33 results about "Lymphoblastic Leukemia" patented technology

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 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 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.

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.

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.

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).

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)

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 present disclosure relates to anti-SAA antibodies or fragments thereof, such as antibodies against human SAA1 or fragments thereof, that may be used in various therapeutic, prophylactic and diagnostic methods. The present antibodies or fragments thereof may be used to treat hematologic disorders such as acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome.

The present disclosure provides methods for treating Philadelphia chromosome positive (Ph +) leukemia, such as CML (chronic myeloid leukemia, chronic myeloid leukemia, chronic myeloid SOS-1 inhibitors (such as bicyclic or macrocyclic compounds) of Ph + ALL (acute lymphoblastic leukemia), Ph + AML (acute lymphoblastic lymphoma), alone or in combination with TKI (such as dasatinib or imatinib) against BCR-ABL tyrosine kinases are disclosed.

The present application relates to a kind of acute leukemia (ALL) high flux flow detection kit, belong to leukemia detection field, the present application is based on the original 8 color flow to increase 16 kinds of ALL cell antigen, can realize the simultaneous detection of 24 kinds of antigens in the same cell, not only greatly improve the detection precision of micro residual lesion (MRD), and by being divided into 12 development stages to ALL cell, can more accurately identify immunotyping when first diagnosis, and immunophenotypic aberration after bone marrow transplantation and after CAR-T cell therapy, this has very important guiding significance to the evaluation of patient treatment effect and the adjustment of treatment scheme.

The present invention relates to a reagent panels for the measurement of minimal residual disease (MRD) associated with pediatric B-cell precursor acute lymphoblastic leukemia (B- ALL) by multiparametric flow cytometry. The reagent panel of the invention comprises a combination of antibodies directed against markers, wherein the combination of antibodies comprises i) antibodies targeting markers CD45, CD20, CD34, CD38, CD10, CD58, CD66c, CD73, CD81, CD123, CD304, CD44, CD86, CD99 and CD371, and ii) antibodies targeting markers CD19 and / or CD22, wherein the antibodies are conjugated with fluorochromes. The invention further relates to the use of said panels for detecting MRD associated with B-ALL and / or for identifying a subject at risk of developing B-ALL relapse. The invention also relates to methods of detecting MRD associated with B-ALL. Key advantages of the invention include achieving high MRD detection sensitivity (e.g., 10⁻⁵ or 0.001%) and high specificity.

Provided herein are, inter alia, novel antibodies that bind to fms-like tyrosine kinase 3 (FLT3) thereby effectively targeting cells expressing FLT3. The antibodies provided herein may be used, inter alia, for therapeutic cancer applications, including, in some embodiments, treatment of multiple cancer types, which may include acute myeloid leukemia (AML), lymphoblastic leukemia (ALL), lung cancer, breast cancer, pancreatic cancer, ovarian cancer, colorectal cancer, renal cancer, or glioblastoma.

The invention provides a medicine for targeting early-stage precursor T cell acute lymphocytic leukemia (ETP-ALL) and application of the medicine. Dichloroacetic acid (DCA) is used for regulating mitochondrial oxidative phosphorylation, so that electron transport chain flux can be enhanced, ROS (reactive oxygen species) generation can be promoted, endoplasmic reticulum stress related pathways can be activated, the proliferation states of an ETP-ALL leukemia cell line and a primary patient sample can be influenced, and cell apoptosis can be induced. In cell line-derived and patient-derived xenograft models, DCA treatment can reduce leukemia load in bone marrow, spleen and peripheral blood and affect tumor formation characteristics. DCA shows good tolerance in normal hematopoietic system and other leukemia models. The method provides a treatment strategy based on metabolism targeted regulation, and provides a potential technical route and application reference for ETP-ALL research and drug development.

The invention discloses a layered screening method for acute lymphocytic leukemia patients based on methotrexate medication and application thereof, and the layered screening method for acute lymphocytic leukemia is characterized in that the patients are divided into three types of GG, AG and AA by detecting the genotype of the rs1544105 site of an FPGS gene in an in-vitro sample. Based on Meta analysis data of 1760 patients in 11 studies, the GG type is judged as a methotrexate standard dose suitable crowd, the AG or AA type needs to be adjusted, and the AG type corresponds to gt; 20 mg / m < 2 > high-dose methotrexate preparation and AA type corresponding non-folic acid medicine preparation. The invention also includes monitoring somatic mutation in recurrent patients, and switching to a non-methotrexate regimen if GG type mutation is AG / AA type. According to the method, precise layering is achieved, the disease progress risk is reduced, and technical support is provided for pharmaceutical enterprises to prepare personalized drugs and clinical test layering.

