26 results about "Haematological malignancy" patented technology

The invention belongs to the technical field of biological medicine, and discloses an anti-BCMA antibody or an antigen binding fragment thereof as well as a preparation method and application thereof. The amino acid sequences of the heavy chain variable regions CDR1-3 of the anti-BCMA antibody or the antigen binding fragment thereof provided by the invention are respectively shown as SEQ ID NO: 2-4, and the amino acid sequences of the light chain variable regions CDR1-3 are respectively shown as SEQ ID NO: 6-8. The anti-BCMA antibody or the antigen binding fragment thereof has excellent affinity for the BCMA protein, especially an extracellular fragment, can specifically recognize and bind the BCMA protein well, and can be used as a detection antibody of the BCMA protein to realize non-diagnostic purpose detection of the BCMA; meanwhile, the anti-BCMA antibody or the antigen binding fragment thereof can also effectively kill tumor cells overexpressing BCMA, such as pfeffer cells, through complement-dependent cytotoxicity, the cell killing rate is up to 99%, and the anti-BCMA antibody or the antigen binding fragment thereof can be used as an inhibitor of abnormal bone marrow cells overexpressing BCMA protein, is a very potential active ingredient for resisting malignant tumors of a blood system, and has broad application prospects. Good application prospects are realized.

The invention relates to a heterocyclic compound and application thereof.The structure of the heterocyclic compound is shown as a formula (I) or a formula (II), experiments prove that the heterocyclic compound can efficiently degrade CK1alpha through a molecular glue mechanism, so that a p53 pathway, a Wnt / beta-catenin pathway, an ATM pathway and the like are affected, and the heterocyclic compound can be used for preventing or treating diseases caused by abnormally high expression of CK1alpha, and can be used for treating diseases such as diseases caused by abnormally high expression of CK1alpha. The compound can be used for preparing medicines for treating malignant tumors and solid tumors of a blood system, especially medicines for treating acute myeloid leukemia.

Described herein are methods of treating malignancies such as tumors or cancers by orally administering lyophilized compositions comprising arsenic to a subject in need thereof. Malignancies include various hematological malignancies, such as acute myeloid leukemia (AML) including acute promyelocytic leukemia (APL), myelodysplastic syndrome (MDS), multiple myeloma (MM) and lymphomas, and solid tumors including glioblastoma multiforme and breast cancer. Also described herein are oral pharmaceutical formulations comprising lyophilized compositions comprising arsenic and methods for lyophilizing arsenic trioxide, preparing the oral formulation comprising lyophilized compositions comprising arsenic, and treating a subject with malignancies using the oral formulation.

The invention relates to the field of preparation of CD19 targeted CAR-T cells, in particular to an adjustable CD19 targeted CAR-T cell preparation technology which comprises the following operation steps: S1, T cell collection and separation: S1.1, peripheral blood collection: blood is collected from peripheral veins of a patient, and the general collection amount is determined according to the physical condition of the patient and the amount required by subsequent cell culture and is usually between 50ml and 500ml; s1.2, performing density gradient centrifugal separation on the T cells; s2, CAR gene construction and carrier preparation: S2.1, CAR structure design (taking an inducible promoter system as an example), CD19 targeting CAR-T cells can accurately recognize and combine CD19 antigens on the surfaces of tumor cells, and as CD19 is highly expressed on the surfaces of most blood system malignant tumor cells such as B cell lymphoma and leukemia and is limited in expression in normal tissue cells, the CD19 targeting CAR-T cells can be used for accurately recognizing and combining the CD19 antigens on the surfaces of the tumor cells. Therefore, the CAR-T cells can specifically attack tumor cells like a'biological missile ', and damage to normal tissues is reduced.

In certain embodiments, this disclosure relates to method of treating and diagnosing cancer by administering a Bcl-2 inhibitor optionally in combination with a mitochondrial complex II inhibitor. In certain embodiments, a subject is diagnosed with, exhibiting symptoms of, or at risk of cancer wherein the cancer is a hematological malignancy such as multiple myeloma, leukemia, or lymphoma.

The present disclosure relates to CD19 / 22 CAR T-cell products and methods for treating high risk or relapsed CD19+ or CD22+ haematological malignancies.

The invention belongs to the technical field of biological medicines, and particularly relates to a culture reagent composition and a culture method for a malignant tumor organ of a blood system. The invention firstly provides a reagent composition for culturing a hematological malignant tumor organoid, wherein the hematological malignant tumor comprises acute lymphoblastic leukemia or acute myeloid leukemia; the reagent composition comprises a bone marrow microenvironment simulation matrix reagent and a specific culture medium. By adopting the reagent composition provided by the invention, the hematoma organs can be efficiently cultured, and the survival rate is high. And compared with Matrigel matrigel commonly used in the field, the bone marrow microenvironment simulation matrix component adopted by the invention enables phenotypic differentiation of hematoma organs to be more accurate.

