Neoplasia hematologikoak: Leuzemiak, Linfomak eta Mielomak

METHODS OF TREATING LYMPHOMA USING ANTI-TIGIT ANTIBODIES

Resumen de: CN119365214A

Methods of treating diffuse large B-cell lymphoma (DLBCL) or increasing, enhancing, or stimulating an immune response with antibodies and antigen-binding fragments thereof that specifically bind to TIGIT (T cell immune receptors with Ig and ITIM domains) in combination with an anti-PD1 antibody and/or an anti-CD20 antibody are provided.

METHOD FOR ENHANCING EMBRYO IMPLANTATION

Resumen de: US2025121001A1

A method of enhancing embryo implantation in a subject is disclosed which comprises administering to the uterine cavity of the subject a formulation comprising copper and/or zinc in an amount effective to stimulate endometrial production of leukaemia inhibitory factor (LIF) and/or vascular endothelial growth factor (VEGF). Alternatively, a device may be inserted into the uterine cavity of the subject, wherein the device comprises copper and/or zinc, for a period of time that is effective to stimulate endometrial production of LIF and/or VEGF. The method is suitable for use with women undergoing treatment by any of the assisted reproductive technologies, such as those involving the transfer of embryos such as in vitro fertilisation (IVF) and variants including IVF-ICSI (intracytoplasmic sperm injection) and in vitro maturation (IVM) treatments, as well as intrauterine-insemination (IUI) therapy. However, the method is also applicable for women wanting to improve their prospects of pregnancy through natural conception.

METHODS FOR PREDICTING RESPONSIVENESS OF LYMPHOMA TO DRUG AND METHODS FOR TREATING LYMPHOMA

Resumen de: WO2025080543A1

Provided herein are methods of predicting the responsiveness of a lymphoma patient to a cancer treatment. Also provided herein are methods of treating a lymphoma patient based on predicting the responsiveness of the lymphoma patient to a cancer treatment.

METHODS, REAGENTS AND KITS FOR DETECTING MINIMAL/MEASURABLE DISEASE IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Resumen de: WO2025080137A1

The invention relates to the field of leukemia/lymphoma diagnosis, more specifically to the detection of minimal numbers of leukemia/lymphoma cells in chronic lymphocytic leukemia (CLL) patients after therapy has started. Provided is a reagent composition for the cytometric detection of minimal residual disease (MRD) in CLL, the reagent composition comprising a panel of at least six antibodies conjugated to a detectable label, the panel comprising antibodies directed against the markers CD180, CD38, CD81, CD19, CD27 and CD5.

METHODS FOR TREATING MULTIPLE MYELOMA COMPRISING AN ANTI-CD38 ANTIBODY COMBINED WITH BORTEZOMIB, LENALIDOMIDE AND DEXAMETHASONE

Resumen de: WO2025080911A1

The present disclosure is directed to methods of treating multiple myeloma. The present disclosure is directed to methods of treating newly diagnosed multiple myeloma in a subject in need thereof, for example, by subcutaneously administering to the subject a pharmaceutical composition comprising an anti-CD38 antibody in combination with bortezomib, lenalidomide, and dexamethasone.

COMBINATION THERAPY WITH CLK/DYRK INHIBITORS AND BCL2 INHIBITORS TO TREAT LEUKEMIA

Resumen de: WO2025080282A1

The present disclosure provides methods for treating leukemia (e.g., AML) using a CLK/DYRK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor (e.g., venetoclax). Kits for use in practicing the methods are also provided.

