35 results about "Hematologic malignancy" patented technology

The invention relates to the field of gene editing and tumor immunotherapy, and discloses a CEACAM1 gene defect type engineered immune cell as well as a preparation method and application thereof. The engineering immune cell is characterized in that: (i) a CEACAM1 gene is knocked out; (ii) specifically recognizing and killing tumor cells expressing CD19; (iii) expressing CAR (chimeric antigen receptor); and iv) the immune cells are T cells. The CEACAM1 gene knockout CAR-T cell prepared by the invention shows an anti-tumor curative effect superior to that of a control group in malignant tumors of a blood system, has stronger in-vivo amplification capacity and good safety, reverses functional inhibition caused by IFN-I to a certain extent, and shows relatively high clinical application potential.

We provide compositions and methods to enhance the anti-cancer specificity of chimeric antigen receptor natural killer cells (CAR-NK) by activating them against cancer antigens while inhibiting them against human leukocyte antigen DR (HLA-DR). HLA-DR is reportedly lost or downregulated in a substantial proportion of hematologic malignancies. An anti-HLA-DR inhibitory CAR (iCAR) is provided to effectively suppress NK cell activation against HLA-DR-expressing cells. Dual CAR-NK cells, which co-express the anti-CD19 or anti-CD33 activating CAR and the anti-HLA-DR iCAR, can preferentially target HLA-DR-negative cells over HLA-DR-positive cells in vitro. The HLA-DR-mediated inhibition is positively correlated with both iCAR and HLA-DR densities. Surrounding cells that express HLA-DR do not affect the target selectivity of the dual CAR-NK cells. We have confirmed that HLA-DR-positive cells are resistant to dual CAR-NK cell-mediated killing in a xenograft mouse model. This can be used for enhancing CAR-NK and CAR-T cell specificity against malignancies with HLA-DR loss.

This invention belongs to the field of biomedical technology, specifically relating to a culture reagent composition and method for organoids from hematologic malignancies. The invention first provides a reagent composition for culturing organoids from hematologic malignancies, including acute lymphoblastic leukemia or acute myeloid leukemia; the reagent composition includes a bone marrow microenvironment mimicking matrix reagent and a specific culture medium. Using the reagent composition of this invention, hematologic malignancies can be cultured efficiently with high survival rates. Furthermore, the bone marrow microenvironment mimicking matrix component used in this invention, compared to the commonly used Matrigel matrix in the field, allows for more accurate phenotypic differentiation of hematologic malignancies.

Disclosed in the present invention are a PIM kinase inhibitor as shown in general formula II, a pharmaceutical composition thereof, a preparation method therefor and the use thereof in the preparation of a drug for preventing and / or treating indications related to a PIM signaling pathway. The compound of the present invention is an ideal PIM kinase inhibitor with a high activity, which can be used for treating and / or preventing diseases including autoimmune diseases and tumors, e.g., inflammatory bowel disease, hematologic malignancies such as acute myeloid leukemia, myelofibrosis and chronic lymphocytic leukemia, and solid tumors such as gastric cancer and prostate cancer.

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for preventing or treating myelodysplastic syndrome and related complications thereof. The traditional Chinese medicine composition comprises sculellaria barbata, astragalus membranaceus, angelica sinensis, nightshade, radix curcumae, red ginseng, duchesnea indica, saussurea involucrata, cyclea verticillata and salvia miltiorrhiza. The traditional Chinese medicine composition has a good prevention and treatment effect on myelodysplastic syndrome and related complications thereof, can effectively inhibit proliferation of hematological tumor cells, and also can inhibit proliferation of the myelodysplastic syndrome by increasing the hemoglobin level, reducing the inflammatory cytokine level and reducing the proportion of peripheral blood T cells. Anemia, inflammation and low immune function caused by the myelodysplastic syndrome can be treated. The invention provides an effective strategy for prevention or treatment of myelodysplastic syndrome and related complications thereof, and provides a new direction for application of the traditional Chinese medicine composition.

