383 results about "Plasma cell" patented technology

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.

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.

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.

To provide a phagocytotic promotor of macrophage by a lactic acid bacterium, an activator of a plasmacytoid dendritic cell (pDC) by a lactic acid bacterium, and an activator of a myeloid dendritic cell (mDC) by a lactic acid bacterium.SOLUTION: A phagocytotic promotor of macrophage, an activator of a plasmacytoid dendritic cell (pDC), an activator of a myeloid dendritic cell (mDC) can be provided by including Lactobacillus panisapium M1 strain (NITE BP-03106) as an active ingredient.SELECTED DRAWING: None

The invention discloses a neutralizing nucleic acid aptamer for targeted inhibition of a B cell activating factor and application of the neutralizing nucleic acid aptamer in treatment of systemic lupus erythematosus. The neutralizing aptamer disclosed by the invention can be used for efficiently inhibiting the combination of BAFF and specific receptors on a B cell membrane, including a BAFF receptor (BAFF-R), a human calcium regulatory cyclophilin ligand interaction molecule (TACI) and a B cell maturation antigen (BCMA), so that the proportion of plasma cells, plasma mother cells and hair growth center B cells is reduced, and finally, the generation and secretion of autoantibodies are reduced; the compound has a targeted therapeutic effect on systemic lupus erythematosus. Compared with an existing biological agent for neutralizing BAFF, the neutralizing nucleic acid aptamer has the advantages of being high in specificity, high in affinity, easy to synthesize, low in immunogenicity, low in cost, capable of being designed and programmed and the like, is a potential novel nucleic acid preparation for SLE targeted therapy, and has a good clinical transformation application prospect.

To provide an oral composition for effectively activating plasmacytoid dendritic cells (pDCs).SOLUTION: An oral composition for activating plasmacytoid dendritic cells (pDCs), comprising Lacticaseibacillus rhamnosus CRL1505, wherein the composition is preferably intended for immune activation. The oral composition for activating pDCs is considered to: regulate both innate immunity and acquired immunity; act on an overall immune function, maintain a normal immune function, and maintain good physical conditions. The present invention also provides an oral composition for immune activation characterised in that it comprises Lacticaseibacillus rhamnosus CRL1505, wherein the immune activation is intended for symptoms such as nasal congestion.SELECTED DRAWING: Figure 1

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. Some methods, such as when a subject has preexisting against an immunogen to be administered, use plasma cell depleting agents or combinations comprising plasma cell depleting agents to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting. Other methods, such as when a subject has no preexisting immunity against an immunogen to be administered, use B cell depleting agents (e.g., anti-CD20xCD3 antibody or functional fragment thereof) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

The invention relates to a therapeutic drug, in particular to a construction method and application of a cell factor sustained-release complex combined with stem cells, and the cell factor sustained-release complex can be used for preventing intrauterine adhesion and promoting endometrial repair. The invention aims to provide a construction method and application of a cell factor slow-release complex combined with stem cells, so that the cell factor slow-release complex is effectively applied to repair of intrauterine adhesion and endometrium. According to the technical scheme, the construction method of the cell factor slow-release complex combined with the stem cells comprises the following steps: (1) preparing platelet-rich plasma, activating and enriching platelet-rich plasma cell factors, and adsorbing the released cell factors through hydrogel; (2) preparing a vascular extracellular matrix by using a decellularization technology, wherein the vascular extracellular matrix is used for adsorbing platelet-rich plasma cytokines; (3) acquiring umbilical cord mesenchymal stem cells; constructing an umbilical cord mesenchymal stem cell / extracellular matrix slow-release complex; and (4) preparing the cell factor slow-release complex combined with the stem cells.

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 invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The present invention relates to engineered plasmacytoid dendritic cell (pDC) expressing synthetic receptors that recognise Trop2 on a target cell, and their use in methods for treating cancer.