COMPOUNDS AND METHODS TO SENSITIZE CANCER CELLS TO CISPLATIN

Resumen de: US2025120947A1

The present invention generally relates to sensitizer compounds and their use to sensitize cancer and/or pre-cancerous cells of certain cancers to treatment with certain resistance-prone therapeutics used in cancer therapy. In embodiments, the conjugates of particular esters or amides of Near Infrared Dyes, are used as sensitizers to avoid or overcome therapeutic resistance once formed. In embodiments, the sensitizers include conjugates with Cisplatin, Simvastatin, Artemisinin, platin-based compounds or statins. In embodiments, the resistance prone cancer therapeutics include cisplatin, gemcitabine, doxorubicin, paclitaxel, docetaxel, and platin-based compounds. These may be administered in combination with the sensitizer, or the sensitizer itself may comprise an therapeutci-derived moiety conjugated to the sensitizer, for example as is the case for dye-CIS conjugated sensitizers. Alternatively, the sensitizer may be co-administered with one or more therapeutic. Embodiments of the invention may advantageously be used in cancers that have a tendency to develop resistance to such cancer therapeutics and/or to form metastases, including e.g. lung, pancreatic, prostate, testicular, ovarian, cervical, bladder, breast, head and neck, esophageal, and stomach, cancers, germ cell tumors, lymphomas and other cancers.

ANTI-HUMAN CD45RC ANTIBODIES AND USES THEREOF

Resumen de: US2025122300A1

Isolated anti-human CD45RC antibodies or binding fragments thereof, nucleic acids and expression vector encoding the same, compositions including the same, and uses thereof as medicaments, including for the prevention and/or treatment of CD45RChigh-related diseases (including autoimmune diseases, undesired immune responses, monogenic diseases, and lymphoma or cancer), in particular for use in preventing and/or treating graft-versus-host disease (GVHD).

Anti-BCMA Antibody Drug Conjugate Combination Treatment for Cancer

Resumen de: US2025122297A1

Disclosed herein is a method of treating cancer, such as multiple myeloma, involving the combination of an anti-BCMA antigen binding protein (e.g., an anti-BCMA antibody) and an immunomodulatory drug (e.g. pomalidomide or lenalidomide). The combinations can also include an anti-inflammatory compound (e.g. dexamethasone).

METHOD OF TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE LEUKEMIA

Resumen de: US2025122295A1

The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

COMBINATION OF PAK1 INHIBITORS AND CLK INHIBITORS FOR PREVENTING RESISTANCE TO CHEMOTHERAPY IN PATIENTS SUFFERING FROM ACUTE MYELOID LEUKEMIA

Resumen de: WO2025078334A1

Chemotherapy resistance is the major therapeutic barrier in acute myeloid leukemia (AML). To address this issue, the inventors generated a syngeneic mouse model of AML, which we evolved to develop resistance to a front-line chemotherapy regimen. The inventors identified SRRM1 as a critical vulnerability of chemoresistant leukemic cells and identified that PAK1 and CLK kinases are regulators of SRRM1 in chemoresistant AML cells. Human and murine chemoresistant cells were found to be markedly more sensitive to inhibitors of PAKs (FRAX597) and CLKs (TG003 and ML 167) compared to their naive counterparts, an effect which was even further enhanced by treatment with cytarabine and daunorubicin. Simultaneous suppression of Clk1 and Pak1 or Clk-4 and Pak1 using validated shRNAs and combinations of FRAX597 and TG003, or FRAX597 and ML 167 synergized to reduce the growth and the colony-forming capacity of chemoresistant AML cells and sensitized them to chemotherapy. The combined treatment improved overall mouse survival and reduced disease burden in the chemoresistant AML mouse models. Moreover, AML patient cells that were primarily refractory or from a post chemotherapy relapse (n=21 ) exhibited a higher ex vivo sensitivity to the FRAX597 + TG003 combination in comparison with chemosensitive patients at diagnosis (n=28). Finally, combined PAK1 and CLK inhibition more effectively reduced disease progression in animals transplanted with the relapse sample than in those engrafted with th

COMPOSITIONS AND METHODS FOR TREATING CD20 POSITIVE CENTRAL NERVOUS SYSTEM LYMPHOMAS

Resumen de: WO2025080924A1

Provided herein is a recombinant adeno-associated virus (rAAV) comprising an AAV capsid and an expression cassette comprising an engineered nucleic acid sequence encoding an anti-hCD20 antibody (i.e., rituximab) comprising heavy chain and light chain operably linked to regulatory control sequences which direct expression of rituximab in a target cell. Also provided are a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, nucleic acid molecule, packaging host cells, rAAV production system, and a method of treating CD20-positive central nervous system lymphomas