The present disclosure provides anti-CD180 binding molecules and uses thereof. In one embodiment, the anti-CD180 binding molecule is an anti-CD180 antibody. Also provided is an anti-CD180 antibody-drug conjugate (ADC) comprising a monoclonal antibody or antigen-binding fragment thereof that targets CD180-highly expressing tumors, a cytotoxic drug payload, and a linker moiety that conjugates the antibody or antigen-binding fragment thereof that targets CD180-highly expressing tumors to the cytotoxic drug payload. The anti-CD180 antibody or antigen-binding fragment thereof, and the ADC comprising the anti-CD180 antibody or antigen-binding fragment thereof, are useful in treating diseases such as acute myeloid leukemia, mantle cell lymphoma, multiple myeloma, follicular lymphoma, acute B-lymphoblastic leukemia, or diffuse large B-cell lymphoma.

The invention belongs to the technical field of biological medicine, and discloses a CCR9-targeted chimeric antigen receptor and application thereof, the chimeric antigen receptor comprises an antigen binding structural domain, a hinge region, a transmembrane structural domain, a co-stimulation structural domain and a signal transduction structural domain which are connected in sequence from N terminal to C terminal; wherein the C end of the signal transduction structural domain is further connected with a CXCR4 chemotactic factor receptor structural domain, and the amino acid sequence of the CXCR4 chemotactic factor receptor structural domain is as shown in SEQ ID NO. 2; the antigen binding structural domain is an anti-CCR9 single-chain variable fragment, and the amino acid sequence of the anti-CCR9 single-chain variable fragment is as shown in SEQ ID NO. 1. The CAR enables immune cells expressing the CAR to obtain stronger tissue chemotactic ability and in-vivo distribution breadth through the energization of CXCR4, and particularly, the ability of the CAR to migrate to bone marrow is remarkably improved, so that the CAR is more beneficial to treatment of acute T lymphocytic leukemia.

The application belongs to the field of organic synthesis and medicinal chemistry, and particularly relates to a kind of indole carbazole glycoside alkaloids and a preparation method and application in anti-leukemia drugs thereof.The indole carbazole glycoside alkaloids or pharmaceutically acceptable salt thereof, structure as shown in formula 1-4:Pharmacological test proves that the indole carbazole glycoside alkaloids shown in formula 1-4 have anti-leukemia activity, and can be used for preparing anti-myelocytic leukemia, anti-myelomonocytic leukemia, anti-lymphocyte leukemia drugs.

Human anti-CD45 antibodies are described. The anti-CD45 antibodies can be engineered into numerous formats, such as antibody-radioisotope conjugates, antibody-immunotoxin conjugates, antibody-drug conjugates (ADCs), antibody-detectable label conjugates, antibody-nanoparticle conjugates, antibody-bead conjugates, multi-domain binding molecules, single chain variable fragments (scFv), and recombinant receptors and can be used as research, diagnostic, or therapeutic tools against CD45-related disorders. Examples of CD45 related disorders include cancers (solid tumors and hematologic malignancies such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)), infections, autoimmune disorders, and metabolic disorders, among other disorders described herein.

A preparation method for and a use of a chimeric antigen receptor (CAR)-γδT cell for immunotherapy of T cell acute lymphoblastic leukemia, relating to the field of biomedicine. The provided anti-CD5 nanobody can specifically bind to a CD5 antigen, and has good affinity. By using the anti-CD5 nanobody as an antigen-binding domain to construct a CAR, the prepared CAR-γδT cell exhibits significant killing activity against CD5-positive tumor cell lines, such as T cell acute lymphoblastic leukemia cells.

This invention discloses a novel use of androstrol-4,6,8(9),13(14)-tetraen-3,11,16-trione, namely its application as a fluorescence imaging reagent. The androstrol-4,6,8(9),13(14)-tetraen-3,11,16-trione solution was co-incubated with human epidermal cells (HaCat) and acute lymphoblastic leukemia cells (BALL-1), respectively, achieving real-time, high-resolution fluorescence imaging of normal and tumor cells. This invention also achieved rapid, real-time in vivo fluorescence imaging in Balb / c nude mice. The compound of this invention is an androstrol natural product derived from *Smilax china*. Its application in cell fluorescence imaging, bioanalysis, and other fields has advantages such as rapid and sensitive cell staining, low cytotoxicity, strong fluorescence signal, and in vivo imaging capabilities, demonstrating practical application value.