Provided are a fully human TSH receptor (TSHR) blocking monoclonal antibody for treating hyperthyroidism, and a preparation method therefor and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and memory single B cells specifically recognizing a TSHR in the peripheral blood of patients having high titers of TSHR blocking antibody (TSH-stimulating blocking antibody, TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells for antibody property screening and validation, to obtain a blocking monoclonal antibody specifically targeting human TSHR. The fully human TSHR blocking monoclonal antibody can specifically bind to the TSHR, has good inhibitory activity in vitro and in vivo experiments, and has broad application prospects in the development of treatment of Graves' diseases.

Antibodies and antibody fragments that bind to BDCA2 are disclosed. Also disclosed are methods of using the antibodies and antibody fragments to induce death of a plasmacytoid dendritic cell, inhibit production or secretion of inflammatory cytokines and chemokines, and treat or prevent immunological disorders such as inflammatory and autoimmune conditions.

The invention discloses a group of blocking monoclonal antibodies of an SH1 homologous cluster fully human thyrotropin receptor (TSHR) (a TSH receptor, TSHR) as well as a preparation method and application of the blocking monoclonal antibodies of the SH1 homologous cluster fully human thyrotropin receptor (TSHR). The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH receptor blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; expression and fibrosis of effector cell orbital fibroblasts TSHR for inhibiting thyroid-related eye diseases are remarkably relieved, and wide application prospects are achieved in treatment of Graves' diseases and diseases such as thyroid eye diseases caused by hyperthyroidism.

Methods are described herein for screening an antibody producing cell within a microfluidic environment. The antibody producing cell may be a B cell lymphocyte, which may be a memory B cell or a plasma cell. An antigen of interest may be brought into proximity with the antibody producing cell and binding of the antigen by an antibody produced by the antibody producing cell may be monitored. Methods of obtaining a sequencing library from an antibody producing cell are also described.

The invention discloses a group of blocking monoclonal antibodies of a CHK36 homologous cluster fully human TSH receptor (TSHR) as well as a preparation method and application of the blocking monoclonal antibodies. The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH-blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells, so as to obtain the TSHR-TBAb-TSHR-TBAb. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; according to the present invention, with the application of the compound, the expression and the fibrosis of the effector cell orbit fibroblast TSHR inhibiting the thyroid-related eye disease can be significantly reduced, and the wide application prospect is provided in the treatment of Graves' disease (Graves' disease, GD) and diseases caused by hyperthyroidism, such as thyroid eye disease (thyroid eye disease, TED), and the like.

To provide recombinant polyclonal proteins and use methods thereof.SOLUTION: Provided herein is a composition comprising recombinant polyclonal proteins (RPPs) derived from mammalian plasma cells or plasmablasts. Methods for using the RPPs are also provided. The RPPs are recombinant, and their sequences are derived from peripheral blood plasma cells or plasmablasts. The peripheral blood plasma cells or plasmablasts are mobilized by, e.g., a vaccine administered to a donor, and the peripheral blood plasma cells or plasmablasts are specifically separated from other peripheral blood cells. The peripheral blood cells can come from any mammal, for example a mouse, a rat, a human, a monkey, a horse, or a cow.SELECTED DRAWING: None

This disclosure features methods to treat viral diseases and / or hypercytokinemia using compounds that disrupt the tricarboxylic acid (TCA) cycle and / or compounds that activate the unfolded protein response (UPR) in immune cells such as plasmacytoid dendritic cells. In some embodiments, the immune cells are dendritic cells, macrophages, T cells, B cells, natural killer cells, and / or neutrophils.

The invention relates to a kit for detecting plasma cells and related antibody levels in a thymus microenvironment and application of the kit. The kit comprises a quantum dot labeled antibody CD138, a quantum dot labeled antibody CD21, a quantum dot labeled AchR, Musk and / or LRP4 receptor, an antigen repair solution and a DNA fluorescent dye solution, wherein the quantum dot labeled antibody CD138, the quantum dot labeled antibody CD21, the quantum dot labeled AchR, the quantum dot labeled Musk and / or the quantum dot labeled LRP4 receptor, the antigen repair solution and the DNA fluorescent dye solution; through the kit, one or more of plasma cells, follicular DC and related antibodies in a thymus (tumor) sample can be detected, so that the immune level of a tissue slice sample is obtained. A method of carrying the antibody by using the quantum dots is adopted, so that a secondary antibody dyeing link in the existing multicolor immunofluorescence technology is omitted, and the efficiency is improved; the quantum dots are used for replacing fluorescent dye, direct marking of tissue slices can be achieved, local positioning of plasma cells and follicular DCs in the thymoma tumor microenvironment is achieved, and both quantity detection and position detection can be achieved.

