108 results about "Myeloid cells" patented technology

The application relates to fused pyrimidinone derivatives of the general formula (I) which act as agonists of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) useful for the treatment of Parkinson's disease, rheumatoid arthritis, Alzheimer's disease, amyotrophic lateral sclerosis, Nasu-Hakola disease, frontotemporal dementia, multiple sclerosis, prion disease, and stroke.

A method of treating or preventing central nervous system cancer in a subject in need thereof is described. The method includes administering to the subject a therapeutically effective amount of myeloid cells modified to express interleukin-2. A population of genetically engineered myeloid cells (GEMys) comprising bone marrow derived myeloid cells that have been genetically modified to express interleukin-2 is also described.

This document provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as acute myeloid leukemia (AML)). For example, methods and materials for making and / or using T cells expressing (e.g., engineered to express) (a) one or more chimeric antigen receptors (CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more inhibitory CARs (iCARs) having the ability to bind to a class I major histocompatibility complex (MHC) polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, T cells provided herein can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant to target (e.g., target and destroy) the mammal's myeloid cells while sparing the donor-derived myeloid cells.

We have discovered that allogeneic HSC-engineered human iNKT (3rdHSC-iNKT) cells display potent anti-GvHD functions, by eliminating antigen-presenting myeloid cells in vitro and in xenograft models, without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia. The 3rdHSC-iNKT cells closely resembled the CD4−CD8− / + subsets of endogenous human iNKT cells in phenotype and functionality. Embodiments of the invention harness these discoveries in new methods and materials for alleviating graft versus host disease.

The present disclosure provides conjugates of anti-Nectin-4 antibodies or antigen binding fragments thereof to a myeloid cell agonist, compositions comprising the conjugates, and methods of treating cancer with the conjugates. The present disclosure also provides for anti-Nectin-4 antibodies or antigen binding fragments thereof and method for using the antibodies or antigen binding fragments thereof in treating cancer.

The present invention relates to compounds useful for modulating trigger receptor 2 ('TREM2') expressed on myeloid cells. The invention also relates to the use of said compounds in the treatment of conditions associated with loss of TREM2 function, such as neurodegenerative diseases, and to pharmaceutical compositions comprising said compounds.

To provide compounds useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2").SOLUTION: The present invention provides compounds of Formula (I). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).SELECTED DRAWING: None

The invention discloses a method for screening a B-cell lymphoma biomarker, and belongs to the technical field of bioinformatics. The invention aims to provide a more accurate and simple method for screening the B-cell lymphoma biomarker. The invention provides a method for screening a B cell lymphoma biomarker. The relation between the infiltration ratio of all cell subgroups of T / NK and myeloid cells and the lifetime of a patient is screened out by utilizing scRNA-seq data of Burki lymphoma, diffuse large B cell lymphoma, follicular lymphoma and spleen marginal region lymphoma and bulk RNA-seq data of a Burki lymphoma and diffuse large B cell lymphoma database. And a theoretical basis is provided for screening survival analysis of lymphoma diseases.

The present invention relates to compounds of Formula (I) useful for modulating Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2") expressed on myeloid cells. The present invention also relates to the use of the compounds for treating conditions associated with loss of function of TREM2, such as neurodegenerative diseases; and pharmaceutical compositions comprising the compounds.

The invention relates to in vitro detection of biomarkers associated with drug-induced liver injury; belongs to the technical field of immunokits. The technical scheme provided by the invention is as follows: the soluble myeloid cell triggered receptor-1 is applied to preparation of a product for diagnosing the drug-induced liver injury as a biomarker. The invention discloses and proves that sTREM1 in serum or plasma can be used as a specific biomarker for diagnosing drug-induced liver injury (DILI), especially drug-induced liver fatty degeneration injury for the first time. The serum / plasma sTREM1 can detect abnormal rise in the extremely early stage (such as 7 days after medication) of the drug-induced liver injury, which is about 5-7 days earlier than that of the traditional marker ALT / AST, so that a key early intervention time window is provided for clinicians, and the liver injury can be prevented from further worsening.

