547 results about "Multiple myeloma" patented technology

Provided are an anti-BCMA single-domain antibody, and a preparation method therefor and the use thereof. Specifically, provided is a single-domain antibody having an amino acid sequence of SEQ ID No. 1. The single-domain antibody has high affinity, can thoroughly specifically target BCMA-positive cells, and can be applied to the detection of BCMA expression in bone marrow cells of MM patients. The single-domain antibody can be prepared into a specific antibody drug clinically used for preventing and treating BCMA-target-related diseases (such as multiple myeloma, B-cell acute lymphoblastic leukemia, non-Hodgkin's lymphoma and Hodgkin's lymphoma); or a BCMA protein detection kit, etc. The single-domain antibody has a stable structure, a small molecular size, is easily recombinantly expressed and has a low production cost, can be used alone or as a drug delivery system to carry relevant drugs, and has very wide prospects and important significance in fields such as drug application and clinical diagnosis.

The invention provides the GPRC5D single domain and the humanized antibody thereof, the GPRC5D single domain and the humanized antibody thereof have relatively strong binding activity and reaction specificity, also have good species cross reactivity, are of great significance in research and development in different species models, and are beneficial to acceleration of a transformation process from a laboratory to clinic. The antibody sequence provided by the invention can be used for constructing CAR-T, and can be used for treating multiple myeloma.

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

The invention relates to the technical field of clinical medicine, in particular to a prognosis risk assessment model of multiple myeloma as well as a construction method and application of the prognosis risk assessment model. Compared with the prior art, the prognosis risk assessment model for multiple myeloma provided by the invention has the advantages of wider coverage, higher prediction accuracy and higher layering ability. The sample data of the model is from a large queue of newly-diagnosed multiple myeloma patients of multiple medical centers in China, so that compared with other similar international models, the model is more in line with clinical, biological and prognosis characteristics of Chinese people, and has greater advantages in Chinese people.

The invention discloses a multiple myeloma bone marrow image recognition system based on computer vision, relates to the technical field of cell recognition, solves the problem that traditional manual microscopic examination is large in limitation, and accurately recognizes burr change segments by conducting angle analysis on the edge contour of a feature area, so that the accuracy of recognition is improved. According to the comprehensive proportion of the burr change section on the overall edge contour, reliably judging whether the to-be-detected cell is a tumor cell or not, and calibrating and displaying the tumor cell in a gray image; according to the mode, the obvious difference of the tumor cells and normal cells in cell nucleus morphology is effectively utilized, rapid and accurate identification of the tumor cells is achieved, a visual and clear result is provided for clinical diagnosis, doctors are assisted to accurately judge multiple myeloma in time, the diagnosis efficiency and the treatment effect are improved, mean value processing and radial ratio analysis are conducted on contour area gray values, and the diagnosis accuracy is improved. The contour region associated with the cell nucleus can be accurately locked from the to-be-detected cell and is calibrated as the feature region, and a key cell nucleus feature basis is provided for tumor cell recognition.

A drug combination of purinostat mesylate and an analog thereof for preventing and treating multiple myeloma, and the use thereof. Specifically, provided is a three-drug or four-drug combination of purinostat mesylate and an analog thereof, dexamethasone and other drug, which drug combination has significantly enhanced synergistic anti-tumor activity in vitro and in vivo, synergistically inhibits the expression of the key survival protein in multiple myeloma, is superior to existing clinical combination regimens, and has no significant toxic side effects. In addition, the drug combination significantly down-regulates the expression of CDK6, and overcomes the drug resistance to an immunomodulator. In particular, the three-drug combination of puisostat mesylate, a glucocorticoid and an immunomodulator has an excellent prevention and treatment effect on multiple myeloma, especially relapsed / refractory multiple myeloma.

An antibody capable of binding to LILRB4 and a bispecific antibody capable of binding to LILRB4 and CD3 are provided. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. Also provided are methods of treating solid tumors, multiple myeloma or leukemia, such as acute myelogenous leukemia (AML), using the anti-LILRB4xCD3 double antibodies of the present invention.

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a cyclophosphamide ternary nano-micelle and a preparation method thereof.The cyclophosphamide ternary nano-micelle prepared through the method can be used for treating malignant lymphoma, multiple myeloma, leukemia, breast cancer, ovarian cancer, cervical cancer, prostatic cancer, colon cancer, bronchial cancer, lung cancer and the like. Reasonable preparation steps and a preparation formula are adopted, the use of an organic reagent is reduced, the irritation of cyclophosphamide is reduced and the stability of the micelle is improved by adjusting a freeze-drying technology, and the cyclophosphamide micelle adopts amphiphilic macromolecules as a carrier material, so that the drug loading capacity and the stability of the micelle are obviously improved, and the bioavailability of the micelle is improved. The ternary nano-micelle system has the advantages that the solubility of cyclophosphamide is improved, the in-vivo bioavailability is increased, the preparation method is simple, the micelle performance is stable, and large-scale industrial production is facilitated.

