61 results about "FOXP3" patented technology

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

A kit for detecting expression of AIRE and Treg in lymphatic tissue infected by EB virus comprises colloidal quantum well antibody conjugates, including a colloidal quantum well and protein AIRE and GITR conjugates and a colloidal quantum well and antibody CD25 and Foxp3 conjugates. The detection method comprises the following steps: (1) carrying out slicing treatment on a lymphatic tissue, and carrying out antigen repair by using an antigen repair liquid; (2) respectively adding colloidal quantum well proteins or antibodies coupled with different targets to dye the sections; (3) carrying out nucleus staining; and (4) collecting multi-channel fluorescence image information of the tissue slice, and judging expression levels and mutual relations of AIRE, Treg cells and dendritic cells in immune tolerance in combination with spatial positioning and intensity distribution of fluorescence signals of different channels. According to the invention, qualitative or quantitative multi-parameter and high-precision detection of the immune tolerance related cells in the lymph tissue is realized.

The present invention relates to methods for carefully monitoring and evaluating the efficacy of cell therapy in patients treated with CD4+FoxP3+ regulatory T cells. Further subject matter relates to cell therapy methods using CD4+FoxP3+ regulatory T cells and the monitoring methods of the invention.

Disclosed are methods of making a genetically cell that expressed FOXP3 and methods of treatment. In some embodiments, the method can providing a first nucleotide sequence, wherein the first nucleotide sequence comprises a coding strand, the coding strand comprising one or more regulatory elements and a FOXP3 gene or portion thereof providing a nuclease and performing a gene editing process on the first nucleotide sequence, which edits said one or more regulatory elements, and optionally edits the FOXP3 gene or portion thereof. Methods of treating a subject suffering from an autoimmune disease and subjects suffering the effects of organ transplantation are also provided.

The invention belongs to the technical field of biological medicine, and particularly relates to a new Spp1 + Carmil1 + and Spp1 + Cav1 + macrophage subgroup, a screening method and application in diagnosis and treatment of rheumatoid arthritis (RA). Aiming at the function limitation of a traditional M1 / M2 classification model, the invention proves the following new subgroup pathological interaction mechanism: osteoclast (ACP5 +) specifically releases TNFSF11 (RANKL), and is co-localized with Spp1 + Carmil1 + and Spp1 + Cav1 + subgroup space; the Spp1 + Carmil1 + subgroup secretes IL-18, and space interaction exists between the Spp1 + Carmil1 + subgroup and Treg (Foxp3 +) and Th17 (Il17a +) cells. The invention provides a novel cell marker and a targeted treatment strategy for accurate diagnosis and treatment of RA.

A method for determining whether a subject is at risk for having a progressing or high-grade pre-invasive lesion, nodule or small mass, or having a solid malignant tumour is described the method comprising: (i) determining a ratio of activated and / or exhausted T cells:naive and / or resting T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence or absence of a panel of biomarkers comprising Ki67 and CD39, or (ii) determining a ratio of activated and / or exhausted T cells:T cells which are not activated and / or exhausted T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence or absence of a panel of biomarkers comprising Ki67 and CD39, (iii) determining a proportion of activated and / or exhausted T cells as a percentage of T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence of a panel of biomarkers comprising Ki67 and CD39, and / or (iv) determining a proportion of activated and / or exhausted T cells as a percentage of T cells in a sample of blood obtained from the subject, wherein the T cells are CD4 T cells, and wherein the determining comprises analysing T cells using cytometry to detect the presence of a panel of biomarkers comprising FoxP3.

The present application relates to the medical technical field, especially to the application of FYB1 gene as a marker in preparation of gastric cancer diagnosis or prognosis judging reagent. The present application research finds that FYB1 gene is highly expressed in gastric cancer tissue and negatively correlated with the prognosis of patients, and can be used as a gastric cancer marker for gastric cancer detection and efficacy evaluation. In addition, FYB1 is positively correlated with the expression of Treg cell marker FOXP3 and co-localized in tissues, suggesting that FYB1 may promote gastric cancer tumor immune escape; the expression of FYB1 gene can significantly inhibit the proliferation, migration and invasion ability of gastric cancer cells, and inhibit tumor growth, indicating that FYB1 gene can be used as a gastric cancer treatment target and play an important role in the treatment of gastric cancer patients.

Some aspects relate to engineered cells comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) and at least at first coding exon of a FOXP3 gene, where expression of the CAR and FOXP3 are linked, such that CAR+ cells have a regulatory T cell (Treg) phenotype. Some aspects relate to methods of producing engineered cells in which expression of a CAR and FOXP3 are linked, thereby reducing the incidence of contaminating CAR+ T effector cells. Further aspects relate to methods of screening CARs suitable for expression by a Treg. Some aspects relate to engineered cells expressing an anti-CD19 chimeric antigen receptor (CAR). Some aspects relate to methods of producing engineered cells expressing an anti-CD19 CAR. Some aspects relate to uses of cells expressing anti- CD19 CARs.

