24 results about "CCL19" patented technology

The invention provides a novel marker for IgG4 related diseases and application of the novel marker, and particularly relates to application of OX40 serving as a biomarker to preparation of products for diagnosing IgG4-RD, evaluating disease activity of the IgG4-RD and evaluating recurrence risk prognosis of the IgG4-RD. On the basis of Olink proteomics analysis, expression of PD1, OX40, CCL19 and MMP12 in IgG4-RD patients is remarkably up-regulated, and the disease activity of the IgG4-RD patients is remarkably up-regulated. A verification queue verifies that the plurality of biomarkers have relatively high diagnosis efficiency, sensitivity and specificity, are in positive correlation with the IgG4 level, the inflammation index and the disease activity, and are in positive correlation with specific visceral organ enumeration. The invention finds that serum OX40 can be used as a baseline for predicting disease recurrence and evaluating a prediction index of recurrence risk.

The invention belongs to the technical field of biological medicine, and discloses a medicine for in-vivo engineering CAR-T and a preparation method thereof. The drug provided by the invention comprises a first RNA and a second RNA which are used for coding a chimeric antigen receptor in a specific molar ratio, the second RNA is used for coding at least two cytokines of CCL19, IL-17, IL-15, IL-2 or IL-24, by adopting the drug, the gene delivery efficiency and targeting of in-vivo engineered CAR-T can be improved, better T cell transformation and CAR + T cell generation effects are realized, the CAR-T cell depletion is reduced, and the drug has a good application prospect. According to the present invention, the CAR-T gene is constructed, such that the CAR-T gene can survive for a long time in the tumor microenvironment and continuously provide the treatment effect, has the excellent anti-tumor treatment effect, has the excellent application prospect in the in-vivo engineering CAR-T treatment, and has the important significance on the promotion of the efficient, safe and economical development of the CAR-T treatment.

The invention provides a method for evaluating effective cell functions in thymus tissue based on multi-factor combination, which comprises the following steps: detecting the content of molecular markers in thymus tissue slice culture supernatant, the molecular markers being one or a combination of more of IL16, L-Selectin, CCL19, CCL21, CXCL16 and CXCL12, and the content of the molecular markers being one or more of IL16, L-Selectin, CCL19, CCL21, CXCL16 and CXCL12. The combination of one or more of IL16 and L-Selectin is used for evaluating the effective cell function of the thymus tissue raw material, and the combination of one or more of CCL19, CCL21, CXCL16 and CXCL12 is used for evaluating the effective cell function of the thymus tissue slice finished product. The thymus tissue slice does not need to be lost, the consumed time is short, and the functions of effective cells in the thymus tissue slice can be accurately reflected.

The invention discloses a CAR (chimeric antigen receptor) recombinant lentiviral expression vector suitable for CIK (cytokine-induced killer) cells and NK (natural killer) cells to express EpCAM antibodies, IL-21 and CCL19, and belongs to the technical field of genetic engineering and biology. According to the expression vector, a CAR (chimeric antigen receptor) gene structure, an IL-21 (interleukin-21) gene expression structure and a CCL19 (chimeric antigen receptor 19) gene expression structure are connected between multiple cloning sites Nhe1 and Not1 of a vector pCHD-CMV-MCS-EF1-copGFP-T2A-puro, so that a recombinant plasmid pCDH-21 * 19 EpCAM-CAR is obtained. And transforming the recombinant plasmid into escherichia coli DH5alpha to obtain the recombinant microbial cell. The pCDH-21 * 19 EpCAM-CAR recombinant lentiviral expression vector is packaged, lentiviral particles are concentrated, CIK cells and NK cells are infected, and eukaryote transgenic cells are obtained. The CAR vector aiming at the solid tumor colorectal cancer is constructed, the design of the vector aims at improving the activating and killing capacity of CIK cells and NK cells and solving the problems of tumor microenvironment immunosuppression and the like, and a foundation is further laid for the research of treating solid tumors by applying a CAR technology.

The present application relates to immunocompetent cells and expression vectors expressing immune function regulatory factors. The subject of the present invention is to provide immunocompetent cells expressing immune function regulatory factors of immunocompetent cells and having both proliferation ability, survival ability, and T cell aggregation ability, and to provide immunocompetent cells for preparing the immune function regulatory factor expression vectors of the immunocompetent cells. Prepare immunocompetent cells expressing cell surface molecules that specifically recognize cancer antigens, interleukin 7 (IL-7), and CCL19. The cell surface molecules that specifically recognize cancer antigens are preferably T cell receptors that specifically recognize cancer antigens, and the immunocompetent cells are preferably T cells.

