18 results about "Chronic lymphoblastic leukemia" patented technology

The present invention relates to the treatment of subjects having CD20-positive cell proliferative disorders (e.g., B cell proliferative disorders, such as non-Hodgkin's lymphomas or chronic lymphocytic leukemia). More specifically, the invention pertains to the treatment of subjects having a B cell proliferative disorder by subcutaneous administration of mosunetuzumab as a monotherapy or in combination with lenalidomide.

As described below, the present invention features compositions, panels of biomarkers, and methods for selecting a subject with chronic lymphocytic leukemia (CLL) for treatment using an agent and / or for inclusion in a clinical trial using the agent to treat CLL.

The present invention provides ROR1 specific chimeric antigen receptors (CAR) and their therapeutic use. The CAR comprises a signal peptide, a ROR1 antigen binding domain, a hinge, a transmembrane domain, a co-stimulatory domain and an intracellular signaling domain. The modified immune cells endowed with such CARs are suitable for treating malignancies such as cancer, chronic lymphocyte leukemia (CLL), and acute lymphocytic leukemia (ALL).

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.

Provided herein are methods of treating a subject having a CD20 - positive cell-proliferative disorder (e.g., a B-cell proliferative disorder, e.g., non-Hodgkin's lymphoma or chronic lymphocytic leukaemia).SOLUTION: The present invention provides the treatment of a subject having a B-cell proliferative disorder by subcutaneous administration of mosnetuzumab as monotherapy or in combination with lenalidomide.SELECTED DRAWING: Figure 10

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.

The present invention relates to a first composition comprising one of CD4+ T cells and CD8+ T cells for use with a second composition comprising the other of CD4+ T cells and CD8+ T cells in a method for treating a subject having chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), wherein the method comprises administering to the subject a dose of modified T cells comprising CD4+ and CD8+ T cells comprising a chimeric antigen receptor (CAR) that binds specifically to CD19, wherein: (i) the subject has relapsed following remission after treatment with, has become refractory to or has failed treatment with and / or has been intolerant to ibrutinib and venetoclax;(ii) administration comprises administering a plurality of separate compositions, wherein the plurality of separate compositions comprises the first composition comprising one of the CD4+ T cells and CD8+ T cells and the second composition comprising the other of the CD4+ T cells and CD8+ T cells, and (iii) the modified T cell dose comprises a defined ratio of CAR-expressing CD4+ cells to CAR-expressing CD8+ cells, optionally wherein the ratio is between approximately 1:3 and approximately 3:1;

This invention discloses a compound with BTK inhibitory activity, its preparation method, and its application; the compound is shown in Formula I. The compound of this invention can effectively inhibit Bruton's tyrosine kinase and can be used as a targeted drug for the treatment of diseases related to the BTK signaling pathway, such as chronic lymphocytic leukemia, multiple myeloma, mantle cell lymphoma, systemic lupus erythematosus, rheumatoid arthritis, and chronic graft-versus-host disease.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of KRAS to regulation of fatty acid metabolism in chronic lymphocytic leukemia. Specifically, the regulation and control effect and mechanism of KRASG13D mutation on CLL fatty acid oxidation and malignant progression are disclosed for the first time through research, the relationship between KRAS mutation and CLL progression is disclosed from the perspective of energy metabolism, and the KRASG13D mutation activates a downstream PI3K / AKT / mTOR signal channel through up-regulation of PIK3C2A, so that CLL cell fatty acid oxidation and proliferation activity enhancement are promoted. The PI3K inhibitor is applied to treatment of recurrent and refractory CLL, however, the research finds that KRASG13D mutant CLL cells show the drug resistance tendency of the PI3K inhibitor, and the treatment effect of the PI3K inhibitor can be improved by combined application of the KRAS inhibitor, so that a clue is provided for further knowing the occurrence and development mechanism of CLL and developing a new strategy for clinical targeted treatment.