The application discloses a novel IRAK4 inhibitor compound shown in formula (I) and use of the compound for preventing or treating IRAK4-mediated diseases, which include but are not limited to rheumatoid arthritis, lupus erythematosus and other autoimmune diseases, activated B-cell-like diffuse large B-cell lymphoma, chronic lymphocytic leukemia, relapsed non-Hodgkin's lymphoma and other lymphomas.

The present invention provides pharmaceutical compositions and methods of use of bisbenzylisoquinoline, e.g., 6,6',7,12-tetramethoxy-2,2'-dimethyl-berbaman, and analogs, derivatives, isomers, and modified forms of the compound, e.g., in crystalline, salt, or salt form, in combination with pharmaceutically acceptable acids or other agents, for the treatment of acute, chronic, and preleukemic conditions, as well as lymphoma and solid tumors. These include, but are not limited to, preneoplastic and neoplastic diseases and solid tumors, such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), atypical chronic myeloid leukemia (aCML), and acute myeloid leukemia (AML), polycythemia vera (PV), chronic lymphoblastic leukemia (CLL), myeloproliferative syndrome (MPS), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), myelofibrosis (MF), and polycythemia vera (PV).

A humanized antibody specifically recognizing human CA IX, and to therapeutic and diagnostic methods utilizing this antibody is disclosed. The methods relate in particular to treatment or diagnosis of cancers selected from squamous cell carcinoma, myeloma, small-cell lung cancer, non-small cell lung cancer, glioma, hodgkin's lymphoma, non-hodgkin's lymphoma, acute myeloid leukemia, multiple myeloma, gastrointestinal (tract) cancer, renal cancer, ovarian cancer, liver cancer, lymphoblastic leukemia, lymphocytic leukemia, colorectal cancer, endometrial cancer, kidney cancer, prostate cancer, thyroid cancer, melanoma, chondrosarcoma, neuroblastoma, pancreatic cancer, glioblastoma multiforme, cervical cancer, brain cancer, stomach cancer, bladder cancer, hepatoma, breast cancer, colon carcinoma, mesothelioma, and head and neck cancer.

The present invention provides novel compounds of Formula (I), (II), or (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and / or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK7, CDK12, or CDK13), and therefore, induce cellular apoptosis and / or inhibit transcription in the subject.

The present disclosure relates to a method of identifying a subject having chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), small lymphocytic lymphoma (SLL), or acute lymphoblastic leukemia (ALL) who will respond to treatment with an anti-CD 19 antibody, the method comprising: a) providing a blood sample obtained from the subject prior to treatment with the anti-CD 19 antibody, b) determining the level of at least one biomarker selected from the group consisting of i) peripheral NK cell count and ii) CD 16 expression level on peripheral NK cells in the sample, c) comparing the level of the at least one biomarker in the sample to a predetermined cutoff level, wherein a level of the at least one biomarker that is equal to or higher than the predetermined cutoff level indicates that the subject will benefit from anti-CD 19 antibody treatment. The present disclosure also relates to a method of treating a patient according to the above screening method and use of an anti-CD 19 antibody to treat such a subject.

The present disclosure relates to CD19 CAR-T cell products and methods of treating recurrent or refractory CD19 + hematological malignancies.

This invention relates to anti-CD103 antibodies and their use in the diagnosis, prognosis, monitoring, and treatment of diseases. An imaging agent comprising the anti-CD103 antibody and a detectable label is also disclosed, wherein the antibody does not block CD103 binding to E-cadherin or at least partially blocks CD103 binding to E-cadherin. Treatment methods involve administering the anti-CD103 antibody, optionally conjugated to a cytotoxic agent. Diseases that need to be treated include, for example, hairy cell leukemia, HCLv, intestinal and extraintestinal lymphoma, enteropathy-associated T-cell lymphoma (EATL), T-lymphoblastic leukemia / lymphoma (T-ALL), T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia / lymphoma (ATLL), mycosis fungoides (ME), anaplastic large cell lymphoma ALCL, cutaneous T-cell lymphoma (CTCL), Cezari syndrome (SS), Alzheimer's disease, Parkinson's disease, or multiple sclerosis.

The present invention relates to immune cells co-expressing a chimeric antigen receptor comprising an OX40 ligand as an intracellular signaling domain and IL-15, and a composition for preventing or treating cancer comprising the same as an active ingredient. The immune cells of the present invention not only exhibit synergistic tumor cell-killing activity by co-expression of the chimeric antigen receptor and IL-15, but also have significantly improved viability and in vitro proliferation rate, and thus they may be used as an efficient anticancer cell therapy. In particular, the immune cells of the present invention, when expressing a chimeric antigen receptor targeting CD5, may be applied as an effective therapeutic composition for various CD5-positive tumors, including lymphocytic leukemia.