The invention provides methods of isolating CD 127lo / − immunosuppressive regulatory T cells which can be greatly enriched for FoxP3, methods of expanding the isolated cells, pharmaceutical compositions of such cells, and methods of their use in the treatment of autoimmune and other immune system mediated disorders.

Compositions comprising at least one nanoparticle containing a nucleoside RNA molecule encoding FOXP3 and an optional second agent are described herein. In some cases, the RNA molecule is circular and contains one or more IRES. Methods for treating or preventing inflammation are also described herein.

This application discloses an IL-2 variant fusion protein and its applications. The IL-2 variant fusion protein of this application comprises 1) wild-type hIL-2 or an hIL-2 mutant protein, 2) an hIgG1-HC-Fc mutant fragment, and 3) an hIgG1-LC fragment; the hIL-2 mutant protein is obtained by an N88D mutation in wild-type hIL-2; the hIgG1-HC-Fc mutant fragment is obtained by L236A, L237A, and P331G mutations in wild-type hIgG1-HC-Fc. This IL-2 variant fusion protein, as a novel drug, can regulate Tregs (Foxp3). + ), treatment for Tregs (Foxp3) + This is associated with various refractory autoimmune diseases and inflammation, and prolongs the duration of Tregs (Foxp3). + Related health and lifespan span.

Compositions and methods are described herein that are useful for the detection of prostate cancer progression by determining the expression levels of genes associated with metastatic PCa. Based on the expression of IL-6, SELE, FOSB, NRK, NFRB2, FOXP3, ARG1, CEBPDP, TNFα, ADAMTS4, PENK, FOSL1, DUSP1, ACTA1, AGT, ATF3, CDK1, CXCL8, SELP, VCAN, TFP12, or NR4A3 genes or any combination thereof, treatment of PCa with SELE agonists, TNFα antagonists, and / or immune checkpoint inhibitors (ICIs) are shown to be effective.

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

Interleukin-34 is a cytokine that is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Recent work has also demonstrated a new and possible therapeutic role for IL-34 as a Foxp3+ Treg-secreted cytokine mediator of transplant tolerance. New mutated IL-34 polypeptides have been generated, which can be used as agonists or antagonists.

The invention belongs to the technical field of biological medicine, provides a mustard gas immunotoxicity evaluation method based on Foxp3 promoter methylation, and evaluates the application effect of the Foxp3 promoter methylation level in mustard gas immunotoxicity evaluation in combination with in-vitro cell experiments and in-vivo animal experiments. Results show that Treg cell deficiency is a main reason for tissue damage and inflammation caused by mustard gas poisoning, cell fate and functions of the Treg cell deficiency are mainly regulated and controlled by Foxp3 transcription factors, mustard gas can cause increase of the DNA methylation level of Foxp3 gene loci, DNA hypermethylation of Foxp3 promoters is crucial to Treg cell differentiation inhibition, Th17 / Treg imbalance and systemic inflammation caused by mustard gas exposure, and the Treg cell deficiency is a main reason for tissue damage and inflammation caused by mustard gas poisoning. The methylation level of the Foxp3 promoter can be used as a marker of a mustard gas immunotoxicity evaluation method.

The present invention provides an activator of CD4+Foxp3+ regulatory T cells for use in treating or preventing an inflammatory epidermal disease in a subject, wherein the disease is characterised by a

The invention relates to the technical field of cellular immunotherapy, and discloses an application of a CD74 positive regulatory T cell in treatment of graft versus host disease, the CD74 positive regulatory T cell is composed of the following components in proportion: in a sorted and purified cell population, the proportion of regulatory T cells with CD4 + CD25 + CD127-phenotype is 85-95%, the proportion of regulatory T cells with CD25 + CD127-phenotype is 1-5%, and the proportion of regulatory T cells with CD24 + CD25 + CD127-phenotype is 1-5%. Wherein the CD74 high-expression subgroup accounts for 60-75% of the total amount of the regulatory T cell, the cell subgroup functional immune molecule combination comprises CTLA4, FOXP3, TIGIT and TNFRSF18, when the CD74 positive regulatory T cell is used for treating graft versus host disease, the CD74 positive regulatory T cell is firstly used for preventive infusion, single infusion is performed on the day of transplantation, the dosage is 5 * 10 < 5 > cells / receptor, and then the CD74 positive regulatory T cell is used for treating the graft versus host disease. The CD74 positive regulatory T cells are used for repeated therapeutic infusion when early aGVHD symptoms occur, graded treatment is carried out, pathological immune response is inhibited to the maximum extent, immune tolerance is promoted, the treatment is carried out once a week and 2-3 times in total, and the dosage of each time is 1 * 10 < 6 > cells / receptor.

