44 results about "CCL19" patented technology

An object of the present invention is to provide CAR-expressing T cells that coexpress a chimeric antigen receptor (CAR) and a T cell immune function-enhancing factor and have a high immunity-inducing effect and antitumor activity, and to provide a CAR expression vector for the preparation of the CAR-expressing T cells.A CAR expression vector comprises a nucleic acid encoding a chimeric antigen receptor (CAR) and a nucleic acid encoding a T cell immune function-enhancing factor, wherein the nucleic acid encoding an immune function-enhancing factor is a nucleic acid encoding interleukin-7 and a nucleic acid encoding CCL19, a nucleic acid encoding a dominant negative mutant of SHP-1, or a nucleic acid encoding a dominant negative mutant of SHP-2, or a CAR-expressing T cell introduced with the CAR expression vector are prepared.

The invention provides construction and application of a fourth-generation chimeric antigen receptor T (CAR-T) cell (expressing IL-7 and CCL19) specific to Nectin-4 dual targets on the surface of a malignant tumor. Two spatial epitopes of a Nectin-4 antigen are taken as target points, and the constructed fourth-generation CAR-T is used for treating and expressing a malignant solid tumor of the Nectin-4 antigen to solve the immune escape problem of the CAR-T during treatment of the solid tumor; and the constructed fourth-generation CAR-T can enhance proliferative capacity and sustained survivability, so that the solid tumor is effectively treated, and a new strategy is provided for effective prevention and treatment of postoperative recurrence / metastasis of the solid tumor.

The invention relates to a preparation method of CAR (Cheimeric Antigen Receptors)-T cells for co-expressing IL18 (Interleukin 18) and CCL19 (Chemokine C-C motif ligand 19) protein and a targeting MUC1 gene. The preparation method comprises the following steps: transfecting DC<4+> / CD<+8> positive cells by lentivirus containing IL18 and CCL19 protein coding sequences and targeting MUC1 CAR; screening and culturing amplified and transfected T cells to obtain the CAR-T cells for co-expressing IL18 and CCL19 protein and the targeting MUC1 gene. According to the preparation method provided by the invention, the proliferation capability and the life cycle of the CAR-T cells are enhanced through expressing third cell signals IL18 and CCL19, improving the osmosis effect of the CAR-T cells in solidtumors and maintaining the killing effect of the CAR-T cells on the solid tumors. Furthermore, the co-expressed IL18 and CCL19 are connected through a 2A short peptide and can be expressed respectively.

The present invention discloses a chimeric antigen receptor using a CD99 receptor as a target site and a use of the chimeric antigen receptor. A splice peptide, a single-chain antibody ScFv, strepII,CD8 hinge, a CD28 transmembrane region, a CD28 intracellular structural domain, an intracellular co-stimulatory domain 4-1BB and a CD3-zeta chain are sequentially spliced from a N-terminus to a C-terminus, and more preferably, the splice signal peptide, the single-chain antibody ScFv, the strepII, the CD8 hinge, the CD28 transmembrane region, the CD28 intracellular structural domain, the intracellular co-stimulatory domain 4-1BB, the CD3-zeta chain, a F2A peptide, IL-7, a F2A peptide and CCL19 are sequentially spliced from the N-terminus to the C-terminus. The single chain antibody ScFv can specifically recognize the CD99 receptor on surfaces of tumor cells. The chimeric antigen receptor using the CD99 receptor as the target site is used to modify immune cells and the modified immune cellscan be used for treatment of surface CD99-positive tumors.

The purpose of the present invention is to provide, in order to continue the rejection of malignant tumors over a long period of time, an enhancer for endogenous T-cells or B-cells having a memory function, and a malignant tumor recurrence inhibitor. The present invention involves preparing: an enhancer for subject T-cells or B-cells having a memory function, said enhancer including a nucleic acidtransportation medium, a nucleic acid encoding interleukin 7 (IL-7) and a nucleic acid encoding chemokine (C-C motif) ligand 19 (CCL 19); an inducer which induces the memory function in the T-cells or B-cells in a subject; and a malignant tumor recurrence inhibitor which includes a nucleic acid transport medium, a nucleic acid encoding interleukin 7 (IL-7) and a nucleic acid encoding CCL19.

The purpose of this invention is to provide an immunocompetent cell that targets mesothelin. Another purpose is to produce 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). It is preferable that: the cell surface molecule that specifically recognizes human mesothelin is a chimera antigen receptor (CAR) provided with a single-chain antibody, a membrane-spanning domain and a signal transmission domain which induces the activation of the immunocompetent cell; and that the heavy chain variable domain and the light chain variable domain are linked via a peptide linker comprising a sequence of 2-30 amino acids.

The invention provides an expression vector for co-expressing secretory IL-7 and selective CCL19 and an application of the expression vector. The expression vector comprises an IL-6 signal peptide coding gene, an IL-7 coding gene, an NFAT regulatory promoter and a CCL19 coding gene. In the expression vector disclosed by the invention, the coding gene of IL-6 signal peptide is added to the upstreamof the IL-7 coding gene, so that secretory expression of the IL-7 by T cells is realized. The NFAT regulatory promoter is adopted as the promoter of the CCL19 coding gene, selective expression of theCCL19 by the T cells is realized, and the proliferation ability and tumor cell killing efficiency of CAR-T cells containing the expression vector are significantly improved.