The invention discloses an intelligent auxiliary decision-making method and system for multi-modal data fusion of multiple myeloma, and relates to the technical field of medical information, and the method comprises the steps: obtaining multi-source clinical data and authoritative literature of a patient, and building a literature database after preprocessing; configuring an interface to automatically capture new literatures, and generating a dynamic knowledge base in combination with semantic conflict detection, knowledge extraction and expert auditing; according to the knowledge base, fusing the multi-modal clinical data by adopting federal learning to generate a fusion feature matrix; constructing a causal relationship network, combining matrix prediction and generating a causal evidence network, and grading the causal relationship; and associating the knowledge base with the evidence network, generating an interpretable report containing a prediction result and the like, and realizing full-process traceability. Through three designs such as automatic knowledge acquisition and updating, the static lag problem of the knowledge base is broken through, and the medical frontier is synchronized; a causal reasoning system is constructed, defects of a traditional model are overcome, transparent reasoning is achieved, and the credibility of doctors is improved.

Embodiments of the present invention relate to methods of treating multiple myeloma in a subject in need thereof comprising administering to the subject a BCMAxCD3 bispecific antibody on a bi-weekly dosing schedule.

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 invention discloses a multiple myeloma patient nursing management system and method, and relates to the technical field of medical nursing, and the method comprises the steps: obtaining the medical data of a multiple myeloma patient through a data fusion platform, and integrating the medical data through a multi-source heterogeneous data set; making a medical plan for the multiple myeloma patient based on the preprocessing result of the medical data; and performing intervention suggestion on the medical plan according to the medical treatment decision model to complete nursing management of the multiple myeloma patient. According to the method, efficient integration and high-quality processing of medical data are achieved, abnormal data can be recognized and repaired in time, the accuracy and safety of a medical plan are ensured, and the nursing quality and the treatment effect of multiple myeloma patients are remarkably improved in combination with intervention suggestions of a medical treatment decision model.

The invention discloses a method for researching the influence of triptolide on the proliferation of multiple myeloma cells by regulating miR-381 / HMGB1 (High Mobility Group Box 1), and relates to the technical field of biology. Research results of the research method show that miR-381 methylation silencing in RPMI8226 cells is an important reason for promoting cell proliferation, TPL inhibits proliferation of the RPMI8226 cells by reversing a miR-381 methylation modification state, inducing and restoring expression and regulating HMGB1 genes in a targeted manner, and the research lays a theoretical basis for exploring an anti-MM action mechanism of TPL.

The invention discloses a chimeric antigen receptor simultaneously targeting GPRC5D and CS1 and application thereof, and relates to the technical field of biological medicines. Spatial epitopes of a GPRC5D antigen and a CS1 antigen are taken as target spots, an scfv region of a GPRC5D antibody and an scfv region of a CS1 antibody are connected in series through Linker, and an optimal structure VH1-VL1-VH2-VL2 is obtained through screening, VH1 and VL1 are anti-GPRC5D scfv, and VH2 and VL2 are anti-CS1scfv. The chimeric antigen receptor constructed by connecting the optimal structure VH1-VL1-VH2-VL2 with a transmembrane region of CD8, a CD137 intracellular signal region and a CD3zeta intracellular signal region in series is used for treating the multiple myeloma, so that the problems of low remission rate and high relapse rate of a CAR-T cell therapy in treatment of the multiple myeloma are solved, and the chimeric antigen receptor is still effective for the multiple myeloma with BCMA negative or low BCMA antigen expression and can be used for treating the multiple myeloma. And a new strategy is provided for clinical treatment of multiple myeloma patients with negative BCMA expression or recurrence after BCMA CAR-T treatment.

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

The present application relates to a multispecific binding molecule that targets BCMA, GPRC5D, and T cell receptors. Specifically, the invention discloses a BCMA-GPRC5D-CD3 multispecific antibody which can activate T cells while being combined with a tumor surface antigen, thereby promoting the specific killing of the T cells on tumor cells, especially BCMA or GPRC5D positive multiple myeloma. The invention also provides a preparation method and application of the multispecific binding molecule.