The present invention relates to a lipid nanoparticle comprising an mRNA encoding FOXP3 and at least one second polypeptide wherein the lipid nanoparticle comprises a moiety capable of specifically binding to a molecule expressed on CD4 + T cells, and wherein the mRNA is modified to an increased stability compared to an unmodified mRNA.

The present invention provides methods, systems, and kits for determining responsiveness of a subject with or susceptible to cancer to anti-PD1 immune checkpoint inhibitor immunotherapy (ICII) including determining the level of one or more of markers CD15 in CD8+Ki67 / CD71+ or CD8 / CD4−Ki67 / CD71+ T cells, CTLA-4 in CD4+Ki67 / CD71+ T cells, FoxP3 in CD4+Ki67 / CD71+ T cells, Ki67 or CD71 in CD8+ T cells, wherein an increase in CD15, CTLA-4, FoxP3, or a decrease in Ki67 or CD71 prior to immunotherapy is indicative that the subject is responsive to immunotherapy, particularly PD1 ICII.

The invention discloses application of timosaponin AIII in preparation of a curative effect enhancer for CAR-T cell therapy and a product for overcoming drug resistance. The invention proves that TAIII is an allosteric inhibitor of an adenosine A2A receptor, and blocks a downstream signal channel through allosteric combination with A2AR, so that expression of a transcription factor FoxP3 is inhibited, Tregs in a CAR-T product is selectively cleared, immunosuppression of the Tregs on effector T cells is relieved, meanwhile, the proportion of central memory T cells is increased, and amplification, durability and cytokine secretion functions of the CAR-T cells are enhanced. The invention further provides a CAR-T cell composition containing the TAIII, and the TAIII and the CAR-T cells are combined or used as a pretreatment agent, so that the tumor removal capability can be remarkably enhanced, and recurrence after treatment can be effectively prevented. The invention provides a safe and effective new strategy for enhancing the anti-tumor activity of the CAR-T cells and overcoming the drug resistance of the CAR-T therapy.

The invention discloses a preparation method and application of a mesenchymal stem cell exosome which is enriched with Foxp1 protein and has immune organ targeting property. The method comprises the following steps: acquiring a single-cell suspension of the mesenchymal stem cells, performing suspension culture on the single-cell suspension of the mesenchymal stem cells in an exosome removal culture medium to induce the mesenchymal stem cells to aggregate to form a compact cell cluster, and then collecting the exosome through differential centrifugation. According to the method disclosed by the invention, the mesenchymal stem cells are induced to aggregate through a suspension culture technology, so that the exosome with high yield and immune targeting is obtained. The Foxp1 protein is specifically enriched in the exosome, the exosome has the characteristics of high yield, immune organ targeting and strong immune regulation capability, Treg cell differentiation is regulated through the Foxp1 / STAT5 / Foxp3 axis, the limitation in the application of the existing exosome is solved, and a new strategy is provided for the treatment of autoimmune diseases.

Methods, polynucleotides, and compositions for generating engineered Treg cells are provided. The methods, polynucleotides, and compositions enable the reprogramming of hematopoietic cells into Treg cells by constitutive or controlled expression of FOXP3 in engineered cells, so that engineered Treg cells can suppress the activation and proliferation of responder T cells.

The present disclosure provides an induced regulatory T cell having high functionality and a stable immunosuppressive function. The present disclosure provides an induced regulatory human T cell having at least one characteristic selected from the group consisting of FoxP3 positive, CTLA4 positive, NT5E positive, ITGAE (CD103) positive, AREG positive, CD172g positive, and CD26 positive, and a cell population comprising the same. The present disclosure also provides compositions comprising such cells, pharmaceutical compositions, methods of using the same, and the like.

The invention relates to the field of immunology and cell therapy, in particular to application of rTh1 cells in preparation of drugs for preventing or treating allergic diseases or inflammatory diseases, the phenotypes of the rTh1 cells are CD3 (+), CD4 (+), CD25 (-), Foxp3 (-), CXCR5 (-), CCR6 (-), CXCR3 (+), CD73 (+) and cMaf (+), and FR4, PD1 and ICOS are highly expressed. The novel T cell subset rTh1 cell has an immunoregulation function, and has an important value in prevention and treatment of allergic diseases such as food allergy and dust mite allergy, atopic dermatitis, allergic asthma, chronic obstructive pulmonary disease and other Th2-type inflammation related skin diseases such as pemphigus bullosa and urticaria.

