314 results about "Multiple myeloma" patented technology

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.

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 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.

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 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.

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.

The application provides a nanobody targeting human transmembrane activator and calcium modulator and cyclophilin interactor (TACI) and an application thereof, and the antibody is derived from a llama heavy chain antibody variable region. The anti-TACI single-domain antibody NB38 can specifically bind to human TACI with high affinity, can recognize a recombinant TACI protein, can also recognize a TACI with a natural conformation on a cell surface, and can partially block a BAFF / APRIL signal pathway. Based on the nanobody, the application constructs a fusion protein, a chimeric antigen receptor, an effector cell expressing the chimeric antigen receptor, and a double-specific cell linker and other genetically engineered forms. The nanobody can be further extended into a drug coupling form. The product of the application can be used for mediating directional recognition and killing of TACI positive cells, and can be used as a supplement and expansion of BCMA targeted therapy, and provides a new candidate technical scheme for targeted therapy of multiple myeloma and other TACI related diseases.

The invention provides methods of dosing for the treatment of cancers, such as multiple myelomas, with anti-fragment crystallizable receptor-like 5 (FcRH5) / anti-cluster of differentiation 3 (CD3) bispecific antibodies.

The present invention relates to use of a pharmaceutical composition for multiple myeloma containing 5-fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2-yl}pyrimidine-5-yl)oxy]-N,N-di(propan-2-yl)benzamide.

The invention relates to the technical field of biological medicine, and particularly discloses an NSD protein targeted inhibitor and a preparation method thereof.The NSD protein targeted inhibitor is formed by assembling RK-0080552, rosmarinic acid, ferulic acid and TAT cell-penetrating peptide through non-covalent bonds, amino of the RK-0080552, phenolic hydroxyl of the rosmarinic acid and phenolic hydroxyl of the ferulic acid form a hydrogen bond, and the TAT cell-penetrating peptide forms a non-covalent bond. Arginine residues of the TAT cell-penetrating peptide are combined with carboxyl groups of rosmarinic acid and ferulic acid through electrostatic interaction to form a stable three-dimensional supramolecular structure; the preparation method comprises the following steps: respectively dissolving the components, mixing and crystallizing in proportion, washing, homogenizing at high pressure, and freeze-drying to obtain the NSD protein targeted inhibitor. According to the invention, drug activity enhancement and targeted delivery are realized through a supramolecular co-crystal technology, and the drug can be used for treating NSD2 high-expression tumors such as multiple myeloma and acute myelogenous leukemia, and has significant clinical application value.

The present disclosure provides methods of treating multiple myeloma in a subject with a Bcl-2 inhibitor, in particularly 2- ( (1H-pyrrolo [2, 3-b] pyridin-5-yl) oxy) -N- ( (4- ( ( ( (1r, 4r) -4-hydroxy-4-methylcyclohexyl) methyl) amino) -3-nitrophenyl) sulfonyl) -4- (2- ( (S) -2- (2-isopropylphenyl) pyrrolidin-1-yl) -7-azaspiro [3.5] nonan-7-yl) benzamide or a pharmaceutically acceptable salt thereof, or in combination with dexamethasone.

The invention discloses a prediction model system for multiple myeloma venous thromboembolism, and the system comprises a data obtaining module which obtains detection data including baseline data; the data category imbalance processing module is used for performing category imbalance processing according to the baseline data to obtain sample data; the data variable screening processing module is used for carrying out variable screening according to the sample data to obtain characteristic variable data; and the data visualization processing module is used for determining the weight of each variable based on proportional risk regression according to the characteristic variable data, incorporating the weight into a preliminary screening variable, segmenting continuous variables, establishing a point value conversion system, calculating a total score and corresponding to a risk probability, and constructing a data visualization chart. The invention discloses a prediction model system for multiple myeloma venous thromboembolism, a storage medium and a use method, and aims to greatly improve the cross-metal transmission rate of ultrasonic signals and improve the accuracy, stability, convenience and practicability of risk early warning.

The invention belongs to the technical field of biotechnology, and particularly relates to preparation and application of a CAR-NK cell targeting BCMA. According to the invention, an antibody sequence with patent medicine potential is obtained through hybridoma screening, and the sequence has originality. After humanized modification, the antibody still has relatively strong affinity to the antigen. Through CAR-NK preparation, it is found that the cells have a stronger tumor killing effect and have a very good anti-tumor effect in an MM mouse model body. The sequence of the BCMA antibody obtained through screening and the prepared CAR-NK cell targeting the BCMA show a good killing effect in in-vitro cell lines and animal experiments, and have the treatment potential for hematoma such as multiple myeloma.

