460 results about "CD19" patented technology

Various embodiments of the invention provide binding molecules for B-lymphocyte antigen (e.g., CD 19 and CD20), including antigen recognizing receptors (e.g., CARs) that target B-lymphocyte antigens (e.g., CD 19 and CD20). Embodiments of the invention also provide cells expressing such binding molecules, therapeutics compositions comprising such cells, and methods for treating diseases or disorders associated with B-lymphocyte antigen (e.g., CD19 and CD20), including a hematologic cancer, an autoimmune disease (e.g., multiple sclerosis and systemic lupus erythematosus).

The invention belongs to the technical field of stem cells, and particularly relates to a product containing mesenchymal stem cells, a preparation method, a quality control method and application in prevention and treatment of digestive system diseases. According to the preparation method, 1-3 complete culture media are provided for culturing the mesenchymal stem cells, and the obtained mesenchymal stem cells are good in subpackage form; cD73, CD90 and CD105 are highly expressed, and CD19, CD34, CD45, CD11b and HLA-DR are not expressed; the cell proliferation capacity is strong, the osteogenesis and adipogenic differentiation capacity is strong, and the medicine is safe and free of toxic and side effects. The prepared mesenchymal stem cells are high in quality, have good performance of secreting HGF, KGF and IGF-1, and can effectively treat digestive system diseases.

The invention provides an antibody for resisting CD19 on the surface of a porcine B cell or an antigen binding fragment thereof as well as a composition and application thereof. Specifically, the invention provides an anti-porcine B cell surface CD19 antibody or an antigen binding fragment thereof, which can effectively bind to CD19 on the porcine B cell surface. The invention also provides an antibody drug conjugate containing the antibody or the antigen binding fragment thereof, and the antibody drug conjugate can be applied to screening of porcine B cells and marking of CD19 antigens on the surfaces of the porcine B cells, and has a good application prospect.

The invention includes improved methods and compositions for detecting specific insertion of a chimeric antigen receptor (CAR) sequence in the desired locus in the genome of a cell. Methods are useful as quality control for CAR-T cell or CAR-NK cell preparations.

The invention provides a preparation method of a PSR.Syn.CD19. BCMA CAR-T cell as well as the cell and application of the PSR.Syn.CD19. BCMA CAR-T cell, the PSR.Syn.CD19. BCMA CAR-T cell is characterized in that after the CAR-T cell and a CD19 antigen positive tumor cell are co-incubated, the expression of an effector molecule BCMA-CAR can be induced, and if the tumor cell simultaneously expresses a BCMA antigen, the CAR-T cell capable of killing a tumor can be identified. Experimental results show that the cell prepared by the method can efficiently and specifically kill tumor cells, has a persistent killing effect and has a safety switch capable of starting a killing function. In addition, the tumor can be specifically killed, the cell proliferation rate is high, and the proliferation rate under the stimulation of tumor cells is higher than that of a PAN-T group.

The use of dual-target CAR-T cells in treating systemic lupus erythematosus and other B-cell autoimmune diseases is provided. The first target of the chimeric antigen receptor is CD19, the second target is BCMA, and specifically, the chimeric antigen receptor is a chimeric antigen receptor with a Loop structure, which is shown as follow: L-VL, CD19-VH, BCMA-VL, BCMA-VH, CD19-H-TM-C-CD3ζ; the BCMA-CD19 CAR-T cells transduced by the chimeric antigen receptor targeting CD19 and BCMA can completely block the pathway of producing autoantibodies, and completely cover the B cells, plasmablasts and plasma cells at multiple differentiation stages that produce autoantibodies, so that the dual-target CAR-T therapy designed based on this concept can be aimed at refractory SLE and is expected to achieve faster remission and deeper and lasting curative effect.