An object according to certain aspect(s) of the present invention is to provide an immunocompetent cell that expresses regulatory factors of immunocompetent cell immune function and possesses all of proliferative potential, viability, and the ability to accumulate a T cell, and an expression vector of regulatory factors of immune function for generating the immunocompetent cell. An immunocompetent cell expressing a cell surface molecule specifically recognizing a cancer antigen, interleukin 7 (IL-7), and CCL19 is generated. Preferably, the cell surface molecule specifically recognizing a cancer antigen is T cell receptor specifically recognizing the cancer antigen, and the immunocompetent cell is a T cell. Another object according to certain aspect(s) of the present invention is to provide an immunocompetent cell targeting mesothelin. An immunocompetent cell that expresses a cell surface molecule specifically recognizing human mesothelin, interleukin 7 (IL-7), and chemokine (C-C motif) ligand 19 (CCL19) is produced. It is preferred that: the cell surface molecule specifically recognizing human mesothelin should be chimeric antigen receptor (CAR) having single chain antibody, a transmembrane region, and a signaling region that induces the activation of the immunocompetent cell; and the heavy chain variable region and the light chain variable region should be connected via a peptide linker consisting of a 2- to 30-amino acid sequence.

The invention discloses an application of an FHL2-L4 peptide fragment in preparation of a medicine for treating atherosclerosis. The invention particularly relates to an application of an FHL2-L4 peptide fragment, an fhl-l4 gene, an expression cassette, a recombinant vector, a recombinant cell or recombinant bacteria, an overexpression vector, sgRNA, a gene knockout vector and a correspondingly packaged virus in preparation of medicines for treating atherosclerosis. It is found for the first time that the L4 peptide fragment serves as the minimum functional unit for promoting atherosclerosis of FHL2, plaque formation can be remarkably inhibited through specific knockout of the L4 peptide fragment, and the effect is directly related to CCL19 / 21 signal channel inhibition. Based on this, gene editing or antagonistic peptide design of targeting L4 can be used as a breakthrough strategy for atherosclerosis treatment.

Provided is a composition for inhibiting fibrosis of the intestinal tract, said composition comprising, as an active ingredient, a molecule that inhibits the function of the CCL19 gene.

A composition for preventing or treating cancer or infectious disease is disclosed. The composition contains, as an active ingredient, a pluripotent stem cell-derived immune cell expressing IL-7, CCL19, or a combination thereof. The composition provides a multifaceted and synergistic therapeutic effect derived from the complementary immune response of the patient's endogenous T cells and the injected natural killer cells, by administering only a therapeutically effective amount of immune cells other than T cells, specifically natural killer cells. The natural killer cells of the composition may also be co-administered with exogenous T cells to allow these different cell populations to act more intensively at the lesion site. The composition is based on the differentiation of pluripotent stem cells, specifically induced pluripotent stem cells (iPSCs) into immune cells, thus can be used to generate an unlimited supply of allogenic or autologous cells as needed.

This application relates to enhancers of T cells or B cells with memory function, inhibitors of malignant tumor recurrence, and inducers of memory function in T cells or B cells. The object of this invention is to provide enhancers of endogenous T cells or B cells with memory function and inhibitors of malignant tumor recurrence for long-term, sustained rejection of malignant tumors. Enhancers of T cells or B cells with memory function in the recipient, and inducers of memory function in T cells or B cells in the recipient, are prepared, wherein the enhancers and inducers comprise a nucleic acid delivery medium, a nucleic acid encoding interleukin-7 (IL-7), and a nucleic acid encoding chemokine (C-C motif) ligand 19 (CCL19). Additionally, an inhibitor of malignant tumor recurrence is prepared, comprising a nucleic acid delivery medium, a nucleic acid encoding interleukin-7 (IL-7), and a nucleic acid encoding CCL19.