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human PIL-RA and compositions comprising such antibodies or antigen-binding fragments thereof. In a particular aspect, the antibodies or anti-gen-binding fragments thereof that specifically bind to human PILRA block binding of PILRA to ligand and / or decrease cell surface PILRA. In further aspects, the antibodies or antigen-binding fragments can be used to treat diseases or conditions associated with myeloid cell dysfunction.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 ("TREM2"). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

The invention provides a brain glioma immune microenvironment complexity assessment method and application, and the method comprises the following steps: obtaining m glioma samples, and carrying out transcriptome determination on each cell in each glioma sample to obtain transcriptional expression profile data of the cells; carrying out clustering analysis on transcriptional expression profile data of the single cells through K-means clustering, and preliminarily identifying lymphocytes and myeloid cells according to immune cell classical markers; carrying out clustering analysis on the identified transcription expression profile data of the lymphocytes and myeloid cells, and identifying n cell subgroups; calculating the enrichment score of the characteristic gene set of each cell subset in the glioma transcriptome sample, wherein the higher the score is, the higher the enrichment proportion of the cell subset in the sample is; and evaluating the complexity of immune cell enrichment in the glioma sample based on the enrichment score of the characteristic gene set. The immune cell infiltration complexity can be predicted, and the relationship between immune cell enrichment complexity and brain glioma prognosis can be identified.

Provided are bispecific antibodies comprising first and second VIIII binding domains that specifically bind to the extracellular domains of interleukin- 10 receptor (IL-10R) alpha subunit (IL-10Rα) and beta subunit (IL-10Rβ), and that selectively suppress activation of myeloid cells and induce minimal or no direct activation of T cells or B cells.

The invention provides a drug combination composition for in-vivo target cell engineering modification, and target cells do not include myeloid cells. The drug combination composition comprises a first drug and a second drug, wherein the active ingredient of the first drug is a substance capable of saturating, inhibiting or eliminating phagocytic ability of in-vivo myeloid cells, and the active ingredient of the second drug is an in-vivo target cell capable of being engineered. Through combined application of the myeloid cell inhibition drug and the cell engineering modification drug targeting the target cells, endocytosis of the myeloid cells to the target drug is reduced or eliminated before engineering modification of the target cells, so that the off-target effect is reduced, the lymphatic organ targeting property can be improved, and the treatment effect of the myeloid cells is improved. The toxic and side effects of cell engineering modification drugs on the liver are reduced, and the method has important significance on in-vivo (in-situ) lymphocyte engineering modification (including gene editing) or immunotherapy (such as in-vivo CAR T cell therapy).

This invention relates to a liposomal formulation based on myeloid cell regulation and chemotherapy enhancement, along with its preparation method and antitumor applications, belonging to the technical field of pharmaceutical formulations. The liposomal formulation uses liposomes as carriers to co-load the CD11b agonist leukadherin-1 (LA1) prodrug (DSPE-PEG2000-Azo-LA1) and the gemcitabine prodrug Gem-SS-Chol. DSPE-PEG2000-Azo-LA1 contains a hypoxia-responsive azobenzene linker, and Gem-SS-Chol contains a glutathione-responsive disulfide bond, enabling precise drug release within the tumor microenvironment. This formulation exhibits uniform particle size and good stability, synergistically exerting chemotherapeutic and immunomodulatory effects. It effectively inhibits the proliferation and migration of pancreatic cancer tumor cells, enhances tumor cell immunogenic cell death, regulates the phenotype of myeloid immune cells in the tumor immunosuppressive microenvironment, and improves the therapeutic effect of pancreatic cancer. This invention provides a novel and highly efficient liposomal formulation for pancreatic cancer treatment, focusing on myeloid cell regulation and chemotherapy enhancement.