A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Provided herein are bispecific antibodies having modifications that enable greater developability and manufacturability. In certain instances, such bispecific antibodies comprise common light chain bispecific antibodies that bind CD38 and CD19, having reduced isoelectric focusing, improved hydrophobic interaction chromatography retention, and effective targeting of cells expressing CD19 and CD38. Also provided are methods of reducing an experimental isoelectric point of bispecific antibodies that bind CD19 and CD38.

A CD20-OR-CD19 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD20-OR-CD19 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD20-OR-CD19 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

The present disclosure provides bispecific chimeric antigen receptors that target BCMA and CD19. The CAR may comprise an scFv targeting BCMA and an scFv targeting CD19, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasm signaling domain. Chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

The invention relates to a method for detecting a B cell subset in a lymphatic tissue, a kit comprising a quantum dot-antibody CD19 conjugate, a quantum dot-antibody CD138 conjugate and a quantum dot-antibody CD1d conjugate is used for dyeing a lymphatic tissue section, and different antibodies are marked by quantum dots with different colors, so that the B cell subset in the lymphatic tissue section can be detected, and the B cell subset in the lymphatic tissue section can be detected. Content and positions of plasma cells and regulating B cells are confirmed, so that biological behaviors of the plasma cells and regulating B cells can be determined conveniently. According to the method, the existing multi-color immunofluorescence technology is improved, a secondary antibody dyeing link is omitted by using a quantum dot carrying antibody method, a direct method is adopted for marking, the advantages of quantum dots are exerted, the experiment time is saved, and the efficiency is improved.

The invention discloses a kit and method for detecting leukemia and lymphoma based on full-spectrum flow cytometry, the kit comprises 25 antibodies, the antibodies are specifically bound with fluorescein respectively, and leukemia and lymphoma are detected through full-spectrum flow cytometry; the 25 kinds of antibodies comprise HLA-DR (human leukocyte antigen-DR), CD38, CD7, CD34, Lambda, CD19, CD64, CD14, CD5, CD123, CD16, CD20, Kappa, CD117, CD13, CD45, CD11b, CD2, CD10, CD8, CD15, CD4, CD3, CD56 and CD33. The kit comprehensively covers development stages of various lines of bone marrow cells, and common abnormal expressions of various leukemia, myelodysplastic syndromes and lymphoma, and can preliminarily screen various leukemia and lymphoma.

A bispecific or dual target CAR or CAR-T cells can be used to treat and / or prevent an autoimmune disease. The bispecific CAR may target CD19 and BCMA. The CAR may have a loop structure, which is shown as follow: L-VL, CD19-VH, BCMA-VL, BCMA-VH, CD19-H-TM-C-CD3ζ; the BCMA-CD19 CAR-T cells transduced by the chimeric antigen receptor targeting CD19 and BCMA can completely block the pathway of producing autoantibodies, and completely cover the B cells, plasmablasts and plasma cells at multiple differentiation stages that produce autoantibodies, so that the dual-target CAR-T therapy designed based on this concept can be aimed at refractory SLE and is expected to achieve faster remission and deeper and lasting curative effect.

Provided herein are methods and compositions for treating a subject having an autoimmune disorder, such as multiple sclerosis, autoimmune encephalitis, Sjogren's syndrome, kidney transplantation, IgG4-related disease, ANCA-associated vasculitis, chronic inflammatory demyelinating polyradiculoneuropathy, neuromyelitis optica spectrum disorder, and idiopathic inflammatory myopathy (e.g., antisynthetase syndrome, dermatomyositis, immune-mediated necrotizing myopathy, or polymyositis), using T cells engineered with a chimeric antigen receptor that binds CD19.

The invention relates to a CD19 antibody pharmaceutical preparation. Specifically, the invention relates to the pharmaceutical preparation of the irnerizumab, and the pharmaceutical preparation comprises the irnerizumab, a buffer solution, a stabilizer and a surfactant. The pharmaceutical preparation can prevent aggregation, degradation, oxidation or denaturation and the like of the irnerizumab, so that the biological activity of the effective components of the irnerizumab is maintained, and the pharmaceutical preparation is suitable for clinical use.