The invention discloses a chimeric antigen receptor modified cell drug as well as a preparation method and application thereof, and belongs to the technical field of cell drugs. A cell drug is obtained by introducing a chimeric antigen receptor targeting B cells and / or plasma cells into in-vitro or in-vivo immune cells through a gene delivery system, and target spots of the targeted B cells and / or plasma cells comprise CD19, BCMA, CD20, CD22, CD38, CD138, GPRC5D and SLAMF7. The chimeric antigen receptor modified cell drug can realize specific recognition of B cells and / or plasma cells and activate immune cells through a specific single-chain antibody fragment (scFv), and can specifically remove the B cells in vitro and in vivo, thereby preventing the generation of autoimmune antibodies and the formation of immune complexes, achieving the purpose of thoroughly treating diseases, and having good application prospects. The life quality of a patient is improved, the disease is finally cured, and the application potential and the commercial value are huge.

The invention provides genetically engineered fibroblasts, a preparation method thereof, a culture medium for proliferating and / or differentiating B cells and application, and belongs to the technical field of genetic engineering. The genetically engineered fibroblast contains a CD40L gene, an IL-2 gene, an IL-4 gene, an IL-21 gene and a BAFF gene, can express CD40L, IL-2, IL-21, IL-4 and BAFF, can promote B cells to be differentiated into plasma cells, supports proliferation of the B cells, and can prolong the in-vitro survival time of the B cells, so that long-term in-vitro culture and efficient amplification of the low-density B cells are realized. Experimental results show that the genetically engineered fibroblasts constructed by the invention can support in-vitro culture of B cells for more than 16 days, and in-vitro survival of the B cells is effectively maintained. In addition, the cell line can also significantly promote B cells to differentiate into plasma cells and secrete high-level antibodies.

Methods for treating and / or assessing a subject having a symptomatic multiple myeloma or a precursor thereof, where the methods involve characterizing a plasma cell dyscrasia (e.g., monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, multiple myeloma, plasma cell leukemia) in a biological sample from a subject as being high, medium, or low risk by assigning to the plasma cell dyscrasia a multiple myeloma (MM)-like score. The methods may involve sequencing DNA from the biological sample using whole-genome sequencing (WGS).

The invention belongs to the technical field of biological medicines, and discloses a B cell and cartilage cell senescence targeting osteoarthritis treatment medicine. The invention provides an application of an anti-MIF antibody or an antigen binding fragment thereof as a B cell targeting immunomodulator in osteoarthritis treatment drugs, the anti-MIF antibody or the antigen binding fragment thereof regulates and controls an MIF / HMGB1 / MMP13 signal axis through a neutralization effect with MIF, so that the MIF and B cells are significantly co-localized, expression of HMGB1 in the B cells is promoted, and the osteoarthritis treatment effect is improved. The senescence of B cells is reduced and the B cells are promoted to regulate or repair phenotype transformation so as to destroy chronic inflammatory circulation and diffusion of pathogenic plasma cells, and the expression of MMP13 in joint tissues is reduced so as to maintain the steady state of cartilage tissues; the preparation method has an excellent application prospect in preparation of an OA intra-articular injection drug which realizes rapid anti-inflammatory and long-term cartilage protection effects and can realize a lasting curative effect through low-frequency drug delivery.

Disclosed is a method for evaluating the immunostimulatory capacity of a target substance, the method including a contacting step in which a human plasmacytoid dendritic cell line is cultured in the presence of the target substance, wherein the human plasmacytoid dendritic cell line is the CAL-1 cell line (accession number FERM BP-10914), and the CAL-1 cells are in a starvation state during at least part of the contacting step.