Provided herein are anti-TREM1 antibodies and related methods of making and using anti-TREM1 antibodies. Also provided are methods and compositions for enhancing an immune response in an individual and / or for treating an immune-related disorder, e.g., cancer, in an individual, including killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM1 antibody or antigen-binding fragment thereof.

To provide a method for producing professional antigen-presenting cells, and to provide the professional antigen-presenting cells.SOLUTION: Provided are a method for producing professional antigen-presenting cells, including obtaining proliferative myeloid cells (pMC) by expressing c-MYC or the like in myeloid cells (MC) differentiated from pluripotent stem cells, and obtaining professional antigen-presenting cells (pAPC) by expressing GM-CSF and / or M-CSF in the pMC, and human professional antigen-presenting cells produced by the method.SELECTED DRAWING: None

Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease and death in Europe. There are few pharmacological treatments for hepatic inflammation associated with alcohol abuses (ASH), the main driver of ALD progression. CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the context of ALD. The inventors therefore explored its contribution to ASH development in mice and its expression in ALD patients. Mice with a global (Cd44- / -) or myeloid cell specific (Cd44myel-KO) deficiency of CD44 were subjected to chronic plus one binge (CPB) ethanol feeding or chronic ethanol feeding. Human CD44 expression was assessed in liver biopsies obtained from patients with ALD. In this context, the present invention relates to a method of treatment of alcohol-related liver disease (ALD) in a subject in need thereof comprising administering to the patient a therapeutically effective amount of an inhibitor of CD44 standard (CD44s) or an inhibitor of its CD44 variant (CD44v) isoforms.

Provided are approaches to treating, inhibiting the progression of, or preventing disorders associated with the presence of immunosuppressive activity of myeloid-derived suppressor cells (MDSCs). The methods include administering an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) to an individual in need of prophylaxis or treatment of the disorder associated with the presence of the MDSCs. The NAMPT inhibitor can be combined with other agents or treatments to provide an enhanced effect.

The present disclosure provides, inter alia, therapeutic binding agents that can direct the activity of myeloid cells to a target population of cells, such as cancer cells.

The invention discloses a target-switchable CAR-T cell linker system and application thereof, belongs to the field of biological medicine, and particularly relates to a target-switchable linker system for improving activation and amplification of specific T cells. The linker comprises a domain capable of binding to an antigen-specific T cell (such as CAR-T), and a targeting domain capable of recognizing a cell surface membrane protein (such as FRbeta). By means of the linker, CAR-T cells can be switched to be in a targeted FRbeta functional state, so that the T cells can recognize and kill myeloid cells or macrophages expressing FRbeta, and activation, amplification and function enhancement of the antigen-specific T cells are achieved. According to the invention, the continuous activation capability and the anti-tumor effect of the CAR-T cells in a tumor microenvironment can be obviously improved, the exhaustion is reduced, and the treatment safety is enhanced.

The present invention provides attenuated immunostimulatory bacteria whose genome is modified to, for example, reduce toxicity and increase anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, increasing resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T cell function. The increase in phagocyte colonization improves delivery of encoded therapeutic products to the tumor microenvironment and into the tumor, and allows for routes of immunostimulatory bacteria administration such as systemic administration.

The invention relates to the technical field of biology, and particularly discloses application of macrophages in improving immunotherapy stomach cancer. The synergistic effect of CLEC2D + macrophages and a CD161 receptor in gastric cancer immune escape is focused for the first time, the single attention on macrophage M1 / M2 polarization and T cell checkpoint molecules in traditional research is broken through, a new T cell depletion mechanism driven by direct interaction of myeloid cells and lymphocytes is disclosed, and supplement is provided for the tumor immune escape theory; a novel blocking agent (such as a CD161 targeting antibody and a small molecule inhibitor) is developed on the basis of a mechanism of activating and mediating T cell depletion by a CD161 receptor, a basic mechanism research is directly converted into an innovative treatment scheme, and a differentiated strategy is provided for gastric cancer immunotherapy in combination with an existing PD-1 / PD-L1 inhibitor.