Novel bispecific heterodimeric immunoglobulins that target both a component of the human CD47 antigen and human CD38 antigen are provided and in particular those comprising an anti-CD38 heavy chain variable region and a light chain variable region and an anti-CD47 heavy chain variable region and a light chain variable region. The present invention also relates to the use of this 5 novel class of bispecific heterodimeric immunoglobulins to treat autoimmune and proliferative diseases and in particular cancers such as hematologic malignancies and solid tumors.

Provided herein, at least in part, are methods of treating a hematologic malignancy in a human subject in need thereof, comprising orally administering to the subject duvelisib or a pharmaceutically acceptable form thereof.

The invention discloses a blood system tumor drug use guidance system capable of timely discovering skin injury. The system comprises a data acquisition module, a database module, an analysis processing module, an early warning module and an output module, according to the invention, by timely finding and intervening skin injury and optimizing the medication scheme, the injury of the medicine to the body of the patient can be reduced, the treatment effect of the patient is improved, and meanwhile, the life quality of the patient is improved.

Disclosed herein are compositions and methods for deploying interventional agents into constrained biological states using non-crystalline amorphous iron oxide nanoparticles (NAIONPs). The NAIONPs comprise coordination-stabilized, aqueous colloidal dispersions lacking long-range crystalline order and presenting surface-accessible coordination sites for reversible or covalent association with one or more interventional agents. The compositions are configured to modify the biological context in which an interventional agent is presented, enabling functional engagement of agents whose deployment is limited when administered in isolation due to factors including impaired biodistribution, reduced stability, stress sensitivity, immune-mediated clearance, altered cellular responsiveness, or non-optimal exposure conditions. Interventional agents may include polynucleotides, peptides, proteins, small molecules, targeting moieties, radiologic agents, or combinations thereof. The disclosed compositions and methods are applicable to in vivo, ex vivo, and in vitro biological systems, including oncologic disease states such as primary tumors, metastatic disease, hematologic malignancies, and treatment-refractory cancers.

This invention relates to an immunotoxin targeting hematologic malignancies and its application. The immunotoxin comprises a toxic molecule and a carrier. The toxic molecule is pumpkin protein or a mutant of pumpkin protein. The carrier contains an antibody, ligand, or polypeptide capable of binding to hematologic malignancies cells. The antibody comprises an antibody fragment or a small molecule antibody. This invention provides an immunotoxin targeting hematologic malignancies for the treatment of these malignancies. The immunotoxin using a pumpkin protein mutant as the toxic molecule exhibits enhanced specificity against hematologic malignancies cells with high target expression, significantly increased activity in killing target cells, and allows for a substantial reduction in dosage and toxicity. In summary, the immunotoxin targeting hematologic malignancies using a pumpkin protein mutant as the toxic molecule offers advantages in both synergistic effect and reduced toxicity, and has broad application prospects.

The invention discloses a compound or pharmaceutically acceptable salt thereof as well as a preparation method and application thereof. The invention further discloses 22 compounds of the type and a chemical synthesis method thereof, the synthesis route is simple, operation and implementation are easy, and needed reagents are easy to purchase. The novel DIQ01 and the derivative thereof found in the invention can be specifically combined with a target protein KHSRP and inhibit the function of the target protein KHSRP, and the structure type is novel; compared with a plurality of clinical drugs, the compound shows better tumor anti-proliferation activity, and has good tumor selectivity and a wide treatment window. The compound and the pharmaceutical composition thereof can be used for preparing medicines for treating various tumors, and are preferably used for preventing or treating solid tumors such as colorectal cancer, breast cancer, lung cancer and the like and hematological malignant tumors.

Chimeric antigen receptor-transduced T cells (CAR-T cells) show significant efficacy on some hematological malignancies. However, the CAR target is limited to a few antigens, which is primarily due to the non-tumor targeted toxicity of CAR-T cells. Although several strategies are proposed to avoid non-tumor targeted toxicity, the majority of which use complex designs including dual gene expression to achieve specificity. In this study, we have shown that switchable CAR immune cells (e.g., CAR-T cells) with tumor-targeting adapters can mitigate non-tumor-targeting toxicity against tumor antigens, due to which conventional CAR immune cells cannot target tumor antigens such as CD40 and CS1. Therefore, the switchable CAR system is a valuable tool for controlling the toxicity of CAR-T cells while keeping the treatment effect so as to realize CAR anti-tumor targeting expansion.