The present disclosure relates to multifunctional binding proteins comprising a first and a second antigen binding domains (ABDs) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human BCMA and the second ABD binds specifically to human NKp46 and wherein all or part of the immunoglobulin Fc region or variant thereof bind to a human Fc-γ receptor.The disclosure also relates to methods for making said binding proteins, compositions thereof, and their uses, including the treatment or prevention of proliferative disorders, including multiple myeloma (MM).

The invention discloses a nano antibody targeting GPRC5D as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The nano antibody is generated by mixed immunization of a GPRC5D polypeptide antigen with a sequence shown as SEQ ID NO: 1 and a GPRC5D protein antigen with a sequence shown as SEQ ID NO: 2. The preparation method comprises the following steps: mixing the GPRC5D polypeptide antigen and the GPRC5D protein antigen to immunize alpaca, sampling blood, constructing an antibody library, screening a phage display antibody library, expressing protein, and selecting the nano antibody with the highest affinity. The invention further provides a radionuclide labeled molecular probe, the nano antibody is small in molecular weight and can recognize a large number of epitopes, and the molecular probe prepared from the nano antibody can obtain high-quality images, is used for preparing products for developing multiple myeloma or detecting GPRC5D expression level and has wide application prospects.

Provided is a circular RNA encoding CARs and the use thereof to create immune cells that target specific diseases, e. g., lymphoma, multiple myeloma and leukemia and auntoimmune diseases, such as systemic lupus erythematousus, lupus nephritis and myasthenia gravis.

A fully human antibody targeting GPRC5D and a chimeric antigen receptor (CAR) comprising the fully human antibody. A host cell expressing the CAR, such as a CAR-T cell. A use of the fully human antibody, the CAR, and the CAR-T cell in treatment of tumors (such as multiple myeloma).

The invention relates to a multiple myeloma model with extramedullary lesion as well as a construction method and application thereof. The multiple myeloma model is obtained by injecting bone marrow mononuclear cells (BMMC) of a multiple myeloma patient into an hIL-6NSG mouse. The invention provides a new model of multiple myeloma with extramedullary lesion, which not only is beneficial to research on gene pathway and mechanism of the multiple myeloma, but also lays a foundation for research on tumor recurrence, preclinical drug screening, effect evaluation and the like, and has great significance in promoting disease healing.

The invention provides a single-domain antibody capable of specifically recognizing GPRC5D, which has relatively strong binding activity and reaction specificity, also has good species cross reactivity, is of great significance to research and development in different species models, and is beneficial to acceleration of a transformation process from a laboratory to clinic. The antibody sequences A12 and C07 provided by the invention can be used for constructing chimeric antigen receptor T cells, and the chimeric antigen receptor T cells can be used for treating multiple myeloma.

The invention provides improved anti-BCMA CAR T cell compositions for adoptive T cell therapy for relapsed / refractory multiple myeloma.

The present disclosure relates to multifunctional binding proteins comprising a first and a second antigen binding domains (ABDs) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human BCMA and the second ABD binds specifically to human NKp46 and wherein all or part of the immunoglobulin Fc region or variant thereof bind to a human Fc-γ receptor.The disclosure also relates to methods for making said binding proteins, compositions thereof, and their uses, including the treatment or prevention of proliferative disorders, including multiple myeloma (MM).

Provided herein are biomarkers and combinations of biomarkers for use in manufacturing panels for determining whether a patient is at risk for multiple myeloma precursor disease progression. Also provided herein are methods of treatment for subjects identified as being at risk for multiple myeloma precursor disease progression.

Provided are a chimeric antigen receptor, and a GPRC5D antibody-containing chimeric antigen receptor and a use thereof. The chimeric antigen receptor comprises: an extracellular domain, wherein the extracellular domain is capable of binding to a tumor antigen; a transmembrane domain, wherein the transmembrane domain is connected to the extracellular domain, and the transmembrane domain is derived from an I-type transmembrane protein or an artificially synthesized transmembrane protein having a hydrophobic helix; and an intracellular domain, wherein the intracellular domain is connected to the transmembrane domain, and the tumor antigen is a tumor-specific antigen or a tumor-associated antigen. The amino acid sequence of the transmembrane domain is optimized, thereby providing a GPRC5D antibody-containing chimeric antigen receptor and engineered immune cells; and the engineered immune cells obtained on the basis of the GPRC5D antibody have specific killing performance on multiple myeloma.

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.

Compositions and methods are provided to treat and prevent cancers, such as myelomas, and include adoptive cell therapies in combination with an IL-15 superagonist and one or more chemotherapeutic agents.

Provided herein are methods of treating a subject who has multiple myeloma and has received one to three prior treatment(s). Infusions of chimeric antigen receptor (CAR)-T cells comprising a CAR capable of specifically binding to an epitope of BCMA are administered to the subject.