The present application relates to a kind of heterocyclic compounds and its application, the structure of the heterocyclic compound is as shown in formula (I) or formula (II), it is proved by experiment that the heterocyclic compounds can be degraded CK1 alpha by molecular glue mechanism, thereby affecting p53 pathway, Wnt / β-catenin pathway and ATM pathway etc., can be used for preventing or treating the disease caused by CK1 alpha abnormal high expression, can be used for preparing the drug for treating hematological malignancies and solid tumor, especially for preparing the drug for treating acute myeloid leukemia.

The present invention provides stable pharmaceutical compositions of pegylated carfilzomib compounds, methods for preparing the compositions, and uses of the compositions for treating cancer, including hematologic malignancies such as multiple myeloma. The compositions can be stored in frozen form or lyophilized to dry solid form.

Novel nucleic acid compositions, vectors, modified cells and pharmaceutical compositions are provided that are useful for treating or preventing a relapse of a haematological malignancy after allogeneic stem cell transplantation (allo-SCT) in a HLA-A*0201 positive human subject. Corresponding methods and uses are also provided.

The present invention relates to antibodies against SIRPα that are suitable for use in anti-cancer therapy. The invention further relates to the use of the anti-SIRPα antibodies in the treatment of human solid tumours and haematological malignancies, optionally in combination with other anti-cancer therapeutics.

Extranodal natural killer / T-cell lymphoma (ENKTCL) is an aggressive haematological malignancy. The treatment of ENKTCL is dependent on the extent of the tumor. However the use of L-asparaginase-containing regimens obtained impressive outcomes as induction or salvage treatment for ENKTCL. Although more than 70% of early-stage patients can achieve long-term survival, patients with advanced-stage disease had extremely poor prognosis even after asparaginase-based chemotherapy regimens. There is thus a medical need for improving the treatment of ENKTCL with L-asparaginase. Now the inventors demonstrate the interest of the use of L-asparaginase in combination with a ferroptosis inducer for the treatment of ENKTCL. In particular, combination of APR-246 and Erwinase R has synergistic effects in KHYG-1 cells. The present invention thus relates to the use of a L-asparaginase in combination with a ferroptosis inducer for the treatment of ENKTCL.

To provide novel nucleic acid sequences, vectors, modified cells, peptides, and pharmaceutical compositions which are useful in the treatment of human subjects, having a mutant nucleophosmin (ΔNPM1 or NPM1 mut) positive haematological malignancy.SOLUTION: The present invention provides an isolated nucleic acid sequence encoding (a) a polypeptide comprising a CDR3 of a TCR α chain polypeptide that specifically binds to a peptide selected from a specific group of sequences and / or (b) a polypeptide comprising a CDR3 of a TCR β chain polypeptide that specifically binds to a peptide selected from a specific group of sequences.SELECTED DRAWING: Figure 1

Novel nucleic acid compositions, vector systems, modified cells, isolated peptides, isolated nucleic acid sequences and pharmaceutical compositions that encode or express T cell receptor components directed against haematopoietic-restricted minor histocompatibility antigens (MiHAs) are provided herein. These novel components may be used in the treatment of a subject having a haematological malignancy, particularly after the subject has undergone allogeneic stem cell transplantation (alloSCT). Associated methods for treating such subjects are also provided herein.

In certain embodiments, this disclosure relates to method of treating and diagnosing cancer by administering a Bcl-2 inhibitor optionally in combination with a mitochondrial complex II inhibitor. In certain embodiments, a subject is diagnosed with, exhibiting symptoms of, or at risk of cancer wherein the cancer is a hematological malignancy such as multiple myeloma, leukemia, or lymphoma.

The present disclosure relates to methods for treating blood transfusion-dependent hematological malignancy patients with oxygen reduced blood.

The invention discloses a triptolide peptide conjugate as well as a pharmaceutical composition and application thereof, and successfully designs and synthesizes the triptolide peptide conjugate which shows remarkable tumor cell proliferation inhibition activity. K-1 shows an excellent inhibition effect on a specific solid tumor cell strain; K-1 has particularly outstanding inhibition activity on a hepatoma cell strain HuH-7, a pancreatic cancer cell strain MIA PaCa-2 and a gastric cancer cell strain HGC-27; the compound shows broad-spectrum and high-efficiency anti-tumor characteristics as shown in the formula K-1, K-2 and K-3, and shows excellent inhibitory activity on a hepatoma cell line HepG2, an acute myelogenous leukemia cell line KG-1, a multiple myeloma cell line RPMI-8226 and a pancreatic cancer cell line MIA PaCa-2. The result not only proves the effectiveness of the K-3 on various solid tumors, but also highlights the strong inhibition effect of the K-3 on malignant tumors of a blood system, and shows the prospect of the K-3 as a broad-spectrum anti-tumor candidate drug. And a powerful guarantee is provided for subsequent deep development of potential antitumor candidate drug molecules and final realization of clinical application transformation.