The invention provides immunotherapy for targeted transportation of a chemotactic factor and a cytokine via a mesenchymal stem cell. Specifically, the invention provides the mesenchymal stem cell. Themesenchymal stem cell expresses an immunostimulatory factor, wherein the immunostimulatory factor is selected from the group consisting of CCL3, CCL19, CCL21, XCL1, CXCL9, OX40L, 4-1BBL, GITRL, CD40L, and combinations of the above immunostimulatory factors. The mesenchymal stem cell disclosed by the invention can specifically attract and activate immune cells for killing tumor tissues at a tumorpart, and the mesenchymal stem cell and chemotactic factor and / or cytokine have a synergistic effect, so the mesenchymal stem cell has an immune curative effect which is more efficient and low in sideeffect and is remarkably enhanced in tumor tissue killing capability, especially colorectal cancer cell killing capability.

It 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.

The invention discloses a novel model for prognosis prediction and diagnosis of colorectal cancer and application thereof, the model comprises immune related markers CCL11, CCL19, CCL22, CCL28, CXCR5, IDO1, LAG3, TIM4, HSPA1A, HSPA8, HSPA9, NOS2 and TGF beta1, the prognosis of a subject can be accurately predicted according to the model, the model provides a reliable prognosis prediction and diagnosis marker for evaluation of a patient with colorectal cancer, and the model can be applied to the prognosis prediction and diagnosis of the patient with colorectal cancer. The evaluation and prediction capability of prognosis prediction and diagnosis of the colorectal cancer patient is improved, and the application prospect in clinic is wide.

The invention discloses a hepatitis B immunotherapy agent targeting CCL19 / CCR7 and its use, and belongs to the technical field of biomedicine. The present invention provides a CCL19 protein with immune enhancing effect and a regulator AAV-shRNA-CCR7 (shCCR7) that knocks down the expression of its receptor CCR7 in promoting and increasing the ratio of CD8+ T cells and the activation and apoptosis of HBV antigen-specific T cells , applications in accelerating HBV clearance. It can be used to accelerate the clearance of HBV in mammals chronically infected with HBV, and provides a theoretical basis for the preparation of HBV preventive drugs or therapeutic vaccines.

An in vitro method of determining the type of a fibroepithelial tumour of the breast in a biological sample is provided. The method comprises the steps of obtaining an expression profile of one or more genes selected from the group consisting of PRAME, ADH1 B, CTHRC1, NPTX2, NEFL, ABCA8, DAPL1, TP63_v2, COL17A1, GCNT2, CCL19, MMP3, FN1, TRERF1, TRIM29, TESC, KIF20A, UHRF1, HEPACAM2, APOD, SERHL2. KIF15, HOXD13, GAGE2B, CALML5, C2orf40, ADH1C, CYP1B1, SPAG11B, GRB7, UBE2C, SYNGAP1, TP63_v1, LAMB1, OR5P3, SPC25, SHISA2, SCARA5, LHX2, RORC, DPYSL4, CH25H, and CHST1 in a sample and determining the differential activity of the one or more genes relative to a control; correlating the differential activity of the one or more genes relative to the control to obtain a p-score; and determining the type of fibroepithelial tumour based on the p-score, wherein a p-score of less than 0.5 is indicative of a fibroadenoma and a p-score of 0.5 and above is indicative of phyllodes tumour. Particularly, the said method is exemplified using an expression profile of five genes comprising of PRAME, FN1, CCL19, ABCA8 and APOD. A method for managing the treatment of a subject with a fibroepithelial tumour of the breast is also provided as well as a kit when used in the methods of the present invention.

The present invention discloses a chimeric antigen receptor using a CD99 receptor as a target site and a use of the chimeric antigen receptor. A splice peptide, a single-chain antibody ScFv, strepII,CD8 hinge, a CD28 transmembrane region, a CD28 intracellular structural domain, an intracellular co-stimulatory domain 4-1BB and a CD3-zeta chain are sequentially spliced from a N-terminus to a C-terminus, and more preferably, the splice signal peptide, the single-chain antibody ScFv, the strepII, the CD8 hinge, the CD28 transmembrane region, the CD28 intracellular structural domain, the intracellular co-stimulatory domain 4-1BB, the CD3-zeta chain, a F2A peptide, IL-7, a F2A peptide and CCL19 are sequentially spliced from the N-terminus to the C-terminus. The single chain antibody ScFv can specifically recognize the CD99 receptor on surfaces of tumor cells. The chimeric antigen receptor using the CD99 receptor as the target site is used to modify immune cells and the modified immune cellscan be used for treatment of surface CD99-positive tumors.

This application provides the construction and application of a fourth-generation chimeric antigen receptor T (CAR-T) cell (expressing IL-7 and CCL19) targeting Nectin-4 on the surface of malignant tumors. The present invention takes the two spatial epitopes of the Nectin-4 antigen as targets, and the fourth-generation CAR-T constructed is used to treat malignant solid tumors expressing the Nectin-4 antigen, so as to solve the immune problem of CAR-T in the treatment of solid tumors escape problem; and the construction of the fourth-generation CAR-T can enhance its proliferation ability and continuous survival ability, so as to effectively treat solid tumors, and provide a new strategy for the effective prevention and treatment of solid tumor recurrence / metastasis after surgery.