81 results about "Lymphoblastic Leukemia" patented technology

The invention belongs to the technical field of immunoassay and biosensing, and provides a novel construction mode of a heterojunction dual-photoelectrode photoelectric sensing strategy and a preparation method of an in-situ heterojunction MIO photocathode. The invention relates to a preparation method of a heterojunction dual-photoelectrode type photoelectrochemical sensor based on multi-ball cascade DNA reaction amplification. Specifically, the design is composed of an In2O3 / CdS photoanode and an in-situ formed MIL-68 / In2O3 (MIO) photocathode. The heterojunction dual-photoelectrode sensing strategy effectively prolongs an electron-hole transmission path, enhances photo-generated charge separation, and realizes' super-open 'PEC signal output, thereby providing a steady baseline for signal conversion. Meanwhile, a multi-sphere cascade DNA reaction is combined to output a three-dimensional DNA net structure to provide a large number of sites for embedding of a PEC quenching probe doxorubicin-ferrocene carboxylic acid (DOX-FcCOOH), obvious PEC signal quenching is realized by utilizing the efficient competitive electron transfer capability of the three-dimensional DNA net structure, and finally, a signal conversion system with'opening-super opening-closing 'multistage response characteristics is constructed. The detection of the nucleic acid marker Pax-5a gene of the B cell acute lymphatic leukemia is realized by detecting target objects with different concentrations.

This application relates to the technical field of pharmaceutical preparations, and specifically discloses a pharmaceutical composition containing ibrutinib and its preparation method. The composition includes the active ingredient ibrutinib, colloidal silicon dioxide, solubilizers, and other excipients such as excipients; its preparation method is: the active ingredient ibrutinib is preferentially mixed with colloidal silicon dioxide and solubilizers, followed by dry granulation, mixing, and capsule filling. The composition of this application can be used for the treatment of diseases such as mantle cell lymphoma (MCL) / chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma, etc. It can effectively break the insoluble complex salt formed by ibrutinib and solubilizers, and has the advantages of fast dissolution rate and significantly improved bioavailability; in addition, the preparation method of this application has the advantages of good process reproducibility, simple process steps, low production cost, and being suitable for large-scale industrial production.

Provided herein are compositions and methods for treating a relapsed or refractory hematologic cancer in a human patient in need thereof. The methods entail administering to the patient a daily dose of about 10 mg to about 75 mg of cerdulatinib or a pharmaceutically acceptable salt thereof, wherein the patients suffer one or more of a B-cell malignancy, chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) or other transformed FL and / or have relapsed or not responded to a prior chemotherapy.

The present invention relates to a system and a method for measuring and analyzing minimal residual disease (MRD) in pediatric B-cell precursor acute lymphoblastic leukemia (B-ALL) using multiparameter flow cytometry (MPFC). The invention finds application in clinical diagnostics and hematology-oncology for quantifying MRD in B-ALL patients with high sensitivity and specificity, needed for risk stratification, monitoring treatment response, and informing therapeutic decisions. The system comprises interconnected subsystems including an acquisition subsystem with an MPFC instrument, a control and file generation subsystem, and an analytical subsystem. The analytical subsystem incorporates modules for sequential data reduction, automated data cleaning, automated unsupervised data clustering, and interactive cluster analysis. Key advantages include high MRD detection sensitivity (e.g., 10⁻⁵ or 0.001%) and high specificity, without reliance on reference samples or supervised machine learning models, making it applicable in laboratories with different measuring equipment and using different panels of antibodies for identification of leukemic cells.

The present invention provides therapies for the treatment of CCR9 positive cancers, such as T cell acute lymphoblastic leukemia. In particular, the present invention provides a CCR9 targeting moiety. The invention also relates to a CCR9 targeting moiety comprising another targeting moiety, preferably a CD1a targeting moiety, to a dual CAR comprising CCR9 and CD1a targeting moieties, to the use thereof in the treatment of CCR9 and / or CD1a positive cancers, and to the use of a CCR9 targeting moiety and a CD1a targeting moiety alone for such treatments.