The application discloses a detection method of a triple negative breast cancer immunotherapy efficacy prediction marker CCL19. The application provides application of CCL19 as a marker in preparation of a breast cancer immunotherapy efficacy and / or prognosis prediction product. A triple negative breast cancer immunotherapy efficacy and prognosis prediction kit comprising a CCL19 protein detection reagent and optionally an instruction is also provided. Application of a CCL19 molecule in combination with a second therapeutic agent in preparation of an antitumor drug is also provided. The application greatly fills the vacancy of triple negative breast cancer immunotherapy efficacy prediction liquid biopsy, and realizes precise prediction of immunotherapy efficacy in a noninvasive, rapid and low-cost manner.

To provide an enhancer of endogenous T-cells or B cells having a memory function and an inhibitor of malignant tumor recurrence that continue rejecting malignant tumors for a long period of time.SOLUTION: An enhancer of T-cells and B-cells having a memory function in an administration target comprising a nucleic acid delivery vehicle, a nucleic acid encoding interleukin 7 (IL-7) and a nucleic acid encoding chemokine (C-C motif) ligand 19 (CCL19) or an inducer that induces memory function in T-cells and B-cells in an administration target is prepared. Also, an inhibitor of malignant tumor recurrence containing a nucleic acid delivery vehicle, a nucleic acid encoding interleukin 7 (IL-7) and a nucleic acid encoding CCL19 is prepared.SELECTED DRAWING: Figure 10

The invention discloses a group of serum protein markers for identifying systemic lupus erythematosus. The serum protein markers comprise MCP-3, ST1A1, TNF, TGF-alpha, CSF-1, AXIN1, CXCL9, IL-15RA, IL18, CCL3, IL10, 4E-BP1, PD-L1, SIRT2, CCL11, CDCP1, IL-18R1, FGF-23, CD40, STAMBP, IL6, IL-17C, CD8A, CXCL10, CXCL5, DNER, FGF-19, LAP TGF-beta-1, CCL28, CASP-8, IL8, CCL23, CCL20, CCL19, MCP-1, VEGFA, uPA, OPG, OSM, various novel protein markers which are expected to be used for screening and identifying systemic lupus erythematosus are identified.

The present invention provides a novel biomarker for IgG4-related diseases and its applications, specifically the application of OX40 as a biomarker in the preparation of products for diagnosing IgG4-RD, evaluating the disease activity of IgG4-RD, and prognosticating the recurrence risk of IgG4-RD. Based on Olink proteomic analysis, the present invention found that the expressions of PD1, OX40, CCL19, and MMP12 were significantly upregulated in patients with IgG4-RD. After verification in a validation cohort, these biomarkers have high diagnostic efficacy, sensitivity, and specificity, are positively correlated with IgG4 levels, inflammatory indicators, and disease activity, and are related to specific organ involvement. The present invention found that serum OX40 can be used as a predictive indicator for baseline prediction of disease recurrence and evaluation of recurrence risk.

The invention belongs to the technical field of biomedicine, and relates to an exosome vaccine as well as a preparation method and application thereof, and the exosome vaccine is an exosome which expresses coexistence of CCL19 full-length CDS and neoantigen through lentivirus construction by utilizing HEK-293 FT cells. According to the exosome vaccine, antigen presenting cells are targeted in a CCL19-CCR7 receptor-ligand mediated targeted delivery mode, the antigen presenting cell uptake and delivery efficiency of the Neo-CCL19Exos vaccine is improved, MHC-I dependent antigen cross presentation is efficiently activated, TLS formation in liver cancer is promoted, liver cancer is induced to be converted from cold tumor to hot tumor, and liver cancer is induced to be cured. Therefore, a novel method is provided for designing vaccines and enhancing the immune curative effects of the vaccines in the future.

The invention relates to a T cell for expressing CAR and a CAR expression vector. Provided is an immune cell (CAR-T cell or the like) having higher antitumor activity than an immune cell (CAR-T cell or the like) that expresses CAR alone (not expressing a cytokine and / or a chemokine). A T cell provided in one aspect of the invention expresses (1) a chimeric antigen receptor (CAR), (2) at least one selected from the group consisting of interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21), and interleukin-27 (IL-27), and (3) a CC chemokine ligand 19 (CCL19).

An anticancer agent for solid cancer, which contains, as an active ingredient, human parainfluenza virus type 2 that expresses at least one cytokine selected from the group consisting of IL-2, IL-7, IL-12, IL-15 and IL-18, or a combination of said cytokine with CCL19 and / or CCL21, or a mutant thereof having the same function.