DYRK/CLK PROTACS AND USES THEREOF

Resumen de: WO2025080753A1

The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) one or more of the following kinases: DYRK1A, DYRK1B, DYRK2, DYRK3, DYRK4, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8/19, PI3K, PDGFrA/B, mTOR, HIPKs, and/or CMGC kinases leading to inhibition of WNT signaling. In particular, the present invention is directed to compounds, which contain on one end an E3 ubiquitin ligase binding moiety which binds to an E3 ubiquitin ligase and on the other end a moiety which binds one or more of the following kinases: DYRK1A, DYRK1B, DYRK2, DYRK3, DYRK4, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8/19, PI3K, PDGFrA/B, mTOR, HIPKs, and/or CMGC kinases leading to inhibition of WNT signaling, such that the one or more kinases is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the one or more kinases. The bifunctional compounds serve as therapeutics for the treatment of Alzheimer's disease, down syndrome, diabetes, an autoimmune disease, an inflammatory disorder (e.g., airway inflammation, osteoarthritis (e.g., knee related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colorectal cancer, acute myeloid leukemia, myelodysplastic syndrome), a viral infection (e.g., SARS-CoV-2 infection (e.g., COVID-19)), and other diseases.

METHODS FOR EVALUATION AND TREATMENT OF TYROSINE KINASE INHIBITOR (TKI)-RESISTANT ACUTE MYELOID LEUKEMIA

Resumen de: US2025123282A1

Disclosed here are methods of evaluating resistance to a tyrosine kinase inhibitor (TKI) therapy of acute myeloid leukemia (AML) in a subject that include detecting the status of CD33, CD44, and phosphorylated BCL2 associated agonist of cell death (pBAD) expression. Also disclosed herein are methods of treating AML in a subject by administering a TKI and one or more inhibitors targeting a TKI-activated compensation pathway to the subject.

COMBINATION THERAPIES FOR TREATMENT OF T-CELL LYMPHOMAS WITH TOLINAPANT, CEDAZURIDINE AND DECITABINE

Resumen de: AU2022476674A1

The present disclosure relates generally to methods of treating T-cell lymphomas with combination therapies.

PROTEASOME INHIBITORS AND METHODS OF USE THEREOF

Resumen de: WO2025080942A1

The present disclosure provides proteasome inhibitors of Formula (I), useful in treating cancer, such as multiple myeloma and mantle cell lymphoma.

ANTI-BCMA SINGLE-DOMAIN ANTIBODY, AND PREPARATION METHOD THEREFOR AND USE THEREOF

Resumen de: WO2025077315A1

Provided are an anti-BCMA single-domain antibody, and a preparation method therefor and the use thereof. Specifically, provided is a single-domain antibody having an amino acid sequence of SEQ ID No. 1. The single-domain antibody has high affinity, can thoroughly specifically target BCMA-positive cells, and can be applied to the detection of BCMA expression in bone marrow cells of MM patients. The single-domain antibody can be prepared into a specific antibody drug clinically used for preventing and treating BCMA-target-related diseases (such as multiple myeloma, B-cell acute lymphoblastic leukemia, non-Hodgkin's lymphoma and Hodgkin's lymphoma); or a BCMA protein detection kit, etc. The single-domain antibody has a stable structure, a small molecular size, is easily recombinantly expressed and has a low production cost, can be used alone or as a drug delivery system to carry relevant drugs, and has very wide prospects and important significance in fields such as drug application and clinical diagnosis.

MULTI-SPECIFIC ANTIBODY TARGETING BCMA, GPRC5D AND T CELLS AND APPLICATION THEREOF

Resumen de: EP4538294A1

The present application relates to a multi-specific binding molecule targeting BCMA, GPRC5D and a T cell receptor. In particular, the present application discloses a multi-specific antibody against BCMA, GPRC5D and CD3, which can bind to a tumor surface antigen while activating T cells, thereby promoting the specific killing of tumor cells, in particular BCMA-positive or GPRC5D-positive multiple myeloma, by T cells. The present application further provides a preparation method for and the application of the multi-specific binding molecule.

BISPECIFIC ANTIBODY AGAINST CD3 AND CD20 IN COMBINATION THERAPY FOR TREATING DIFFUSE LARGE B-CELL LYMPHOMA

Resumen de: US2025115665A1

Provided are methods of clinical treatment of Diffuse Large B-cell Lymphoma (for example, relapsed and/or refractory Diffuse Large B-cell Lymphoma) in human subjects using a bispecific antibody which binds to CD3 and CD20 in combination with lenalidomide or ibrutinib and lenalidomide.