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 provides a construction method and a construction system of a chronic lymphocytic leukemia prediction model based on machine learning, electronic equipment and a storage medium, and relates to the field of chronic lymphocytic leukemia prognosis research. The construction method comprises the steps of obtaining original sample data, and performing preliminary screening; performing data cleaning on the screened sample data; determining a prediction factor from the plurality of features of the cleaned sample data; dividing the cleaned sample data corresponding to the prediction factor and the target variable into a training set and a test set; inputting the training set after unbalance processing into a LightGBM model for training to obtain a prediction model; inputting the test set into a prediction model, performing hyper-parameter optimization on the prediction model, and evaluating the performance of the prediction model; calibrating the prediction model to obtain a calibrated prediction model; the method has the beneficial effects that the method can be realized only by depending on conventionally available predictive factors, and the patient screening can be realized before the CLL clinical symptoms appear.

The invention relates to an acute leukemia (ALL) high-throughput flow cytometry kit, and belongs to the field of leukemia detection.16 ALL cell antigens are added on the basis of an original 8-color flow cytometry, 24 antigens in the same cell can be detected at the same time, the detection precision of minimal residual focus (MRD) is greatly improved, and the detection sensitivity is improved. The ALL cells are divided into 12 developmental stages, so that immunological typing during primary diagnosis and immunophenotype variation after bone marrow transplantation and CAR-T cell treatment can be more accurately recognized, and the method has very important guiding significance on evaluation of treatment effects of patients and adjustment of treatment schemes.

The invention discloses a compound for targeted ubiquitination degradation of USP7 protein, and a medicinal composition and application thereof. The structural formula of the E3 ubiquitin ligase complex is as shown in formula I. A is a specific protein ligand in the E3 ubiquitin ligase complex; l is a bivalent linking group between a USP7 protein small molecule ligand and a specific protein ligand in an E3 ubiquitin ligase complex. The protein degradation chimera has the activity of inhibiting USP7 protein and the activity of degrading USP7 protein, and can effectively inhibit malignant proliferation of acute lymphatic leukemia cells, so that the protein degradation chimera can be used for related diseases with abnormal expression of USP7 protein.

The present study of the regulatory T phenotype of Sézary cells led to the discovery of the expression of GARP (LRRC32) by Sézary cells. GARP has also been shown to be overexpressed in samples from patients with acute lymphoblastic leukemia. GARP therefore appears as a diagnostic marker, for monitoring T-cell malignancies, and as a therapeutic target. Accordingly, the present invention relates to methods for the diagnosis and treatment of T-cell malignancies.

Monitoring active disease or progressive disease under therapy in chronic lymphocytic leukemia (CLL) represents a challenge to earlier and better adapt therapeutic strategy, notably in the era of targeted therapies in which minimal residual detection or mutations are sometimes not associated to poor clinical outcome. By following CLL patients before treatment (Binet stages A and B / C) or during targeted therapy, the Inventors developed a new flow cytometric method, based on CD69, CD49d, CD20 and CD279 expression at the surface of CD19+ / CD5+ B leukemic cells. Analyses of these markers alone or in combination show that CD69 / CD49d / CD20 / CD279 co-expression (quadruple population, QP) > 0.5% is the best criterion predicting CLL active disease or progression under therapy. This new flow cytometry immunophenotyping could help clinicians to monitor CLL evolution and quickly adapt their therapeutic strategy. Accordingly, the present invention relates to an ex vivo method for predicting active Chronic Lymphocytic Leukemia (CLL) or progressive CLL under therapy in a subject suffering from CLL, comprising the step of quantifying a population of CD69+ / CD49d+ / CD20+ / CD279+ cells in a sample obtained from the subject.

In one aspect, the disclosure relates to composition and methods for proteolysis-targeting chimeric molecules (PROTACs). In some aspects, the disclosed compounds are useful for modulating LCK tyrosine kinase activity through targeted degradation. In some aspects, the disclosed compounds are orally bioavailable. In further aspects, the present disclosure relates to methods of making the disclosed compounds, pharmaceutical compositions comprising the disclosed compounds, and methods of treating various clinical conditions and disorders using the same, such as T-cell acute lymphoblastic leukemia. 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 disclosure.

The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma, or myelodysplastic syndrome by administration of Compound (I): (I), or a pharmaceutically acceptable salt thereof.