The present invention provides a pluripotent stem cell expressing the following (a) and (b):(a) an exogenous gene encoding CC chemokine receptor 2 type B(CCR2B)(b) an exogenous gene encoding CC chemokine ligand 19 (CCL19), or an NK cell derived from the pluripotent stem cell or a progenitor cell thereof.

The invention provides an application of HY-133073 in preparation of a medicine for resisting immune escape of liver cancer center. Based on a tumor immune escape mechanism related to thymus in a liver cancer morbidity process found for the first time, the tumor immune escape mechanism is named as tumor central immune escape, the invention specifically discloses application of HY-133073 in preparation of drugs for resisting liver cancer central immune escape, and the main mechanism is that HY-133073 inhibits signal transduction after CCR7 is combined with CCL19 or CCL21, and the HY-133073 inhibits signal transduction after CCR7 is combined with CCL19 or CCL21. Therefore, CCR7 positive CD8 T cells are inhibited from homing to thymus and immune escape to the center, infiltration of the CD8 T cells to liver tumors is enhanced, and the anti-cancer effect is achieved. The compound can be used for preparing liver cancer central immune escape inhibition drugs or central immune escape inhibition drugs for liver cancer treatment and tumor immune research.

The present invention provides immune cells (CAR-T cells, etc.) having higher anti-tumor activity than immune cells (CAR-T cells, etc.) expressing CAR alone (not expressing cytokines and / or chemokines). One aspect of the present invention provides T cells expressing (1) a chimeric antigen receptor (CAR), (2) at least one selected from the group consisting of interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21) and interleukin-27 (IL-27), and (3) CC chemokine ligand 19 (CCL19).

The invention belongs to the technical field of biological medicines, and particularly discloses a CCR7 affinity peptide, a coding nucleic acid and application of the CCR7 affinity peptide. According to the invention, CCR7 is taken as a target molecule, and the CCR7 affinity peptide CRBP3 is obtained through a phage display dodecapeptide library high-throughput screening technology. In-vitro function experiments show that the CRBP3 can efficiently target CCR7 + DC, promote phagocytosis of CCR7 + DC on antigens, stimulate T cell proliferation and enhance T cell functions, and the CRBP3 does not block a CCR7-CCL19 / CCL21 pathway and does not inhibit migration of CCR7 + DC. In-vivo anti-tumor experiments show that the CCR7 affinity peptide coupled polypeptide vaccine can improve presentation of antigens, initiate powerful specific CD8 + T cellular immune response and remarkably inhibit growth of tumors, has the effects of inhibiting tumor recurrence for a long time and establishing immune memory, and can provide new effective treatment strategies and candidates for improving the anti-tumor effect.

The present invention relates to in situ recruitment, reprogramming and release of CAR-T cells. The present invention discloses a hydrogel matrix comprising one or more chemical attractants wherein the one or more chemical attractants comprise a C-C motif chemokine ligand (CCL) 1 (CCL1), a CCL5, a CCL19, a CCL21, a CCL22, a CCL28, a C-X-C motif chemokine ligand (CXCL) 1 (CXCL1), CXCL9, CXCL10, CXCL11, CXCL12, M-CSF, GM-CSF, MCP-1, MCP-3, CCL2, CCL3, CCL7, CCL20, CX3CL1, BRAK, IL-12, S1P, and / or MCP2. Also disclosed are a method of treating cancer in a subject and a method of transferring immune cells in a subject.

The invention belongs to the biomedical technology, and particularly relates to a chimeric antigen receptor targeting HCC cells and application thereof, the chimeric antigen receptor comprises an extracellular domain, a transmembrane domain (TM) and an intracellular signal domain, and is characterized in that the extracellular domain comprises a GPC3 antigen binding domain, and the intracellular signal domain comprises a cytokine IL-7 and a chemotactic factor CCL19. Tumor antigen phosphatidylinositol proteoglycan 3 (GPC3) highly expressed on the surface of an HCC cell is selected as a main target spot of hepatocellular carcinoma CAR-T treatment, a second-generation GPC3-CAR-T cell is constructed, a transgenic cell factor IL-7 and a chemotactic factor CCL19 are increased to enter the CAR-T cell, and the cell factor IL-7 and the chemotactic factor have the effects of starting cell system immunity, promoting cell apoptosis, promoting cell apoptosis and the like. NK cells and cytotoxic T cells are gathered to a solid tumor area, and the problem that CAR-T cells are immersed into solid tumors is solved.