78 results about "Chronic lymphoblastic leukemia" patented technology

This invention is generally directed to the use of Indazole Compounds for treating or preventing chronic lymphocytic leukemia. The methods comprise the treatment or prevention of chronic lymphocytic leukemia comprising administering an effective amount of an indazole compound, or a pharmaceutically acceptable salt or composition thereof, to a patient in need thereof.

The invention relates to methods for treating and diagnosing hematologic malignancies, Chronic lymphocytic leukemia and Small Lymphocytic Lymphoma in particular, using PD-1 ligands (PD-L1, PD-L2 or anti-PD-1 antibodies).

A molecular classification procedure based on activity levels of modules in protein networks, wherein the proteins are biomarkers for chronic lymphocytic leukemia (CLL), and method for use of the subnetworks to distinguish between patients at low or high risk of progression of their disease.

The invention is directed to a prognostic indicator for CLL patients who have undergone an allogeneic stem cell transplant (SCT). The indicator is based on a method of monitoring levels and changes in levels of correlating clonotypes of the CLLs at successive time points. The prognostic indicator applies to patients who have survived for at least one year from an allogeneic SCT and includes criteria based on the following two measurements: (a) frequency of CLL correlating clonotypes (e.g. in terms of number per 106 clonotypes) in an initial clonotype profile (from peripheral blood), and (b) fold change in such CLL correlating clonotype number between such initial measurement and a successively measured clonotype profile.

Differential Methylation Hybridization (DMH) was used to identify novel methylation markers and methylation profiles for hematopoieetic malignancies, leukemia, lymphomas, etc. (e.g., non-Hodgkin's lymphomas (NHL), small B-cell lymphomas (SBCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma (B-CLL / SLL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), etc.). Particular aspects provide novel biomarkers for NHL and subtypes thereof (e.g., MCL, B-CLL / SLL, FL, DLBCL, etc.), AML, ALL and MM, and further provide non-invasive tests (e.g. blood tests) for lymphomas and leukemias. Additional aspects provide markers for diagnosis, prognosis, monitoring responses to therapies, relapse, etc., and further provide targets and methods for therapeutic demethylating treatments. Further aspects provide cancer staging markers, and expression assays and approaches comprising idealized methylation and / or patterns” (IMP and / or IEP) and fusion of gene rankings.

Provided are isolated and purified preparations of a combination of a light chain antibody gene and a heavy chain antibody gene, where the light chain and heavy chain antibody genes are the same among more than one patient with B cell chronic lymphocytic leukemia (B-CLL). Vectors comprising those genes and cells comprising those vectors are also provided, as are isolated and purified antibodies encoded by the antibody genes. Anti-idiotype antibodies, peptides, and aptamers that bind to the antigen-binding region of an antibody encoded by the antibody genes are additionally provided, as are multimeric molecules comprising multiple binding sites that bind to the antigen-binding region of an antibody encoded by the antibody genes. Methods of determining whether a patient with B cell chronic lymphocytic leukemia (B-CLL) has a form of B-CLL that is susceptible to treatment directed to eliminating idiotype specific B cell receptor-bearing B-CLL cells are also provided, as are methods of following the progression of treatment of B-CLL in the patient. Additionally, methods of treating a patient having B-CLL are provided, as are methods of identifying a therapeutic agent for B-CLL.

The present invention provides a BTK inhibitor compound (having s structure represented by a formula (I)) and uses of the BTK inhibitor compound in medicines. According to the present invention, the compound and the pharmaceutical composition can be used for treatment of diffuse large B-cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia. The formula (I) is defined in the specification.

The present invention relates to methods and kits for detecting several polynucleotide sequence found to be indicative of a poor prognosis of B-CLL. All the polynucleotides are transcribed from a region on human chromosome 12p21-22. Most of the polynucleotides do not encode larger polypeptides, but may encode small peptides, they may function as RNAs. Four polynucleotides encode a novel protein, which in one preferred embodiment can be used as a cytokine, preferably as an interleulkin. Furthermore the invention relates to methods and compositions for treating B-CLL in particular poor prognosis B-CLL.

