86 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.

The present invention relates to a method of preserving CD62L expression in an isolated regulatory T cell (Treg) population that has been cryopreserved, comprising introducing a polynucleotide encodin

The invention relates to the technical field of primary local hyperhidrosis, in particular to a biomarker for detecting primary local hyperhidrosis and application of the biomarker, and the biomarker comprises but is not limited to one or more of the ratio of Th17 cells to Treg cells, IL-17A, IL-6, ROR gamma t and FoxP3. According to the invention, a multi-dimensional detection system covering PFH core pathological links (immune disorder, hyperactivity of sympathetic nerves and hyperfunction of sweat gland) is constructed by integrating immune related markers such as Th17 / Treg cell ratio, IL-17A, IL-6, ROR [gamma] t, FoxP3 and the like and combining the concentrations of peripheral blood epinephrine (E) and noradrenaline (NE) and the gene expression levels of sweat gland tissues AQP5 and Cacna1c. And a potential molecular target is provided for developing a novel therapeutic strategy (such as specific blocking of an IL-17 signal channel or enhancement of a Treg function) of a targeted Th17 / Treg axis.

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 present application relates to interleukin-2 variants and methods of use thereof. The present invention relates to polypeptides that share a primary sequence with human IL-2 in addition to several mutated amino acids. A panel of IL-2 variants comprises mutations with profound impressive manufacturability that preferentially promote proliferation, survival, activation and / or function of immunosuppressive regulatory T cells (Treg: CD4 + CD25 + FoxP3 +) over effector T cells and NK cells. Also included is the therapeutic use of such IL-2 selective agents, alone or in combination with immunomodulators or disease tissue targeting antibodies, proteins or peptides, for the treatment of Treg cell deficiency, various autoimmune and inflammatory disorders, organ transplantation and graft versus host disease. In another aspect, the invention relates to pharmaceutical compositions comprising the disclosed polypeptides. Finally, the invention relates to the therapeutic use of the disclosed polypeptides and pharmaceutical compositions due to their selective modulation of the immune system on diseases such as autoimmune and inflammatory disorders.

The invention discloses a fusion protein, cell membrane particles containing the fusion protein and application of the fusion protein. The fusion protein comprises a CD8 antibody and an IL-2 mutant, the CD8 antibody and the IL-2 mutant are connected through a cleavable connecting assembly, and the IL-2 mutant can stimulate Treg proliferation in a biased mode. The prepared cell membrane particle for expressing the aCD8-IL2 fusion protein can enhance retention and proliferation of Foxp3 + T cells in spleen and pancreas islet in a mouse body and reduce infiltration of CD8 + T cells, so that the cell membrane particle can be applied to immunotherapy of new type I diabetes mellitus.

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.

Cell therapy compositions comprising engineered human regulatory T cells (eTregs) characterized by ectopic overexpression of FOXP3 and Helios protein, produced via introduction of separate nucleic acid constructs respectively encoding FOXP3 and Helios (FOXP3+Helios+ eTregs). Cell therapy compositions comprising mixed populations of CD4+ and CD8+ Treg cells each with ectopic overexpression of FOXP3 and Helios. Methods of making and use the same for therapies involving inflammation and / or a disorder of the immune system.

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 invention discloses a method for separating and purifying aTreg cells in a mouse body, and relates to the field of cell sorting, the method comprises the following steps: dyed mouse lymphocytes are sorted through flow cytometry, and markers of dyeing action comprise one or more of CD4, Foxp3, CD44 and CD62L. According to the present invention, the multiple markers are dyed, and then the flow cytometry is adopted to perform sorting, such that the operation is simplified, the survival aTreg cells are separated and extracted under the combined action of the multiple dyed markers so as to improve the sorting purity of the extracted aTreg cells.

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 relates to a molecular marker for immunotherapy prediction of a targeting shower cell and application of the molecular marker, and belongs to the technical field of molecular biology. The invention provides a molecular marker for immunotherapy prediction of a targeting shower cell. The molecular marker comprises CD8, CD4, PD-1, Foxp3, CD19 and CD3, wherein the CD8, the CD4, the PD-1, the Foxp3, the CD19 and the CD3 are used for immunotherapy prediction; or comprises a CD45, a CD45RA, a CD45RO, a CD25, a CCR7 and a CD127; or comprises CD3, LAG3, Tim3, ICOS, CD69 and CD103; or comprises a CD79A, a CD79B, a CD20, a CD21 and a CD138; or the CD56, the CD161, the CD57, the CD94 and the Granzyme B are included; the invention relates to a CD56, CD161, CD57, CD94 and Granzyme B. The CD56, the CD161, the CD57, the CD94 and the Granzyme B. The molecular marker can accurately distinguish shower cell groups and interaction.

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 relates to regulatory T cell and uses thereof. By their immunosuppressive and anti-inflammatory activities, regulatory T cells play a central role in peripheral tolerance and thus critically prevent the development of autoimmune and inflammatory disorders. The inventors showed that Foxp3+CD4+ Tregs express high levels of LTα, which negatively regulates their immunosuppressive signature. They demonstrated that the adoptive transfer of LTα− / − Tregs in mice protects from dextran sodium sulfate (DSS)-induced colitis and attenuates inflammatory bowel disease (IBD), multi-organ autoimmunity and the development of CAC. The inventors also showed that by mixed bone marrow chimeras that LTα expression specifically in hematopoietic cells negatively controls the immunosuppressive signature of Tregs. In particular, the present invention relates to regulatory T cell characterized in that it does not express or expresses reduced levels of lymphotoxin alpha.

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 invention relates to the field of tumor diagnosis and prognosis evaluation, in particular to a lung cancer prognosis prediction method based on an FOXP3 expression level, which comprises the following steps: collecting a tissue sample of a lung cancer patient, fixing, dehydrating, transparentizing, embedding, preparing a slice, performing FOXP3 immunohistochemical staining, and evaluating the FOXP3 expression level. In combination with clinical data of a patient, analyzing the influence of FOXP3 expression and clinical features on prognosis by applying a Cox proportional risk regression model, and constructing a prognosis evaluation model; determining an optimal prognosis tangent point value of FOXP3 expression through an ROC curve, and dividing patients into a high expression group and a low expression group; finally, according to the prognosis evaluation model and FOXP3 expression grouping, the prognosis risk and survival probability of the patient are predicted, an important basis is provided for clinical treatment and prognosis judgment, a standardized FOXP3 immunohistochemical detection method is provided, and the accuracy and repeatability of results are ensured.

The invention provides a lentiviral vector comprising a construct comprising from 5' to 3': (a) a first nucleotide sequence encoding FoxP3; (b) a second nucleotide sequence encoding a cleavable linker; and (c) a third nucleotide sequence encoding a CD19 CAR.

The present invention relates to a method of preserving CD62L expression in a regulatory T cell (Treg) population that has been cryopreserved, comprising introducing a polynucleotide encoding a FOXP3

Described herein are compositions and methods for engineering Treg cells for treatment of diabetes. The engineered Treg cells provided herein may be dual-edited (i.e., edited in two different loci in the cell genome), a first locus being the FOXP3 locus and the second locus being the TRAC locus. The engineering of dual-edited Treg cells as provided here may include selective expansion of dual-edited cells using a ligand that initiates and / or maintains IL-2 signal transduction in dual-edited cells. The engineering of dual-edited Treg cells as provided here may stably express FoxP3 and an exogenous TCR.