MODULATING THE TUMOR IMMUNE MICROENVIRONMENT VIA TARGETING REGULATORY T CELLS (TREGS) WITH CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY

Resumen de: WO2025076471A2

Disclosed are chimeric antigen receptors that target glycoprotein A repetitions predominant (GARP) and methods of their use in the treatment of cancer including, but not limited to breast cancer, bladder cancer, glioblastoma, or leukemia or other malignancies characterized with GARP+ Tregs.

FOLLICULAR LYMPHOMA TRANSCRIPTOMIC CLASSIFIER

Resumen de: WO2025076428A1

The present disclosure relates to a method for classifying a subject diagnosed with follicular lymphoma (FL) into 7 FL subtypes (FL1-FL7) and related methods of treating a subject diagnosed with FL. The present disclosure further includes related compositions, e.g., isolated probes and primers, as well as kits and arrays comprising same. A therapy guidance software tool is also disclosed.

NOVEL DNA METHYLATION MARKER TAGME-5 FOR TUMOR IDENTIFICATION AND USE THEREOF

Resumen de: WO2025073216A1

Provided are a novel DNA methylation marker TAGMe-5 for tumor identification and a use thereof. The tumor marker TAGMe-5 shows a significant DNA methylation difference in para-carcinoma tissues and carcinoma tissues, the difference has remarkable statistical significance, and the difference is shown in a plurality of tumors such as solid tumors and non-solid tumors. The solid tumors comprise lung cancer, liver cancer, prostate cancer, cervical cancer, endometrial cancer, urothelial carcinoma, a biliary tract tumor, etc. The non-solid tumors comprise a blood system tumor, lymphoma, etc. Therefore, the tumor marker can be used for screening, molecular diagnosis, prognosis, and therapeutic effect evaluation for clinical multi-tumors (Pan-cancer).

HIGH THROUGHPUT PARALLEL SYNTHESIS OF SMALL MOLECULE DEGRADERS

Resumen de: WO2025076501A1

Disclosed herein are high throughput synthetic methods for the deliberate and prospective discovery of molecular glues which can be used to form composite protein-ligand surfaces that facilitate interfacial binding to other proteins over dispersed surfaces. In particular, this application discloses a high throughput approach using sulfur(VI) fluoride exchange (SuFEx) transformations and N-hydroxysuccinimide (NHS)-ester derived amide couplings to prospectively repurpose known ligands for a prolein-of-interest into degraders and compounds capable of inducing proximity to other proteins. Disclosed herein are methods of developing known ligands of a target protein into degraders of the target proteins. Further disclosed are methods of developing novel small molecule chromatin-competitive inhibitors of the eleven nineteen leukemia (ENL) YEATS domain into effective degraders of ENL.

COMBINATION THERAPIES WITH A CELL THERAPY EXPRESSING A GPRC5D-TARGETING CAR AND RELATED METHODS AND USES

Resumen de: WO2025076472A1

Provided herein are methods and uses of combination therapies involving GPRC5D- targeted cell therapy comprising chimeric antigen receptors (CARs), which contain extracellular antigen-binding domains that bind to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D), and a combination agent, e.g. an immunomodulatory compound, for treating subjects with cancers such as multiple myeloma, and related methods, uses, and articles of manufacture.

METHOD TO PREDICT AML OUTCOME

Nº publicación: WO2025068340A1 03/04/2025

Solicitante:

INSTITUT NATIONAL DE LA SANTE ET DE LA RECH MEDICALE [FR]
INST JEAN PAOLI & IRENE CALMETTES [FR]
CENTRE NATIONAL DE LA RECHERCHE SCIENT [FR]
UNIV DAIX MARSEILLE [FR]
INSTITUT NATIONAL DE LA SANT\u00C9 ET DE LA RECHERCHE M\u00C9DICALE,
INSTITUT JEAN PAOLI & IRENE CALMETTES,
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE,
UNIVERSIT\u00C9 D'AIX MARSEILLE