The present invention relates to a cell line of lymphocytes comprising γδ T cells, composition and production method thereof, and medical use namely for the use in medicine, namely in cancer immunotherapy.The cell line comprise a sample of human peripheral blood Vδ1+γδ T cells expressing functional natural cytotoxicity receptors (NCRs). These Vδ1+ NCR+ T lymphocytes can directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells.The present invention shows that human Vδ1+ NCR+ T cells can be differentiated and expanded from total γδ peripheral blood lymphocytes (PBLs), upon regular in vitro or ex vivo stimulation with γδTCR agonists and γc-family cytokines. This subset surprisingly expresses NKp30, NKp44 and NKp46, and high levels of Granzyme B that associate with highly enhanced cytotoxicity against lymphoid leukemias.

The invention relates to methods for treating and diagnosing hematologic malignancies, Chronic lymphocytic leukemia and Small Lymphocytic Lymphoma in particular, using PD-1 ligands (PD-L1, PD-L2, or anti-PD-1 antibodies).

The present invention is related to the branch of immunology and particularly with the generation of pharmaceutical compositions comprising a humanized monoclonal antibody recognizing the leukocyte differentiation antigen CD6. Accordingly with that statement, the purpose of this invention is to provide pharmaceutical compositions comprising a humanized anti-CD6 monoclonal antibody for the diagnosis and treatment of Lymphoproliferative Syndromes and particularly the B-Cell Chronic Lymphocytic Leukemia. The essence of the invention consist in the application of a humanized Monoclonal Antibody that recognizes the CD6 antigen, the generation of pharmaceutical compositions comprising that antibody being able to induce apoptosis of malignant cells from B-Cell Chronic Lymphocytic Leukemia patients, reaching a clinical and a histological antitumor efficacy. The field of application of the present invention extends to the Oncology.

The present invention is related to the branch of immunology and particularly with the generation of pharmaceutical compositions comprising a humanized monoclonal antibody recognizing the leukocyte differentiation antigen CD6. Accordingly with that statement, the purpose of this invention is to provide pharmaceutical compositions comprising a humanized anti-CD6 monoclonal antibody for the diagnosis and treatment of Lymphoproliferative Syndromes and particularly the B-Cell Chronic Lymphocytic Leukemia. The essence of the invention consist in the application of a humanized Monoclonal Antibody that recognizes the CD6 antigen, the generation of pharmaceutical compositions comprising that antibody being able to induce apoptosis of malignant cells from B-Cell Chronic Lymphocytic Leukemia patients, reaching a clinical and a histological antitumor efficacy. The field of application of the present invention extends to the Oncology.

A method of identifying a subject having chronic lymphocytic leukemia (CLL) who is likely to be responsive to a treatment compound, comprising obtaining a first sample and a second sample from the subject having CLL; administering 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (Compound A) to the first sample and administering lenalidomide to the second sample; determining the level of a biomarker in the first sample and determining the level of the biomarker in the second sample; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the first sample is different from the level of the biomarker in the second sample.

Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.

The invention provides a BTK (bruton tyrosine kinase) inhibitor compound (compound shown as a formula (I)) and a purpose of the BTK inhibitor compound in medicine. The compound provided by the invention and a medicine composition of the compound can be used for treating diffuse large B cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia.

The level of the leukemic lymphocytes in patients suffering from chronic lymphocytic leukemia (CLL) is reduced by the administration of certain indole or carbazole compounds, such as the nonsteroidal anti-inflammatory drug etodolac or related indole or carbazole compounds.

The invention discloses a coumaronochromones compound as shown by a formula 1. Pharmacological experiments show that the coumaronochromones compound has significant inhibitory action on the proliferation of B lymphocytes and T lymphocytes, and can be used for preparing immunosuppressive agents or medicaments for treating various immunologic diseases such as rheumatoid arthritis, lupus erythematosus and the like, and the medicaments for treating B cell type chronic lymphocytic leukemia. The invention also provides a preparation method.

Disclosed are histone deacetylase (HDAC) inhibitors, or combinations comprising an HDAC inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of chronic lymphocytic leukemia in a subject in need thereof. Also provided herein are methods for treating chronic lymphocytic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an HDAC inhibitor, or a combination comprising an HDAC inhibitor and a BTK inhibitor. Other related methods are disclosed.

The invention relates to methods of treating B-cell chronic lymphocytic leukemia, and other CD23+ malignancies, in patients with poor prognostic markers. The method comprises administration of an CD23 antibody, including for example, lumiliximab to a mammal that over expresses a poor prognostic marker. The method can also comprise administration of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab. Patients with poor prognostic markers include, for example, patients that overexpress ZAP70, CD38, β2-microglobulin and / or soluble CD23.