The application discloses a D-A-D type organic small molecule, nanoparticles containing the same, and a preparation method and application thereof. The D-A-D type organic small molecule and the nanoparticles thereof are particularly suitable for precise photothermal treatment and real-time imaging guidance of hematological malignancies such as leukemia, lymphoma and multiple myeloma. The D-A-D type organic small molecule constructs a D-A-D type conjugated structure, realizes near-infrared absorption red shift to 685 nm through enhancing intramolecular charge transfer (ICT) effect, and promotes non-radiative transition by using high excited state reorganization energy (lambda=1.29eV), with a photothermal conversion efficiency of more than 35%. The small molecule does not contain metal and halogen, has a molecular weight of about 878 Da, and has good biocompatibility and metabolic potential. The small molecule is self-assembled into nanoparticles with a particle size of about 130 nm, and has good colloidal stability and passive targeting ability. Meanwhile, the high molar absorption coefficient and high-efficiency photothermal conversion characteristics of the small molecule endow the small molecule with strong photoacoustic imaging capability, and the small molecule can be used for real-time monitoring of drug distribution and realization of 'diagnosis and treatment integration'.

This invention discloses a predictive model for assessing the risk of severe cytokine release syndrome (SCR) in patients with hematologic malignancies after CAR-T cell therapy. The model includes a nomogram and a prognostic risk scoring formula to assess the risk of SCR after CAR-T cell infusion. The biomarkers are the peripheral blood cytokine concentrations during 24-48 hours after CAR-T cell infusion, including five cytokines: CX3CL1, GZMB, IL4, IL6, and PDGFAA. The nomogram in this invention is the first predictive model established applicable to assessing the risk of SCR in patients with leukemia, lymphoma, and multiple myeloma undergoing CAR-T cell therapy. The model is simple, intuitive, and easy to implement, effectively helping clinicians assess the risk of SCR after CAR-T cell therapy, thus providing theoretical guidance for patient monitoring and treatment.

Novel nucleic acid compositions, vector systems, modified cells, isolated peptides, isolated nucleic acid sequences and pharmaceutical compositions that encode or express T cell receptor components directed against haematopoietic-restricted minor histocompatibility antigens (MiHAs) are provided herein. These novel components may be used in the treatment of a subject having a haematological malignancy, particularly after the subject has undergone allogeneic stem cell transplantation (alloSCT). Associated methods for treating such subjects are also provided herein.

Novel nucleic acid sequences, vectors, modified cells, peptides and pharmaceutical compositions are provided that are useful in the treatment of human subjects having a ΔNPM1 positive haematological malignancy. Corresponding methods and uses are also provided.

The invention discloses a chimera derivative for targeted degradation of N-phenylpyrrole formamide protein and application of the chimera derivative. The compound has a compound represented by general formula (I) # imgabs0 #, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The series of compounds can specifically recognize bromodomains of BET family proteins and collect E3 ubiquitin ligase to form a ternary complex, and target proteins are induced to generate ubiquitination degradation. More importantly, the series of compounds can act on BRD2 / 3 / 4 and BRDT subtypes at the same time through a protein degradation mechanism, and the defect that a traditional inhibitor is insufficient in selectivity is overcome. Therefore, the compound has an important application value in preparation of drugs for treating BET abnormal activation related diseases (including hematological malignant tumors and solid tumors), and particularly provides an innovative solution for overcoming the problem of drug resistance of tumors.

Provided herein are novel nucleic acid compositions, vector systems, engineered cells, and pharmaceutical compositions that encode or express T cell receptor components against cancer-associated antigens (e.g., preferentially expressed melanoma antigen (PRAME) and CCCTC-binding factor (CTCFL)). These novel compositions may be used to enhance immune responses in subjects diagnosed with a PRAME-associated disease or condition, such as a hematological malignancy or solid tumor, or a CTCFL-associated disease or condition. Related methods for treating such subjects are also provided herein.

The application discloses YY20394 and ABT199 combination in the application of preparing a drug for treating acute myeloid leukemia. The application firstly finds that YY20394 and ABT199 have a synergistic effect on the treatment of acute myeloid leukemia, and the treatment effect of acute myeloid leukemia with MCL-1 overexpression can be significantly improved by combining YY20394 and ABT199. The application provides a brand-new treatment scheme for the technical field of blood system malignant tumor treatment, and has important scientific significance and clinical application value.

Provided herein are methods and immune biomarkers that identify progression and treatment options for hematological malignancies (e.g., smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), or multiple myeloma (MM)). Also provided are materials and methods for the prognosis, staging, and monitoring of SMM, MGUS, or MM based on the presence of the immune biomarkers in a sample (e.g., a blood sample or a bone marrow sample), as well as methods for monitoring the progression of SMM, MGUS, or MM, determining the efficacy of a therapeutic agent, determining a treatment for SMM, MGUS (e.g., before progression to MM), or MM, and / or treating SMM, MGUS, or MM. The methods provided herein provide several advantages over invasive biopsies.