50 results about "CXCR3" patented technology

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.

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.

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 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, or autoimmune diseases.

The assay system allows for the study of cell migration through tissue-associated extracellular matrix under chemokine gradients within a modular assay platform. Using this assay system, activated CD3+ T cells migrating towards chemokines (CXCL10 and CXCL12) and chemokine mimetics (CXCR3 agonists) were detected, quantified, and studied. This assay system facilitates drug discovery and the study of the microenvironment, stimuli, and responding cells.

The invention provides a method, equipment, a medium and a 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 tested cell data; calculating the proportion of target cell subgroups including CXCR3 + CCR6 + CD8 + T cell subgroups and NK cell subgroups in the mononuclear cells on the basis of the cell data; calculating a prediction score based on the proportion of the target cell subpopulation; and according to the prediction score, outputting an auxiliary prediction result of the probability of the immune-related adverse reactions of the subject. The application explores and verifies that the higher baseline level of the immunotherapy CXCR3 + CCR6 + CD8 + T cell subset and the NK cell subset is closely related to the occurrence of irAE.

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.

An assay system permits study of cell migration through tissue-relevant extracellular matrices under a chemokine gradient within a modular assay platform. Activated CD3+ T-cells were detected, quantified, and studied as they migrated towards chemokines (CXCL10 and CXCL12) and chemokine mimetics (CXCR3 agonist) using the assay system. Discovery of drugs, and the study of microenvironments, stimuli, and responding cells are facilitated by the assay system.

The present disclosure provides nucleic acids encoding a transforming growth factor inhibitor and IL-12. Also provided herein are nucleic acids encoding the chemokine receptor CXCR3. Additionally described herein are oncolytic viruses comprising the nucleic acids described herein. The use of the compositions described herein in the treatment of cancer is also described.

The present invention relates to a pharmaceutical combination comprising a first active ingredient, which is a 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] triazole-5-yl)-2-(3-methyl-[1, 2, 3] triazole-5-yl)-2-(3-methyl-[1, 2, 3] triazole-5-yl)-2-(3-methyl-[1, 2, 3] a second active ingredient (which is an anti-CD3 monoclonal antibody (mAb)) and a second active ingredient (which is an anti-CD3 monoclonal antibody (mAb)); the invention also relates to the application of the medicine combination in the prevention / prevention and / or treatment of (autoimmune) / inflammation-mediated conditions (including type 1 diabetes mellitus (T1D) (especially autoimmune T1D), multiple sclerosis, organ transplant rejection (especially kidney and heart allograft rejection), thyroid eye diseases, rheumatoid arthritis, ulcerative colitis, Crohn's disease, celiac disease, and the like), and also relates to the application of the medicine combination in the prevention / prevention and / or treatment of (autoimmune) / inflammation-mediated conditions (including type 1 diabetes mellitus (T1D) (especially autoimmune T1D), multiple sclerosis, organ transplant rejection (especially kidney and heart allograft rejection), thyroid eye diseases, rheumatoid arthritis, ulcerative colitis, Crohn's disease, celiac disease and the like. The traditional Chinese medicine composition can be used for treating psoriasis, atherosclerosis, psoriasis, lung inflammation and psoriatic arthritis

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.

An assay system permits study of cell migration through tissue-relevant extracellular matrices under a chemokine gradient within a modular assay platform. Activated CD3+ T-cells were detected, quantified, and studied as they migrated towards chemokines (CXCL10 and CXCL12) and chemokine mimetics (CXCR3 agonist) using the assay system. Discovery of drugs, and the study of microenvironments, stimuli, and responding cells are facilitated by the assay system.

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.

The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.

Methods are disclosed for treating a subject with an autoimmune disease. These methods include selecting a subject with the autoimmune disease that has i) an increase in ABC, DN1 cells, DN2 cells, DN3 cells and / or plasmablasts in a blood sample obtained from the subject as compared to control subjects, and / or ii) an increase of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-SM antibodies as compared to a control, and administering to the subject an effective amount of IL-12 antagonist. Methods are disclosed for selecting a subject with an autoimmune disease that can be treated with an IL-12 antagonist. In some aspects, the autoimmune disease is systemic lupus erythematosus (SLE) or Sjogren's syndrome. Compositions including a therapeutically effective of an IL-12 antagonist for use in these methods are also disclosed.

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.

Recombinant C-X-C motif chemokine ligand (CXCL) peptides are described that are modified to introduce proteases, such as cleavage sites of proteases that are activated during inflammatory responses. The CXCL peptide has the ability to activate CXCR3 until cleavage by a protease. Proteolytic cleavage of the CXCL peptides minimizes pro-inflammatory responses and inhibits fibrosis progression.

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.