The invention discloses an E-CAR-NK cell for treating systemic lupus erythematosus and application of the E-CAR-NK cell, and belongs to the technical field of genetic engineering.A CD19 and BCMA double-target E-CAR is adopted for modifying an NK cell, and the E-CAR-NK cell is obtained; the CD19 and BCMA double-target E-CAR is composed of the following modules: a CD8 signal peptide, a CD19 scFv, a Linker, a BCMA scFv, a CD8 Hinge region, an NKG2D transmembrane region, a CD3 epsilon signal transduction region, a DAP12 costimulatory region, a 2B4 costimulatory region, and a CD3 zeta signal transduction region. Compared with a common CAR-NK cell, the E-CAR-NK cell disclosed by the invention has higher antigen sensitivity and better continuous killing ability, so that the treatment effect of SLE is improved, and the E-CAR-NK cell has lower side effects and higher safety.

The present invention generally relates to antibodies that bind to CD3 and CD19, e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease.

The invention provides a preparation method of a PSR.Syn.CD19. CD38 CAR-T cell as well as the cell and application of the PSR.Syn.CD19. CD38 CAR-T cell, the PSR.Syn.CD19. CD38 CAR-T cell is characterized in that after the CAR-T cell and a CD19 antigen positive tumor cell are co-incubated, effector molecule anti-CD38-CAR can be induced to express, and when the tumor cell simultaneously expresses CD19 and CD38 antigens, the CAR-T cell capable of recognizing and killing tumors can be identified. The CAR-T cell provided by the invention can efficiently and specifically kill tumor cells (CD19 + CD38 +), has a persistent killing effect, and has a safety switch capable of starting a killing function. Besides, the tumor can be specifically killed, the cell proliferation rate is high, the anti-tumor function can be improved through a large amount of secreted IL-2, IFN-gamma, TNF-alpha and Granzyme B, and the application safety of the cell is greatly improved.

Disclosed herein are antibodies or antigen-binding fragments thereof that specifically bind to human CD19. Chimeric antigen receptors and chimeric antigen receptor transgenes comprising an antigen binding domain that specifically binds to human CD19 are also disclosed. Also described herein are immune cells, viral vectors, and other compositions containing the antibodies, the antigen binding fragments, the chimeric antigen receptors, and / or the chimeric antigen receptor transgenes.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

Provided are multispecific antigen binding proteins (MSAPs), such as trispecific antigen binding proteins (TSAPs or trispecific T cell engagers), that specifically bind to CD20, CD19, and CD3. Also provided are TSAPs or bispecific antigen binding proteins (BSAPs), that specifically bind to CD3 and CD20. Compositions (e.g., pharmaceutical compositions), kits, methods of use (e.g., treating cancer), and methods of making thereof are also provided.

The invention relates to the field of biotechnology and cell therapy, in particular to a recombinant construct, a CAR (chimeric antigen receptor) modified cell and application. On the objective basis of different antigen target spots, such as CD19, CLDN18.2 or BCMA and other different antigen target spots corresponding to abnormal expression of tumors, the target spots are used as target spots for clinical treatment; under the condition that the expression of the chimeric antigen is not changed, two cell factors are secreted synergistically; the long-term treatment effect of immune cells is enhanced, and meanwhile, the treatment risk is reduced.

The invention belongs to the field of immune cell therapy, and particularly relates to application of a double-target CAR-T cell to treatment of systemic lupus erythematosus and other B-cell autoimmune diseases. A first target point of the chimeric antigen receptor is CD19, a second target point of the chimeric antigen receptor is BCMA, and the chimeric antigen receptor with the Loop structure is specifically the chimeric antigen receptor with the Loop structure, and the structure of the chimeric antigen receptor with the Loop structure is shown as follows: L-VL, CD19-VH, BCMA-VL, BCMA-VH and CD19-H-TM-C-CD3zeta; the BCMA-CD19 CAR-T cell transduced by the chimeric antigen receptor can more comprehensively block the way of generating the autoantibody in the process of targeting CD19 and BCMA, and can more completely cover B cells, plasma mother cells and plasma cells which generate the autoantibody and are in a plurality of differentiation stages; therefore, the double-target CAR-T therapy designed on the basis of the concept can be used for treating refractory SLE, and is expected to obtain quicker relieving and deeper and lasting curative effects.