The invention relates to a combined reagent and a system for evaluating chronic lymphocytic leukemia prognosis, and belongs to the field of medical technology detection. The combined reagent comprisesat least one of the following antibody combinations: an antibody combination 1 including CD5, IgG1, CD3, CD 19 and CD45 antibodies, an antibody combination 2 including CD5, ZAP70, CD3, CD19 and CD45antibodies, and an antibody combination 3 including CD38, CD49d, CD19, CD5 and CD45 antibodies. In the above antibody combinations which aim at CLL (Chronic Lymphocytic Leukemia), the expression of ZAP70, CD38 and CD49d has a great value on an aspect of prognosis evaluation, ZAP70 is accurate, bus since an intracellular dyeing and gating technology restricts clinical application, and the combinedreagent solves the problem to a maximum degree. In addition, two indexes are increased, markers are combined, and chronic lymphocytic leukemia prognosis can be more comprehensively evaluated.

The invention discloses a chronic lymphocytic leukemia tumor cell recognition method based on machine learning. The method comprises the following steps: (1) detecting an antigen related to chronic lymphocytic leukemia, and calculating a confidence interval boundary of fluorescence intensity of the antigen; (2) constructing a neural network model, wherein model input is a confidence interval boundary, and the model output is expected output for judging whether chronic lymphocytic leukemia exists or not; (3) training the neural network model by utilizing the collected cell fluorescence intensity data of the chronic lymphocytic leukemia patient and the non-chronic lymphocytic leukemia patient; and (4) collecting cell fluorescence intensity data of a new patient needing to be diagnosed, and giving a reference recognition result by utilizing the neural network model. The clinician can be assisted in accurately identifying whether the tumor cells belong to chronic lymphocytic leukemia tumorcells or not by means of machine learning and a large amount of historical data, and thus the efficiency and the quality of clinical diagnosis are improved.

The invention features compositions and methods for diagnosing and treating chronic lymphocytic leukemia (CLL) based upon the absence or presence of a lesion, e.g., a deletion, at chromosome 14q32.33.

The present disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a Bruton's tyrosine kinase (BTK) inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia.

The invention provides an ApoA-based chronic lymphocytic leukemia prognosis risk assessment system and application thereof, and belongs to the technical field of biological medicine and molecular biology. The prognosis value of ApoA in chronic lymphocytic leukemia is proved, and the inhibition effect of L-4F on a CLL cell line and primary cells is proved in a cell experiment, which can provide a new direction for the treatment of CLL. On the other hand, a new ApoA and ADA-based risk rating system-ARAA risk rating system is established, and the effect of the ARAA risk rating system in evaluating the OS and PFS of the CLL patient is proved. The ARAA risk degree scoring system is superior to Binet grading, and plays a role in optimizing CLL patient risk degree layering, so that the ARAA risk degree scoring system has good practical application value.

The invention disclosed herein is directed to compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (I), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist.

Methods for treating a human with chronic lymphocytic leukemia using a combination of an interleukin-2 and an anti-CD52 antibody are provided. These therapeutic agents are administered as two separate pharmaceutical compositions, one containing an IL-2, the other containing an anti-CD2 antibody, according to a dosing regiment. Administering of these two therapeutic agents together results in a positive therapeutic response that is improved with respect to that observed with anti-CD52 antibody alone.

The invention disclosed herein is directed to compounds of Formula (1a) and (1b) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocyticδ leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (1a) or (1b), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a therapeutically effective amount of a compound which is a dual antagonist of PPARα and PPARδ. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a herapeutically effective amount of a dual antagonist of PPARα and PPARδ.

The invention disclosed herein is directed to compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (I), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and / or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist.

The invention discloses a heteroaryl compound and application thereof, and provides a heteroaryl compound as shown in a formula I, a tautomer, a stereoisomer or a pharmaceutically acceptable salt thereof. The compound has good tumor inhibition activity, especially on human chronic lymphocytic leukemia, lung adenocarcinoma, breast cancer, ovarian cancer, breast cancer or pancreatic cancer, and hasgood inhibitory activity on drug-resistant breast cancer, lung cancer, ovarian cancer or leukemia.