The invention discloses application of KAT7 as a pulmonary fibrosis diagnosis and prognosis biomarker and a treatment target. The research finds that the lysine acetyltransferase KAT7 is remarkably up-regulated in lung tissues of human pulmonary fibrosis patients and mouse fibrosis models, and is mainly expressed in macrophages; kat7 is specifically knocked out from myeloid cells, so that lung inflammation and fibrosis processes of mice can be remarkably relieved; further research finds that the fibrosis promoting function of macrophages can be down-regulated by inhibiting the activity of KAT7, and the generation and deposition of collagen can be reduced. Research results of the invention reveal the key driving effect of KAT7 in pulmonary fibrosis, a new marker is provided for diagnosis and prognosis of pulmonary fibrosis, and a new target is provided for prevention and treatment of pulmonary fibrosis.

The invention relates to the technical field of biological pharmacy, in particular to a tri-specific antibody and application thereof. According to the invention, an HER2 single-chain antibody, a CD89 single-chain antibody and an LAIR2 extracellular region are integrated into the same IgG1 Fc skeleton through a genetic engineering means to form a symmetric three-target binding molecule. The N end of the protein is scFv of HER2 and CD89, and tumor cells and myeloid cells can be bridged; and the C end is fused with LAIR2 through a flexible connecting peptide, so that collagen can be captured with high affinity, and an LAIR-1 inhibition signal is blocked. The trispecific antibody provided by the invention remodels an immunosuppressive tumor microenvironment by synergistically activating innate and adaptive immune pathways, and is suitable for treating HER2 positive solid tumors rich in collagen.

The invention relates to the field of biological medicine, and discloses application of ZBTB16 as a target spot in preparation of a medicine for treating clostridium difficile colitis. According to the application, it is found for the first time that the ZBTB16 protein is a key factor for regulating Pyrin inflammasome activation and clostridium difficile colitis pathogenesis, and it is proved that the ZBTB16 protein expressed by myeloid cells mediate ASC adaptive protein oligomerization under TcdB stimulation, so that complete lysis of caspase-1, IL-1beta maturation and pyroptosis induction are promoted, and the processes jointly promote the progress of serious intestinal inflammation. Furthermore, according to the application, the CC-3060 is found to successfully block pathological release of IL-1beta in macrophages and living body infection models caused by clostridium difficile toxins by inducing ZBTB16 protein degradation.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 (“TREM2”). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

The present invention provides novel viral vectors for use in human therapy, particularly for use in the treatment of diseases or disorders that originate in or are based in the brain, particularly PGRN-associated neurodegenerative diseases or disorders, including frontotemporal degenerative diseases or disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. The present invention also provides viral vectors for use in the treatment of brain tumors, particularly brain tumors selected from the group consisting of glioblastoma, glioma, ganglioneuroblastoma, astrocytoma, oligodendroglioma, PNET (primitive neuroectodermal), medulloblastoma, CNS lymphoma, and neuroblastoma, or any other CNS tumor, and further for use in the treatment of brain metastases originating from any form of breast cancer, lung cancer, colon cancer, testicular cancer, renal cancer, and melanoma or any other solid tumor, as well as any hematological tumor, including all forms of leukemia and lymphoma.

Provided herein are antibodies that bind signal regulatory protein gamma (SIRPy), as well as SIRPα and / or SIRPβ1, and methods of using such antibodies (referred to as SIRP antibodies). In some embodiments, the SIRP antibodies are human monoclonal antibodies that bind human SIRPy as well as SIRPα and / or SIRPβ1. In some embodiments, the SIRP antibodies provided herein are useful for treating a disease or condition associated with overactivation and / or hyperproliferation of lymphocytes, myeloid cells, or a combination thereof, or a disease or condition associated with SIRPα, SIRPβ1 and / or SIRPy activity.