The invention discloses a T cell adapter constructed based on GAS6 as well as a preparation method and application thereof, and relates to the technical field of cellular immunity, and the structure of the T cell adapter comprises an LG1 structural domain of GAS6, a CD3 binding domain, a linker, a marker protein and a fluorescent protein. Through a natural ligand-receptor targeting mechanism, multi-module collaborative design and structural optimization, the problems of high toxicity, single function, complex production process and the like of traditional CAR-T and scFv-BiTE are solved. Experimental data show that the T cell adapter has the advantages of high specificity, controllable immune activation, long-acting stability, easiness in large-scale production and the like, and provides a safer and more efficient immunotherapy strategy for AXL high-expression solid tumors (such as pancreatic cancer, breast cancer, liver cancer, colorectal cancer, lung cancer and the like) and hematoma (acute myelogenous leukemia, chronic lymphocytic leukemia and the like).

Disclosed are novel compounds for use in treating a proliferative disorder such as a cancer. Further disclosed are compositions comprising the novel compounds. Methods of using the disclosed compounds and compositions are further described. The methods include administering one or more of the disclosed compounds for treatment of various proliferative disorders, including an HRAS-driven cancer, a KRAS-driven cancer, a NRAS-driven cancer, Ewing sarcoma, B-cell acute lymphoblastic leukemia, leukemia, lung cancer, non-small cell lung cancer (NSCLC), solid tumor, breast cancer, triple-negative breast cancer (TNBC), hormone-resistant triple negative breast cancer. Further described are combination therapies in which a novel compound is administered in combination with one or more of a MEK inhibitor, a KRAS G12C inhibitor, or a Selective Estrogen Receptor Degrader (SERD) to an individual in need thereof.

The present invention relates to an immune cell co-expressing IL-15 and a chimeric antigen receptor containing an OX40 ligand as an intracellular signal domain, and a composition for preventing or treating cancer comprising the same as an active ingredient. The immune cell shows synergistic tumor cell killing activity through co-expression of the chimeric antigen receptor and IL-15, and the survival rate and the in-vitro proliferation rate of the immune cell are remarkably improved, so that the immune cell can be used as an efficient anti-cancer cell therapy. Particularly, when the chimeric antigen receptor targeting CD5 is expressed, the immune cell can be used as an effective treatment composition for various CD5 positive tumors, including lymphocytic leukemia.

Therapeutic combinations of an AKT inhibitor and a BCL-2 inhibitor; an AKT inhibitor and a glucocorticoid; and an AKT inhibitor, a BCL-2 inhibitor and a glucocorticoid are described. The combinations can be useful in the treatment of acute lymphoblastic leukemia (ALL).

The present invention relates to a novel anti-HLA-DR IgM isotype monoclonal antibody and to the use thereof alone or in addition to anti-CD20 IgG1 or IgM isotype antibodies, in the treatment of B-phenotype lymphoid hemopathies, and in particular of non-Hodgkin lymphoma B, chronic lymphocytic leukemia (CLL) and B-cell malignant lymphoid hemopathies in general.

The present invention provides a culture medium and a culture method for primary human acute lymphoblastic leukemia cells. The acute lymphoblastic leukemia cell culture medium of the present invention comprises a glutamine additive, non-essential amino acids, recombinant human FLT3 ligand, human interleukin-3, human interleukin-7, human interleukin-2, human stem cell factor, and human thrombopoietin. Using the culture medium and culture method of the present invention, acute lymphoblastic leukemia cells can be cultured with higher amplification efficiency and longer in vitro culture time. The present invention also provides methods and applications for using the culture medium to culture primary human acute lymphoblastic leukemia cells in vitro for drug efficacy evaluation and screening.

A novel human T cell acute lymphoblastic leukemia (T-ALL) cell line (ATCC preservation number PTA-125809), referred to as INB16, induces memory-like function thereon when contacted with natural killer cells that have been proved to be capable of identifying and killing cancer cells, including hematological tumor cells and solid tumor cells. Useful applications of the INB16 cell lines include study, administration in vivo, and cancer therapeutic agents comprising non-replication-ability INB16 cells and / or membrane portions thereof for restoring the function of a patient's own NK cells, as well as related methods of treating cancer.

Provided is a pharmaceutical combination comprising an antibody specific for CD19 and a natural killer cell, and a treatment method using the same. Such a pharmaceutical combination is capable of exhibiting synergistic therapeutic effects on a malignant tumor of B-cell origin such as non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and / or acute lymphoblastic leukemia.

