptor, antagonizes Candida albicans induced macrophage PANoptosis, thereby reducing the damage of Candida albicans to macrophages, maintaining the survival and normal function of macrophages, enhancing the clearance ability of the body to Candida albicans, reducing the inflammatory response caused by infection, reducing pathological damage, and different from the treatment mechanism of traditional antifungal drugs, the present application does not directly act on fungi, which helps to reduce the formation of drug-resistant strains and the toxic side effects such as liver toxicity and kidney toxicity caused by antifungal drugs, and can provide a more optimal new treatment mode for clinical Candida albicans infection.