To provide an immunostimulating composition.SOLUTION: An immunostimulating composition comprises, as an active ingredient, a bacterium that is phagocytosed by plasmacytoid dendritic cells (pDC) at or above a predetermined level.SELECTED DRAWING: None

The invention discloses a high-precision detection method of abnormal plasma cells, which comprises the following steps: preparing a film, immediately and uniformly mixing the extracted marrow fluid with an anticoagulant, sequentially diluting and centrifuging the marrow, then collecting a leukocyte layer, washing with a fluid medium RPMI 1640 / 5% FBS for at least one time, then counting the cells, adjusting the cell concentration to 1 * 10 < 6 > / ml, adding 100 [mu] l of the cell suspension into a funnel of a cell centrifugal smear device, centrifuging at room temperature for 1000 revolutions, continuing for 5 minutes, and preserving a slide filled with the cell suspension; the preparation of FISH cells comprises the following steps: firstly, preparing and pretreating a 90% formamide / 2 * SSC solution; according to the method, the accuracy and the efficiency of abnormal plasma cell detection are improved by combining an intelligent AI recognition model and a fluorescence in situ hybridization (FISH) technology. The application of the intelligent AI recognition model can reduce personal errors and improve the recognition capability of fluorescence signals, thereby improving the accuracy of detection results.

The present disclosure is concerned with compounds and compositions for use in the prevention and treatment of cancer associated with FBOX21 mediated p85a ubiquitination such as, for example, cancer (e.g., sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, a glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, non-small cell lung carcinoma, renal cancer, lung cancer, colon cancer, cervical cancer, and plasma cell neoplasm (myeloma)). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present disclosure is concerned with compounds and compositions for use in the prevention and treatment of cancer such as, for example, a primary or secondary tumor within a subject's brain, breast, kidney, pancreas, lung, colon, prostate, lymphatic system, liver, ovary, or cervix. Additional examples of cancers for which the disclosed compounds and compositions can be useful include, but are not limited to, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanomas, gliomas, leukemia, lymphoma, chronic myeloproliferative disorders, myelodysplastic syndrome, myeloproliferative neoplasm, non-small cell lung carcinomas, and plasma cell neoplasms (myelomas). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present invention provides a method for culturing immune organoids and its application. The present invention cultures immune organoids by isolating lung-infiltrating lymph nodes and evaluates the level of mucosal immune response produced against influenza virus. By adding components such as BAFF and IL-2 to the cell culture medium and using the air-liquid interface method to three-dimensionally reconstruct immune cells derived from lung-infiltrating lymph nodes, immune organoids with a lymphoid structure are formed. These immune organoids can more realistically reflect the level of local immune response in the lungs and better retain various immune cells. At the same time, T cells are activated, enhancing their helper effect on B cells; the time for B cells to differentiate into plasma cells and mature is greatly shortened, and the efficiency of detecting and evaluating the immunogenicity of viral antigens is improved.

The invention provides a preparation method of a monoclonal antibody of coccidian oocyst protein, and belongs to the technical field of antibodies. The method comprises the following steps: carrying out flow sorting on single antigen-specific B lymphocytes, carrying out stimulated differentiation culture in a specific culture medium by taking EL4B5 as feeder layer cells, cracking obtained plasma cells, carrying out PCR (Polymerase Chain Reaction) amplification to obtain a variable region sequence of a monoclonal antibody, and carrying out recombinant expression to obtain the coccidian oocyst protein monoclonal antibody. The monoclonal antibody of the coccidian oocyst protein provided by the invention comprises at least one of coccidian monoclonal antibodies 6B10, 5C8 and 5D5. According to the present invention, the antigen affinity verification is performed on the monoclonal antibodies obtained through the recombinant expression, and the results show that the three monoclonal antibodies have good antigen affinity and good detection specificity, such that the effective tool is provided for the subsequent diagnosis and detection of the porcine coccidiosis and the porcine coccidiosis infection diseases.