Novel nucleic acid compositions, vector systems, modified cells, and pharmaceutical compositions that encode or express T cell receptor components directed against melanoma-associated antigen (MAGE) are provided herein. These novel components may be used to enhance an immune response in a subject diagnosed with a MAGE associated disease or condition, such as a hematological malignancy or a solid tumor. Associated methods for treating such subjects are also provided herein.

A companion diagnostic method, kit, and integrated system for quantifying expression of Prostaglandin Reductase 1 (PTGR1) in a patient sample are disclosed. When the measured expression equals or exceeds a predetermined threshold, the patient is selected to receive hydroxyurea methylacylfulvene (LP-184) or a related acylfulvene. The invention enables personalized cancer therapy, improves objective response rates, and minimizes unnecessary exposure to ineffective treatment. Also provided are pharmaceutical combinations, uses, and claims for treating PTGR1 -positive solid tumors and hematological malignancies.

This application provides a method and related equipment for constructing a clonal evolution atlas of hematologic malignancies. The method includes acquiring batch sequencing data and extracting a set of complementarity-determining region (CDR) sequences from the batch sequencing data; filtering the CDR sequence set for pseudoclones to obtain a first sequence set; clustering the CDR sequences in the first sequence set based on edit distance to obtain multiple clonal clusters; performing evolutionary co-validation on clonal pairs in the clonal clusters at multiple time points to obtain an evolutionary trend score; filtering the clonal clusters at multiple time points based on the evolutionary trend score to obtain a clonal evolution time series; and constructing a clonal evolution atlas based on the clonal evolution time series. This method can improve the accuracy of the constructed clonal evolution.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.

The present disclosure addresses this need by providing crystalline fine particle forms of 3-AP, methods for preparation and the treatment for solid tumors and hematological malignancies. In certain aspects, the present disclosure provides novel methods of preparing the compound of Formula I thereof, or 3-APs, crystalline fine particle forms of 3-AP, and compositions comprising them. In certain aspects, the present disclosure provides novel crystalline fine particle form of 3-AP which may provide advantages including improved bioavailability and stability relative to other crystalline or amorphous forms. In other aspects, the present disclosure provides oral dosage forms of crystalline fine particle form of 3-AP and excipients with improved stability. In additional aspects, the present disclosure provides novel methods of synthesizing novel crystalline fine particle form of 3-AP, preparing crystalline 3-AP particle delivery systems (PDS), and preparing novel final dosage forms (FDF) of crystalline fine particle 3-AP. In certain aspects, the present disclosure provides novel crystalline forms of fine particle 3-AP which may provide advantages including improved bioavailability and stability relative to other crystalline or amorphous forms.

KLRB1 binding agents (in particular anti-KLRB1-antibodies and antigen binding portion thereof) with increased humanness and compositions thereof, as well as therapeutic methods of using the agents, e.g., for depleting cells or inhibiting cells or activating cells, (in particular, Th17, Th17.1, ex-Th17, Tc17, MAIT, iNKT, peTh2, ILC2, ILC3, NK cells, and / or neoplastic T or NK cells in vivo), for the treatment of autoimmune disease, allergic diseases, transplant rejection, hematologic malignancies, and cancer.

The present disclosure addresses this need by providing crystalline fine particle forms of triapine (3-AP), methods for preparation and the treatment for solid tumors and hematological malignancies. In certain aspects, the present disclosure provides novel methods of preparing the compound of Formula I thereof, or 3-APs, crystalline fine particle forms of 3-AP, and compositions comprising them. In certain aspects, the present disclosure provides novel crystalline fine particle form of 3-AP which may provide advantages including improved bioavailability and stability relative to other crystalline or amorphous forms. In other aspects, the present disclosure provides oral dosage forms of crystalline fine particle form of 3-AP and excipients with improved stability. In additional aspects, the present disclosure provides novel methods of synthesizing novel crystalline fine particle form of 3-AP, preparing crystalline 3-AP particle delivery systems (PDS), and preparing novel final dosage forms (FDF) of crystalline fine particle 3-AP. In certain aspects, the present disclosure provides novel crystalline forms of fine particle 3-AP which may provide advantages including improved bioavailability and stability relative to other crystalline or amorphous forms.