The present disclosure relates to BCMA / CD19 CAR T-cell products and methods for treating relapsed or refractory BCMA+ or CD19+ malignancies.

The invention provides a preparation method of a Syn-CAR-T cell, the Syn-CAR-T cell and application of the Syn-CAR-T cell, and the method comprises the following steps: constructing a stably transfected SIN-gamma-RV vector, namely a PSR vector, by using a PiggyBac transposon system, preparing a Syn CAR plasmid vector, expressing a SynNotch system by using the PSR vector, combining a GAL4 induction vector and a UAS effect vector of the SynNotch system on the PSR vector, and preparing the Syn CAR plasmid vector. Enabling the SynNotch system to be delivered by one PSR vector, and constructing a plasmid of the Syn CAR retrovirus vector; and the plasmid of the retroviral vector is used for transduction of a T cell, and the Syn-CAR-T cell is prepared. Results of the invention show that the induction efficiency of the target spots BCMA, CD38 and GPC3 is extremely low, and the target spots are not suitable for the SynNotch system of the invention; the induction efficiency of the target CD19 is highest, and the target CD19 is most suitable for being applied to the SynNotch system.

The invention provides a new bunyavirus neutralizing antibody screening method based on single cell BCR sequencing. The new bunyavirus neutralizing antibody screening method comprises the following steps: S1, collecting peripheral blood B cells of acute stage and recovery stage patients and healthy volunteers of new bunyavirus infected persons; s2, carrying out CD19 < + > CD38 < + > CD138 < + > magnetic bead separation to obtain a single-cell suspension; s3, constructing a single cell transcriptome and a BCR library, separating single cells by using a microfluidic system, and performing high-throughput sequencing; s4, analyzing a B cell subset, a BCR cloning amplification mode and a VJ gene pair enrichment characteristic through bioinformatics analysis; and S5, screening a specific BCR clone type related to the severity of the disease as a neutralizing antibody candidate target. The method provided by the invention provides powerful support for immune monitoring and vaccine design of new bunyavirus infection, and is expected to provide new strategies and methods for clinical treatment and prevention.

The invention relates to an antibody composition, a kit and a system for rapidly screening acute promyelocytic leukemia. The antibody composition comprises a first group of antibodies, a second group of antibodies and a third group of antibodies, the first group of antibodies comprises a CD71 antibody, a CD33 antibody, a CD117 antibody, a CD34 antibody, an HLA-DR antibody, a CD19 antibody, a CD10 antibody, a CD7 antibody and a CD45 antibody; the second group of antibodies comprises a CD38 antibody, a CD56 antibody, a CD16 antibody, a CD34 antibody, a CD13 antibody, a CD11b antibody, a CD64 antibody, a CD15 antibody and a CD45 antibody; the third group of antibodies comprises a CD9 antibody, an MPO antibody, a CD117 antibody and a CD45 antibody; and each antibody is a monoclonal antibody marked with a detection marker. The antibody composition comprises a CD117 + CD33 + region as a main target cell population, and covers three groups of antibodies for identifying acute promyelocytic leukemia, such as CD33, CD34, CD64, CD13, CD9 and MPO, the acute promyelocytic leukemia can be rapidly, simply and conveniently detected by adopting the antibody composition, the detection sensitivity is high, the specificity is high, the accuracy rate is high, and the antibody composition can be widely applied to detection of acute promyelocytic leukemia. The acute promyelocytic leukemia patient can be accurately and quickly identified, and early diagnosis and early treatment are realized.