The invention discloses a compound with BTK inhibitory activity and a preparation method and application thereof. The compound is shown as a formula I. The compound can effectively inhibit Bruton's tyrosine kinase, and can be applied to targeted drugs for treating diseases related to BTK signal channels, such as chronic lymphocytic leukemia, multiple myeloma, mantle cell lymphoma, systemic lupus erythematosus, rheumatic arthritis, chronic graft versus host disease and the like.

The present invention relates to compounds of formula (I), processes for their preparation, and pharmaceutical compositions containing them as the active ingredient. Compounds of the present invention may be useful as mitochondrial KV1.3 inhibitors (mitoKV1.3) to treat cancer diseases and the like, including breast, colon, and prostate tumors, melanoma, smooth muscle, and skeletal muscle cancer, chronic lymphocytic leukemia, glioblastoma, and pancreatic ductal adenocarcinoma.

The present invention relates to a method for identifying a subject who has chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), small lymphocytic lymphoma (SLL), or acute lymphoblastic leukemia (ALL) who responds to treatment with an anti-CD19 antibody, said method comprising: a) providing a blood sample obtained from said subject prior to treatment with said anti-CD19 antibody, b) determining the level of at least one biomarker in said sample selected from the group consisting of i) peripheral NK cell count, and ii) CD16 expression levels in peripheral NK cells, c) comparing the level of said at least one biomarker in said sample to a predetermined cutoff level, wherein levels of said at least one biomarker at or above the predetermined cutoff level are indicative of a subject who would benefit from treatment with an anti-CD19 antibody.This disclosure also relates to a method for selecting a patient for treatment in accordance with the above and to the use of an anti-CD19 antibody for the treatment of such patient.

To provide an agent that delivers a glucocorticoid modulator to treat diffuse large B-cell lymphoma (DLBCL), acute lymphoblastic leukemia (ALL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL).SOLUTION: The present invention provides antibody-drug conjugates that target B-cells via an anti-CD19 antibody linked to a glucocorticoid receptor modulator (GRM) agonist payload.SELECTED DRAWING: Figure 1

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).

To provide novel compositions for treatment of multiple myeloma and chronic lymphocytic leukemia using an approach that can exhibit specific and efficacious anti-tumor effect.SOLUTION: The invention provides an isolated nucleic acid molecule encoding a therapeutic payload operably connected to a surface antigen-regulated inducible promoter comprising a nucleotide sequence comprising multiple specific sequences or a combination thereof, and where the surface antigen-regulated inducible promoter adjusts its level of transcription dependent upon the level of expression of the surface antigen on a target cell thereby achieving a T-cell response precisely regulated to the level of the target antigen present in the tumor milieu. Also provided are a vector, a cell, and a pharmaceutical composition.SELECTED DRAWING: Figure 2

The present invention relates to a novel anti-HLA-DR IgM monoclonal antibody and its use alone or in combination with anti-CD20 IgG1 or IgM antibodies in the treatment of lymphoma, and in particular chronic lymphocytic leukemia (CLL). Figure 4B

The present invention belongs to the field of biomedicine and molecular biology technology, and specifically relates to the application of ACLY in regulating lipid metabolism in chronic lymphocytic leukemia and promoting drug sensitivity of PI3K inhibitors. Studies have shown abnormal lipid accumulation in chronic lymphocytic leukemia cells and overexpression of ACLY, a key enzyme for fatty acid synthesis, in chronic lymphocytic leukemia, and serves as a hub for lipids, cholesterol and acetylation in chronic lymphocytic leukemia. At the same time, ACLY can be regulated by the PI3K‑AKT pathway and increase the drug sensitivity of Idelalisib. In summary, the research results of the present invention show that ACLY acts as a hub connecting cell metabolic epigenetics in chronic lymphocytic leukemia, and reveals the molecular mechanism of chronic lymphocytic leukemia cell proliferation, which helps to improve the treatment effect and therefore has good practical application value.