449 results about "Multiple myeloma" patented technology

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 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.

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

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.

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 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.

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.

The present disclosure provides methods of treating multiple myeloma in a patient in need thereof comprising administering a gamma secretase and a B-cell maturation antigen (BCMA)-directed therapy to the patient.

The disclosure concerns a method of treating cancer, especially, such as multiple myeloma, involving the combination of an anti-BCMA (B cell maturation antigen) antibody, Belantamab mafodotin -GSK2857916- and a gamma-secretase inhibitor, e.g., nirogacestat -PF03084014-. The disclosure also relates to dosages, duration of treatment and time lapses between administration of the anti-BCMA antibody and the gamma-secretase inhibitor.

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 relates to the technical field of nano antibodies, in particular to an anti-FcRH5 nano antibody and application thereof. The invention provides an anti-FcRH5 nano antibody with high affinity and specificity, and the anti-FcRH5 nano antibody is based on a single-domain heavy chain variable region structure from camelidae and has the advantages of small molecular weight, high stability, strong tissue penetrability, easiness in engineering modification and the like. The nano antibody specifically recognizes and is combined with a high-expression and stable-expression target spot on the surface of a multiple myeloma cell through a complementary determining region of the nano antibody. The nano antibody disclosed by the invention can be used as a core recognition element for constructing various treatment or diagnosis tools such as chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates or immunodetection probes and the like. According to the technical scheme, the technical problem that an anti-FcRH5 antibody with high quality and definite functionality is lacked in the prior art can be solved. The nano antibody provided by the invention has remarkable clinical transformation and industrialization advantages, and promotes multiple myeloma treatment to multi-target collaborative iteration.

The invention discloses a therapeutic target CD40 related to multiple myeloma bone diseases and application of a monoclonal antibody of the therapeutic target CD40. On one hand, it is found that formation and osteogenic differentiation of primary cilia of BMSCs can be effectively recovered by adding a CD40 neutralizing antibody into an MM-BMSCs co-culture system; on the other hand, the CD40 neutralizing antibody is found to reduce bone destruction and tumor load in a Vk * MYC myeloma mouse model. CD40 is expected to become a potential target spot for treating multiple myeloma bone diseases and has a very wide application prospect in the field of medical research.

Described herein are methods of treating malignancies such as tumors or cancers by orally administering lyophilized compositions comprising arsenic to a subject in need thereof. Malignancies include various hematological malignancies, such as acute myeloid leukemia (AML) including acute promyelocytic leukemia (APL), myelodysplastic syndrome (MDS), multiple myeloma (MM) and lymphomas, and solid tumors including glioblastoma multiforme and breast cancer. Also described herein are oral pharmaceutical formulations comprising lyophilized compositions comprising arsenic and methods for lyophilizing arsenic trioxide, preparing the oral formulation comprising lyophilized compositions comprising arsenic, and treating a subject with malignancies using the oral formulation.

The invention relates to application of SMARCC1 in preparation of a medicine for treating carfilzomib-resistant multiple myeloma, and belongs to the technical field of biological medicine. According to the invention, direct association between SMARCC1 and the drug resistance of multiple myeloma to carfilzomib is determined for the first time, and the sensitivity of drug-resistant cells to carfilzomib can be significantly enhanced by down-regulating the expression of the gene. Specifically, through systematic analysis on clinical data, SMARCC1 is found to be remarkably and highly expressed in relapse / refractory MM patients and is closely related to poor survival. The SMARCC1 knock-down obviously inhibits the multiplication capacity of multiple myeloma drug-resistant cells, so that the SMARCC1 not only promotes the multiplication capacity of the drug-resistant cells, but also is closely related to the drug resistance of the multiple myeloma cells to carfilzomib, which prompts that the SMARCC1 can be used as a potential therapeutic target and is used for reversing the carfilzomib drug resistance of multiple myeloma.

The invention discloses a 2-amino-4-(5-cyano-1-isopropyl-1H-indole-3-yl) pyrimidine compound and application thereof, the compound has the following structural general formula: in the formula, substituent R is substituted phenyl, the number of substituent groups on the benzene ring of the substituted phenyl is 1-2, and the substituent groups on the benzene ring of the substituted phenyl are 1-2. Substituent groups are respectively and independently selected from nitro, cyano, halogen, carbamoyl, furyl or pyridyl. The 2-amino-4-(5-cyano-1-isopropyl-1H-indole-3-yl) pyrimidine compound designed and synthesized by the invention is a novel efficient NF-kappa B induced kinase (NIK) inhibitor, and is suitable for drug development taking NF-kappa B induced kinase (NIK) as a target spot, and the obtained drug can be used for treating malignant tumors such as leukemia, multiple myeloma and the like.

Cell surface polypeptides SEMA-4A and FCRL3 have been identified as being associated with multiple myeloma. Accordingly, these peptides represent targets for immuno-based therapeutic strategies for treating multiple myeloma. Antibodies that specifically binds to one of these polypeptides can be used to treat multiple myeloma. Accordingly, new compositions and methods utilizing novel antibodies that target SEMA-4A and FCRL3 are described.

Embodiments described herein relate to methods of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, and pomalidomide, to the subject to treat the multiple myeloma.

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and / or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

The application discloses a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative and a synthesis method and application thereof, and relates to a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative which is a compound with the following general formula (I): wherein R1 is selected from,,,,,,,,, and R2 is selected from,,, and. The compound can significantly inhibit the proliferation of leukemia, multiple myeloma, lymphoma, breast cancer, liver cancer and the like at a low dose (nanomole), can effectively degrade IKZF1, IKZF3, BRD4, GSPT1 and CK1 alpha, and has the prospect of being developed into an anti-tumor drug. The application solves the problem that the existing malignant hematological disease treatment drugs have a high safety risk.

The invention provides a 1-methyl-6-oxyindole-2-formamide derivative as well as a preparation method and application thereof, and belongs to the field of drug synthesis, the structural formula of the 1-methyl-6-oxyindole-2-formamide derivative is shown as a general formula I: # imgabs0, R1 is selected from # imgabs1, # imgabs2, # imgabs3, G = C or N, R2 is selected from a group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 8, 9, 10, 12, 13, 14, 16, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17 W = C or N. The 1-methyl-6-oxoindole-2-formamide mother nucleus group with biological activity contained in the compound is further chemically modified to generate a plurality of compounds with higher biological activity, so that the wide application of the compounds in biological medicines and the development prospect of pharmaceutical preparations are expanded. The compound can significantly inhibit proliferation of breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma and other cells at a low dosage (nanomole), and can effectively inhibit STAT3 protein phosphorylation, which shows that the compound has a prospect of being developed into antitumor drugs.

Provided herein are methods of treating cancer in a subject in need thereof by administering an anti-BCMA CAR-T cell and a GPRC5D×CD3 bispecific antibody. In some embodiments, the subject has relapsed and / or refractory multiple myeloma. In some embodiments, the subject has received at least one prior line of therapy. In some embodiments, the subject has newly diagnosed multiple myeloma and is transplant ineligible.

Anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and chimeric antigen receptors (CARs) are provided herein. Also provided are polynucleotides encoded the anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and CARs. The anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and CARs are useful for the prevention and / or treatment of cancer, such as multiple myeloma. Also provided is a combination therapy including administration of the anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and CARs with an IL-16 or an IL-15 agonist.