Aspects of this invention are related to the use of N-desmethyl ruboxistaurin and pharmaceutically acceptable formulations thereof to modulate CDK4 / 6 signaling. The invention encompasses methods for administering N-desmethyl ruboxistaurin to subjects in need, particularly those with a history of cancer or currently experiencing breast cancer, liposarcoma, lung cancer, glioblastoma, melanoma, pancreatic cancer, prostate cancer, colon cancer, ovarian cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma, osteosarcoma, germ cell tumors, advanced solid tumors, lymphoma, leukemia and other hematologic malignancies. The disclosed methods extend beyond disease treatment, including supportive care during radiation chemotherapy and prevention of cancer relapse. N-desmethyl ruboxistaurin administration, alone or in combination with other cancer therapies, is effective in modulating CDK4 / 6 signaling while mitigating toxicity associated with other treatments.

The application provides a drug composition for realizing TK1 / TS double-target co-inhibition and application thereof. The creativity is derived from the key mechanism disclosed by the inventors for the first time, that is, thymidine kinase 1 (TK1) and thymidylate synthase (TS) present co-expression up-regulation in the DNA synthesis period. In-vivo experiments show that the tumor inhibition rate of the drug composition is significantly higher than that of any single drug, synergistic effect is realized, and the drug composition can be used for treating solid tumors or hematological malignancies.

Disclosed herein are methods for treating a hematologic malignancy (e.g., acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or acute lymphoblastic leukemia (ALL)), using an anti-Galectin-9 antibody (e.g., G9.2-17(IgG4). In some embodiments, the anti-Galectin-9 antibody is used as a monotherapy.

The present disclosure relates to antibodies and antibody fragment that are specific for IL3, as well as nucleic acids encoding such antibodies and pharmaceutical compositions comprising such antibodies. The antibodies of the present invention are able to block IL-3 activity in target cells and are useful for the prevention and treatment of diseases or malfunctions which are associated with elevated levels of IL3, such as inflammatory diseases, autoimmune diseases, fibrotic diseases, hematologic malignancies and other illnesses.

KLRB1 binding agents (in particular anti-KLRB1-antibodies and antigen binding portion thereof) with increased humanness and compositions thereof, as well as therapeutic methods of using the agents, e.g., for depleting cells or inhibiting cells or activating cells, (in particular, Th17, Th17.1, ex-Th17, Tc17, MAIT, iNKT, peTh2, ILC2, ILC3, NK cells, and / or neoplastic T or NK cells in vivo), for the treatment of autoimmune disease, allergic diseases, transplant rejection, hematologic malignancies, and cancer.

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.

The invention provides antibodies, antibody fragments or antigen-binding fragments, as well as related antibody drug conjugates (ADCs) and chimeric antigen receptors (CARs), that specifically recognize a multiple myeloma cell surface antigen selected from PTPRG, CADM1, ICAM1, and GARS. Also provided in the invention are methods of using such antibodies in various diagnostic and therapeutic applications for hematologic malignancies including multiple myeloma and acute myeloid leukemia (AML).

The present disclosure relates to compounds that are capable of inhibiting creatine kinase. The present disclosure also relates to methods of treating cancer, such as hematological malignancies.

The invention relates to a modified mononuclear cell / macrophage expressing a chimeric antigen receptor and application of the modified mononuclear cell / macrophage. The present invention includes methods and compositions for the treatment of cancer, whether a solid tumor or a hematological malignancy. By expressing chimeric antigen receptors in monocytes, macrophages or dendritic cells, the modified cells are recruited to the tumor microenvironment where they act as effective immune effectors by infiltrating the tumor and killing the target cells. One aspect includes modified cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treatment of diseases or conditions associated with immunosuppression.