The absence of regulatory T cells (Treg) may underlie disorders including but not limited to autoimmunity, dermatitis, periodontitis and even transplant rejection. Enhancing local numbers of Treg through in situ Treg expansion or induction is contemplated herein as a treatment option for these disorders. Current methods for in vivo Treg expansion are not Treg specific and are associated with many adverse side-effects. The data presented herein provides in vitro testing of a Treg-inducing microparticle providing a predictable controlled release for combinations of cytokines and drugs (e.g., IL-2, TGF-β, and / or rapamycin) resulting in targeted Treg migration. These controlled release microparticles are also capable of inducing FoxP3+ Treg in human cells in vitro suggesting that these compositions be developed into an in vivo Treg induction and expansion therapy.

The described technology pertains to biotechnology, specifically methods and systems for modulating FOXP3 expression in human CD4+ T cells using CRISPR-based genomic editing techniques. FOXP3, a transcription factor essential for regulatory T cell (Treg) function, is constitutively expressed in Tregs but transiently expressed in conventional CD4+ T cells (Tconvs) upon activation. The approach addresses challenges in precise modulation of FOXP3 expression by identifying cis-regulatory elements, such as CNSO, NCNS, and PPP, and trans-regulatory factors, including GATA3, STAT5, and ETS1, that influence FOXP3 expression in Tconvs. Utilizing CRISPR interference (CRISPRi) and CRISPR nuclease (CRISPRn) screens, the methods enable targeted, cell-type-specific modulation of FOXP3 levels. Applications include engineered T cell therapies for autoimmune diseases, cancer, and transplantation. Advanced epigenetic editing tools, such as CRISPRoff, further enhance specificity by targeting DNA methylation states at regulatory loci. This approach offers scalable solutions for programming FOXP3 expression in diverse therapeutic contexts.

The present invention relates to universal immunomodulatory T cells comprising a chimeric antigen receptor and uses thereof and, specifically, to universal immunomodulatory T cells in which immunogenicity of cells is removed so that general T cells obtainable in sufficient numbers from healthy people can be applied to all organ transplant patients and in which Foxp3 and a chimeric antigen receptor are both introduced, and a use thereof.

An expression construct, a nucleic acid or vector or cell comprising said expression construct, and various uses of said expression construct, nucleic acid, vector or cell is disclosed herein. Particularly, an expression construct comprising a PGK promoter operably linked to (i) a first nucleotide sequence encoding a chimeric antigen receptor (CAR), and (ii) a second nucleotide sequence encoding a FOXP3 polypeptide, wherein the first nucleotide sequence is located upstream of the second nucleotide sequence, is provided.

The invention relates to a method for separating and amplifying human regulatory T cells in vitro, which comprises the following steps: recovering and incubating healthy human PBMC (peripheral blood mononuclear cells), sequentially separating CD3 + T cells and CD25 + T cells through a Metensi Pan T kit, separating the CD25 + T cells through Thermo CD25 magnetic beads, activating the cells through a Palesei CD3 / CD28 magnetic bead, and finally carrying out multiplication culture in a culture medium containing 1000 IU / ml of IL-2, 10 ng / ml of TGF-beta and 100 nM of rapamycin. The expression of CD3, CD25 and Foxp3 is detected through flow cytometry on the third day of culture, and the purity of Treg is evaluated by using a Biolegend CD3 / CD25 antibody and a Thermo FOXP3 antibody. The method breaks through the bottleneck of a traditional process, the Treg purity is larger than 70%, amplified cells show the capacity of strongly inhibiting T cell proliferation in in-vitro co-culture, and a reliable scheme is provided for large-scale preparation of high-stability Treg cell products.

The application provides a kind of marker for predicting the curative effect of lung cancer immunotherapy and the construction method of scoring system, and relates to the field of biotechnology.The inventors have found that the mRNA of CypB, the RNA transcribed by FAM83H-AS1 gene and LncRNA VPS9D1-AS1 are related to the prognosis of lung cancer, and the immune cell infiltration around lung cancer lesions is related to the treatment of lung cancer patients.Accordingly, the application takes the mRNA of CypB, the RNA transcribed by FAM83H-AS1 gene, LncRNA VPS9D1-AS1, panCK, CD3, CD4, CD8 and Foxp3 as markers, and provides a construction method of scoring system for predicting the curative effect of lung cancer immunotherapy.The scoring system constructed by the method can comprehensively evaluate the state of tumor and its microenvironment, accurately predict the progression risk and prognosis of lung cancer, and better guide clinical medication.