The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases in a subject, wherein the proliferative diseases include cancer, benign neoplasm, angiogenesis, inflammatory disease, autoinflammatory disease, and autoimmune disease, and the cancer includes leukemia, melanoma, multiple myeloma. Treatment of a subject having a proliferative disease with the compounds or compositions of the present invention can inhibit abnormal activity of cyclin-dependent kinase 7, thus inducing apoptosis and / or inhibiting transcription in the subject.

Provided are: an adeno-associated virus (AAV) vector, the AAV vector comprising a cytokine gene, and the cytokine being selected from any one or two or more of the following: IL3, GM-CSF, IL6, APRIL, and BAFF; an AAV vector combination comprising any two or three or more of said AAV vectors; and a method for constructing an acute myeloid leukemia xenograft non-human animal and a method for constructing a multiple myeloma xenograft non-human animal. In addition, further provided is another adeno-associated virus (AAV) vector, the AAV vector comprising a cytokine gene, and the cytokine being selected from any one or two or more of the following: IL2, IL3, IL6, IL15, THPO, SCF, and GM-CSF; further provided is an AAV vector combination comprising any two or three or more of said AAV vectors; and further provided is the use of the AAV vector and AAV vector combination in the construction of a humanized immune system non-human animal, as well as a method for constructing a humanized immune system non-human animal and a method for promoting the differentiation of human hematopoietic stem cells into CD14+ monocytes and CD66b+ granulocytes.

The present invention provides methods for treating multiple myeloma (e.g., refractory multiple myeloma or recurrent and refractory multiple myeloma) in an individual who has received at least two prior therapies for multiple myeloma. The methods comprise administering to the individual an anti-CD38 antibody, pomalidomide, and dexamethasone. Methods of ameliorating renal damage in an individual having multiple myeloma are also provided.

Provided is a composition which can be a lyophilized preparation solution or a lyophilized powder preparation. The composition comprises a multispecific antibody, a surfactant, a buffer system, and a stabilizer / osmotic pressure regulator. Further provided are a preparation method for the composition and use of the composition, for example, use in treating tumors, especially multiple myeloma.

The invention discloses a risk assessment system for difficulty in cross matching of blood, and relates to the technical field of clinical medical examination and blood transfusion management. The system comprises a data input module, a risk calculation module, a risk layering module and a result output and suggestion module. The data input module obtains key information of a patient, wherein the key information comprises an erythrocyte irregular antibody screening result, multiple myeloma diagnosis, hematology department medical history, age of more than or equal to 60 years, pregnancy-related disease state and blood type identification difficulty; the risk calculation module adopts a preset scoring algorithm to endow each factor with a weight and calculates a total risk score; the risk layering module divides the patients into three levels of low risk, medium risk and high risk; and the result output module provides differentiated clinical management paths corresponding to the risk levels. According to the method, early warning of difficulty in cross matching of blood is achieved through quantitative evaluation, blood transfusion process efficiency can be optimized, clinical risks can be reduced, and the method has good prediction performance (AUC = 0.819) and a high negative prediction value (93.7%).

This invention discloses a class of 2-(2-(quinolin-4-yloxy)ethyl)pyridazine-3(2H)-one compounds, their preparation methods, and applications. The structure of these compounds is shown in general formula (I). This invention also discloses that the above compounds have a significant inhibitory effect on interleukin-1 receptor-associated kinase 1 (IRAK1). These compounds can inhibit the proliferation of various tumor cells, including liver cancer, lung cancer, pancreatic cancer, gastric cancer, kidney cancer, colon cancer, esophageal cancer, glioblastoma, leukemia, multiple myeloma, and other solid tumors and hematological malignancies. This invention provides a new option for tumor treatment.

The invention discloses a series of colchicine deuterated derivatives for resisting multiple myeloma, which can effectively inhibit proliferation of multiple myeloma cells by improving the metabolic effect of colchicine in the multiple myeloma cells and overcome the defect of large toxic and side effects of metabolism of original drugs. According to the series of colchicine deuterated derivatives capable of resisting multiple myeloma, colchicine is used as a raw material, two reactions of demethylation and deuterated methyl are sequentially performed to obtain a target compound, the reaction steps are few, the reaction conditions are mild, the operability is high, and the efficiency is high.

Provided herein are methods and uses of combination therapies involving a GPRC5D-targeted cell therapy comprising a chimeric antigen receptor (CAR) containing an extracellular antigen binding domain that binds to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and a combination agent, e.g., a bispecific antibody, for treating a subject having a cancer, such as multiple myeloma, as well as related methods, uses, and articles of manufacture.