160 results about "Myeloid cells" patented technology

Provided herein are anti-TREM2 antibodies and related methods of making and using anti-TREM2 antibodies. Also provided are methods and compositions for enhancing an immune response and / or for the treatment of an immune-related condition in an individual, e.g., cancer, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM2 antibody or antigen binding fragment thereof.

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 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.

The invention discloses a spleen-targeted nano platform construction method suitable for tumor vaccination, and particularly relates to the field of vaccines.The spleen-targeted nano platform construction method comprises the steps that S1, CL15H6-DOPS LNPs, spherical polymer vesicles and erythrocyte membrane coated nano-particles are selected as spleen-targeted nano-carriers; s2, integrating an immunologic adjuvant; mn < 2 + > doped LNPs, ultrasonic response lipidosome and a CD3 antibody are selected to be coupled to serve as an integration material; s3, delivering in vivo; animal models are selected for in-vivo delivery and curative effect verification, and B16F10 melanoma mice, MC38 colon cancer mice and non-human primates are selected as the animal models respectively. By optimizing the chain length and the surface topological structure (such as spherical polymer vesicles) of the liposome, the spleen enrichment rate is remarkably increased, and the red marrow myeloid cell uptake efficiency is enhanced. By combining with common delivery of a manganese adjuvant, an STING channel is activated, secretion of type I interferon is promoted, and the proportion of antigen-specific CD8 + T cells and the tumor inhibition rate are increased.

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 single domain antibodies (sdAbs) against TREM (triggering receptors expressed on myeloid cells) like transcript-1 (TLT-1) molecules that are present on activated platelets at the site of an injury, and especially on a subset of activated platelets, coated platelets. Furthermore, the present invention relates to fusion proteins comprising sdAbs against TLT-1 and an extracellular (soluble) domain of tissue factor (sTF), to direct targeting of such fusion proteins to activated platelets at the site of injury through binding of the sdAbs to TLT-1, a membrane protein receptor that is only present on activated platelets. Specific interaction of sdAbs with the TLT-1 receptor positions the sTF domain of the fusion to interact with, and activate, FVII. As a result, a targeted procoagulant effect is achieved at the site of injury via activated platelets. The fusion proteins are useful to treat individuals that have a bleeding disorder, such as hemophilia A, hemophilia B, or acute bleeding due to traumatic injury.

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 present invention relates to a human CD20 protein of which one or more intracellular domains are modified sufficient to reduce or eliminate intracellular signaling when attached to or bound to a cell membrane, such as T cells, natural killer cells, B cells, myeloid cells, pluripotent stem cells, and hematopoietic stem cells. The invention also relates to a nucleic acid encoding the modified human CD20 protein described herein, and the use of the modified human CD20 protein as a safety switch in chimeric antigen receptor T cell therapy or as a selection marker in gene therapy.

The present disclosure generally relates to the treatment of subjects having myeloid cell dysfunction or at risk of developing myeloid cell dysfunction by administering a Membrane Spanning 4-Domains A6A (MS4A6A) inhibitor and / or a Membrane Spanning 4-Domains A64A (MS4A4A) inhibitor to the subject.

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

The invention relates to a modified myeloid cell comprising a cytokine chimeric receptor (CCR), wherein said CCR comprises an extracellular domain comprising an extracellular domain of a cytokine receptor which binds soluble molecules present in the tumor microenvironment (TME); a transmembrane domain; and an intracellular signaling domain comprising CD40 cytotail, CD3zeta intracellular domain and / or STING or one of its fragments. The invention also relates to a modified cell comprising a CCR and a transgene coding for a cytokine. The invention also relates to therapeutic uses thereof and to methods and pharmaceutical compositions for the treatment of cancer.

The present invention provides a method of treating a disease or disorder caused by and / or associated with ABCD1 dysfunction in a human patient, the method comprising administering to the patient in need thereof an effective amount of a compound that increases the activity of triggering receptor expressed on myeloid cells 2 (TREM2). In some embodiments, compound that increases the activity of TREM2 is an agonist of TREM2. In some embodiments, the agonist of TREM2 is a small molecule agonist of TREM2 or an antibody agonist of TREM2.

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 present invention relates to a combination of a) myeloid cells and b) T cells, wherein the myeloid cells and the T cells are isogenic human cells, and wherein the myeloid cells and the T cells are derived from a T- cell-derived iPSC. The present invention also relates to the use of a combination of a) myeloid cells and b) T cells, wherein the myeloid cells and the T cells are isogenic human cells, and wherein the myeloid cells and the T cells are derived from a T-cell-derived iPSC in cell therapy. The present invention also relates to the use of a combination of a) myeloid cells and b) T cells, wherein the myeloid cells and the T cells are isogenic human cells, and wherein the myeloid cells and the T cells are derived from a T-cell-derived iPSC for drug screening.