Methods and compositions for treating B-cell acute lymphoblastic leukemia (B-ALL) in a pediatric subject are provided. The methods comprise administering to the subject one or more doses of an antibody-drug conjugate, wherein the antibody or antigen-binding fragment thereof specifically binds CD179a.

Provided herein are methods of treating diseases (e.g., proliferative disease (e.g., cancer (e.g., breast cancer, colon cancer, testicular cancer, CNS cancer, stomach cancer, lymphoma (e.g., B-cell lymphoma (e.g., lymphoplasmacytic lymphoma (e.g., IgM secreting lymphoplasmacytic lymphoma (i.e., Waldenstrom's Macroglobulinemia), non-IgM secreting lymphoplasmacytic lymphoma)), diffuse large B-cell lymphoma (e.g., activated B-cell-like (ABC)-DLBCL, germinal center B-cell-like (GBC)-DLBCL), follicular lymphoma, marginal zone B-cell lymphoma, small lymphocytic lymphoma, mantle cell lymphoma), and leukemia (e.g., chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia, myelogenous leukemia (e.g., chronic myelogenous leukemia, acute myelogenous leukemia))))) comprising administering to the subject in need thereof a therapeutically effective amount of Compound (I). Further provided are methods for treating disease resistant to treatment with BTK inhibitors (e.g., ibmtinib). Formula (I)

Disclosed is L-asparagine aminohydrolase and polyethylene glycol conjugate. The polyethylene glycol has a molecular weight less than or equal to about 5000 Da and the protein is an L-asparaginase from Erwinia. The conjugate has a high level of in vitro activity and an unexpected increase in half-life in vivo. Methods of producing the conjugate and methods of using the conjugate in therapy in treatment of cancer, particularly Acute Lymphoblastic Leukemia (ALL). The method is disclosed for use of the conjugate as a second line therapy for patients who have developed hypersensitivity or have had a disease relapse after treatment with other L-asparaginase preparations.

The present invention provides compounds of formula (I) wherein X is selected from the group consisting of ethyl, vinyl, ethynyl and triazinyl; r1 is selected from the group consisting of alkyl, alkoxy, cycloalkyl,-CH2-cycloalkyl,-O-cycloalkyl, halogen, haloalkyl, OH and CN; and R2 is a ring moiety selected from the group consisting of an imidazolyl group, a pyrazolyl group, a 1, 2, 3-triazolyl group, a thiazolyl group, a phenyl group and a pyridyl group, each optionally substituted; the compounds of formula (I) are useful as inhibitors against native BCR-ABL kinase proteins and clinically important BCR-ABL mutations such as T315I, F317L, E255K and Y253F for the treatment of diseases including chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). # imgabs0 #

The invention provides application of chidamide or a derivative thereof in preparation of a medicine for preventing and / or treating acute T lymphocytic leukemia. According to statistics of curative effect data of grouped clinical patients, compared with an existing treatment scheme (the curative effect is 20-30%) for treating acute T-ALL, the pharmaceutical composition provided by the invention has the advantages that the curative effect can be improved to 75%, and remarkable clinical benefits are brought.

Discussed herein are pharmaceutical compositions containing Ibrutinib and processes for preparing them. The compositions may be utilized in the treatment of a variety of conditions including, without limitation, B-cell proliferative disorders such as non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma or burkitt lymphoma), Waldenstrom macroglobulinemia, plasma cell myeloma, chronic lymphocytic leukemia, lymphoma, or leukemia. These compositions are designed for oral ingestion. The compositions are contained within a capsule such as a standard or sprinkle or in a liquid formulation such as a suspension. In one embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. In another embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropylmethylcellulose, citric acid monohydrate, disodium hydrogen phosphate, sucralose, sodium methyl parahydroxybenzoate, sodium ethyl parahydroxybenzoate, concentrated hydrochloric acid, sodium hydroxide, and water.

The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma, or myelodysplastic syndrome by administration of Compound (I): (I), or a pharmaceutically acceptable salt thereof.

Relapsed / refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. CD1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD1a during ontogeny, confining the risk of on-target / off-tumor toxicity. The present invention provides CD1a-targeting moieties comprising a CD1a-which may be placed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLs.