374 results about "CD38" patented technology

The present invention relates to methods of treatment of light chain amyloidosis and other CD38-positive hematological malignancies with anti-CD38 antibodies.

The present invention relates to methods of immunomodulation and treating patients having solid tumors with antibodies that specifically bind CD38.

Provided herein are common light chain bispecific antibodies that bind CD38 and CD19. The common light chain bispecific antibodies comprise an anti-CD38 heavy chain variable region and anti CD19 heavy chain variable region that each have a negatively-charged amino acid at a terminal heavy chain variable region position. The common light chain bispecific antibodies comprise further comprise an anti-CD38 heavy chain constant region and anti-CD19 heavy chain constant region that each lack a C-terminal lysine residue. Further provided are nucleic acids encoding such common light chain bispecific antibodies and host cells comprising the nucleic acids. Also provided are methods of making such common light chain bispecific antibodies.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

This disclosure provides an antibody or antigen-binding fragment or derivative thereof that specifically binds to CD38. Also provided are polynucleotides encoding the antibody or antigen-binding fragment or derivative thereof and vectors and host cell comprising said poly nucleotides. This disclosure further provides methods for producing and / or using an antibody or antigen-binding fragment or derivative thereof that specifically binds to CD38.

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.

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.

The invention discloses a method for constructing a differential diagnosis model for lupus nephritis and membranous nephropathy, and belongs to the technical field of intelligent medical treatment. The modeling method comprises the following steps: S1, respectively collecting flow cytometry detection data of lupus nephritis patients and healthy control personnel; s2, performing data cleaning and conversion on the flow cytometry detection data, and converting non-numerical features into digits; carrying out implication on the missing value by adopting a k nearest neighbor algorithm from an implication packet; s3, random sampling is carried out on the cleaned and converted data set, and samples are divided into a training set and a verification set according to the proportion of 7: 3; s4, dividing a training subset and a test set from the training set, and iteratively selecting the types of cells incorporated into the constructed model as pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T, and CD38 + PD-1 + CD8T by adopting an RFE method, wherein the types of the cells incorporated into the constructed model are pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T and CD38 + PD-1 + CD8T; and S5, performing a classification task by adopting TabPFNClassifier, performing training from features selected from the training data set, then evaluating the performance of the model, performing model training by utilizing detection data, and performing evaluation to construct a lupus nephritis prediction model with high accuracy.

The invention discloses a computer device and a computer readable storage medium for evaluating the immune reconstitution state of an HIV infected person after ART. Belongs to the field of computer information. The technical problem to be solved by the invention is how to evaluate the immune reconstruction state of an HIV infected person after ART. The invention provides a computer program stored in a memory in a computer device. The computer program comprises the following steps: S1, receiving sample data, namely the proportion of the number of cells expressing PD-1 in CD8 + T cells of peripheral blood mononuclear cells of an HIV infected subject after ART and the proportion of the number of cells expressing at least one of the following five factors: CD38, HLA-DR, CD57, PERFORIN and CD107A; s2, obtaining a predicted value Y from the sample data through a model formula, and outputting an immune reconstruction condition according to the predicted value Y and a pre-judgment condition; the method can accurately and efficiently determine whether the immune reconstruction state of the HIV infected person subjected to antiviral treatment is good or not.

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.

The present invention relates to treatment of IgE-mediated disease with antibodies that specifically bind CD38.

The invention discloses an antibody combination and a system for detecting leukemia stem cells. The antibody combination comprises a CD7 antibody, a CD371 antibody, a CD34 antibody, a CD45RA antibody, a CD123 antibody, a CD133 antibody, a CD38 antibody, a CD45 antibody, a CD90 antibody, a CD33 antibody and a CD19 antibody. The antibody combination provided by the invention can accurately identify target cells and distinguish normal HSCs and pluripotent progenitor cells in a CD34 + CD38-cell population, and the specific antibody has abnormal expression or expression intensity change, so that leukemia stem cells can be rapidly, simply and conveniently detected with high accuracy, high sensitivity and high specificity, the sensitivity of MRD evaluation is favorably improved, and the kit has a good application prospect. Therefore, signs of disease recurrence can be found earlier, more information about disease prognosis can be provided, and doctors and patients can be helped to better understand disease prognosis and possible results.

The present invention provides an antibody composition for detecting multiple myeloma based on full-spectrum flow cytometry and its application, belonging to the technical field of multiple myeloma detection. The antibody composition includes CD3 antibody, CD20 antibody, HLA-DR antibody, CD8 antibody, CD11b antibody, CD10 antibody, CD71 antibody, CD28 antibody, CD14 antibody, CD13 antibody, Igκ antibody, CD15 antibody, Igλ antibody, CD117 antibody, CD56 antibody, CD45 antibody, CD19 antibody, CD34 antibody, CD138 antibody, CD4 antibody, CD38 antibody, CD22 antibody and CD27 antibody. The kit containing the antibody composition can be applied to a full-spectrum flow cytometer to accurately perform preliminary screening on patients with multiple myeloma.

The present invention relates to novel trispecific heterodimeric immunoglobulins. More specifically, the present invention relates to trispecific heterodimeric immunoglobulins that target a human CD3 antigen, a human BCMA, and a human CD38 antigen. The invention also relates to such novel trispecific heterodimeric immunoglobulins for use in the treatment of proliferative diseases and in particular cancers such as hematological cancers. The present invention relates to novel trispecific antibodies for the treatment of multiple myeloma.

The embodiment of the invention relates to the technical field of drug detection, in particular to an anti-CD38 antibody drug receptor occupation detection method and system, a peripheral blood sample is used for preparing a single-cell suspension, the single-cell suspension is divided into a TEST tube and an FMO tube, a cell surface antibody and an RO detection antibody are added into the TEST tube, only the cell surface antibody is added into the FMO tube, and only the RO detection antibody is added into the FMO tube. The TEST tube and the FMO tube are subjected to sample detection analysis, so that the average fluorescence intensity of RO detection antibodies of the TEST tube and the FMO tube is obtained. And performing RO detection analysis by adopting a dissociation method, taking the tubes which are not combined with the medicine as a total receptor group, taking the tubes which are combined with the medicine as a dissociation receptor group, and calculating an RO detection result according to the average fluorescence intensity of the TEST tube and the FMO tube.

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.

The present invention relates to treatment of IgE-mediated disease with antibodies that specifically bind CD38.

The invention provides an anti-CD38 nano antibody as well as a preparation method and application thereof. Specifically, the invention provides an anti-CD38 nano antibody, an anti-CD38 antibody, a corresponding humanized antibody, a chimeric antigen receptor, a fusion protein, a recombinant protein, polynucleotide, an expression vector, a host cell and the like, as well as a preparation method and application of the anti-CD38 nano antibody and the anti-CD38 antibody. The anti-CD38 nano antibody provided by the invention can reach a protein concealment epitope which cannot be approached by a conventional antibody, can reach higher affinity compared with the prior art, is superior to a positive control Darumumab, and has higher patent medicine value and potential.

The present disclosure provides methods for treating multiple myeloma comprising administering an anti-CD38 antibody and an Interleukin-2 analog to an individual in need thereof and optionally administering Natural Killer (NK) cells having expression of CD38 reduced or knocked-out.

The present invention relates to compositions comprising NAD and, in some preferred embodiments, further comprising a CD38 inhibitor, an antioxidant, an endogenous cellular health molecule and / or a sirtuin activator as adjuncts. The present invention also relates to pharmaceutical compositions, dosage forms and methods for NAD delivery and supplementation.

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 belongs to the technical field of antibody preparation, and particularly relates to an anti-CD38 nano antibody as well as a preparation method and application thereof. The method comprises the following steps: constructing and expressing CD38 antibody protein, immunizing alpaca, obtaining immune alpaca PBMC (peripheral blood mononuclear cells), extracting RNA (ribonucleic acid) of the cells, carrying out reverse transcription to obtain cDNA (complementary deoxyribonucleic acid), carrying out PCR (polymerase chain reaction) to obtain antibody gene segments, constructing the antibody gene segments on a phage expression vector to construct a CD38 immune antibody library, carrying out two rounds of panning, carrying out Clone ELISA (enzyme-linked immuno sorbent assay) detection on clones to obtain an antibody combined with the CD38 protein, carrying out sequencing analysis, and selecting a unique sequence. High-throughput expression is carried out through a mammalian cell high-throughput expression system, antibody protein is obtained, FACS detection is carried out through a CD38 high-expression cell line, and finally the antibody combined with CD38 is obtained. The method is simple and rapid to operate, a mammalian cell expression system induces efficient expression of the antibody, processing modification can be performed after translation, and the activity of the antibody is closer to that of a natural antibody.

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38′ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and / or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

The invention discloses a lupus nephritis marker and application thereof, and belongs to the technical field of biomarkers. The marker for the lupus nephritis, disclosed by the invention, comprises one or more of CD8, CD38 and PD-1. By detecting specific cell surface markers in patient blood, early diagnosis of LN is assisted in a minimally invasive mode, and based on deep comparative analysis of LN patients and healthy people, the specificity and sensitivity of the biomarkers in LN diagnosis are ensured through screening of the biomarkers. In the aspect of differential diagnosis, a clinician is assisted to distinguish LN from other types of kidney diseases, such as membranous nephropathy (MN) and anti-neutrophil cytoplasm antibody related vasculitis (AAV), by analyzing specific biomarker modes of different nephropathy. The dependence on kidney puncture is reduced, related potential risks and inconvenience are avoided, and meanwhile more accurate and timely diagnosis is provided for an SLE patient.

The present invention provides a cytotoxic immunocompetent cell that is derived from a pluripotent stem cell and that expresses a chimeric antigen receptor comprising an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signaling domain. The extracellular antigen-binding domain recognizes CD38 as an antigen. The present invention also provides a pharmaceutical composition or the like comprising the cytotoxic immunocompetent cell derived from a pluripotent stem cell.

Genetically engineered cells (e.g., HSPCs or T cells) having one or more genetically edited cell surface protein genes, such as hematopoietic stem cells, and therapeutic uses thereof, alone or in combination with immunotherapy targeting the cell surface proteins.

Provided is a bispecific chimeric antigen receptor targeting CD38 and CLL1. The chimeric antigen receptor at least comprises, from the N-terminus to the C-terminus: i) an antigen-binding domain that specifically recognizes CLL1 and CD38; ii) a transmembrane domain; iii) at least one co-stimulatory domain; and iv) a signaling domain. A dual-targeting CAR-T cell prepared by using the chimeric antigen receptor described above shows highly specific in-vitro cytotoxicity against CLL1-positive and / or CD38-positive target cells.