84 results about "FOXP3 protein" patented technology

Numerous disease states, such as human allergic, autoimmune, and autoimmune diseases, and cancer, may be treated by targeting OX40 / OX4OL. OX4OL inhibits the generation of Tr1 cells from naïve and memory CD4+ T cells. This unique function of OX4OL is not shared by two other costimulatory TNF-family members, GITR-ligand and 4-1BB-ligand. It has been shown that signaling the OX40-receptor on human T cells by antibodies, small molecules, or the OX4OL modulates the generation and function of IL-10 producing Foxp3+ Treg immunosuppressive T cells and blocks Foxp3+ Treg function. Further, provided are high throughput methods for identifying compounds that can inhibit the immunosuppressive function of IL-10 producing Tr1 cells.

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining LNs, where it can potently activate Foxp3 regulatory T cells (Tregs). We now show that IDO functions as a molecular switch in tumor-draining LNs, maintaining Tregs in their normal suppressive phenotype when IDO was active, but allowing inflammation-induced conversion of Tregs to a polyfunctional T-helper phenotype similar to proinflammatory TH17 cells when IDO was blocked. In vitro, conversion of Tregs to the TH17-like phenotype was driven by antigen-activated effector T cells, and required IL-6 produced by activated pDCs. IDO regulated this conversion by dominantly suppressing production of IL-6 in pDCs, in a GCN2-kinase dependent fashion. In vivo, using a model of established B16 melanoma, the combination of an IDO-inhibitor drug plus anti-tumor vaccine caused upregulation of IL-6 in pDCs and in situ conversion of a majority of Tregs to the TH17 phenotype, with marked enhancement of CD8+ T cell activation and anti-tumor efficacy. Thus, Tregs in tumor-draining LNs can be actively re-programmed in vitro and in vivo into T-helper cells, without the need for physical depletion, and IDO serves as a key regulator of this critical conversion.

Provided herein are methods of treating a cancer in a subject comprising administering a FOXP3 protein, a nucleic acid encoding a FOXP3 protein, or an inducing compound which induces FOXP3 protein expression. Methods of altering a phenotype of a cancer cell or tumor cell, methods of inhibiting growth of such cells, and methods of inducing apoptosis of these cells are also provided herein. These methods comprise contacting the cell with a FOXP3 protein, a nucleic acid encoding a FOXP3 protein, or an inducing compound which induces FOXP3 protein expression. Further provided herein are diagnostic methods, comprising comparing the expression or structure of a FOXP3 protein or FOXP3 gene in a test sample to that of a normal or prior sample. A method of screening a test compound for anti-cancer activity comprising administering to cells the test compound and measuring FOXP3 protein or FOXP3 gene expression is moreover provided herein.

The invention discloses a sorting and amplification method of human peripheral blood CD4+CD25+Foxp3+ regulatory T cells, and belongs to the field of cell sorting amplification. The sorting and amplification method of the human peripheral blood CD4+CD25+Foxp3+ regulatory T cells specifically comprises the following steps: (1) separating peripheral blood mononuclear cells; (2) performing MACS (magnetic activated cell sorting) on CD4+CD25+Foxp3+Treg cells; and (3) performing in-vitro culture and amplification on the CD4+CD25+Foxp3+Treg cells, and finally performing amplification and culture to obtain the human peripheral blood CD4+CD25+Foxp3+ regulatory T cells. According to the sorting and amplification method disclosed by the invention, human peripheral blood CD4+CD25+Treg cells are successfully separated by using an immuno-magnetic bead two-step process, and the purity of the human peripheral blood CD4+CD25+Treg cells is subjected to flow identification to ensure that the purity of the finally-obtained CD4+CD25+Treg cells can reach 97%, and the activity of the cells can reach more than 95%.

The present invention relates to a method, in particular an in vitro method for identifying FoxP3-positive regulatory T cells, preferably CD25+CD4+ regulatory T cells of a mammal, comprising analysing the methylation status of at least one CpG position in the gene foxp3 or an orthologous or paralogous gene thereof, and the use of DNA-methylation analysis of the gene of the transcription factor FoxP3 for a detection and quality assurance and control of regulatory T cells. Furthermore, the present invention relates to a kit for performing the above methods as well as respective uses.

The invention provides methods for treating autoimmunity, for reestablishing tolerance, and for generally dampening or suppressing the activation state of the immune system. The methods involve the induction or activation of a particular regulatory T cell population, characterized by its expression of CD8, CD25 and Foxp3.

The present invention is directed to generating regulatory T cells by treating a cell culture that includes non-regulatory T cells with a regulatory composition. The invention encompasses methods utilizing a regulatory composition that includes agents that prevent methylation of the locus for the FOXP3 transcription factor, agents that accelerate differentiation of T cells into suppressor cells, and agents that are histone deacetylase inhibitors. The invention also encompasses compositions of regulatory T cells generated by culturing non-regulatory T cells with a regulatory composition as well as the use of such regulatory T cells in the treatment of autoimmune diseases and aberrant immune responses.

Numerous disease states, such as human allergic, autoimmune, and autoimmune diseases, and cancer, may be treated by targeting OX40 / OX40L. OX40L inhibits the generation of Tr1 cells from naïve and memory CD4+ T cells. This unique function of OX40L is not shared by two other costimulatory TNF-family members, GITR-ligand and 4-1BB-ligand. It has been shown that signaling the OX40-receptor on human T cells by antibodies, small molecules, or the OX40L modulates the generation and function of IL-10 producing Foxp3+ Treg immunosuppressive T cells and blocks Foxp3+ Treg function. Further, provided are high throughput methods for identifying compounds that can inhibit the immunosuppressive function of IL-10 producing Tr1 cells.

The present invention relates to the treatment, diagnosis, and prophylaxis of cancer based on the expression of foxp3.

The present invention relates to a method, in particular an in vitro method, for pan-cancer diagnostics, comprising identifying the amount and / or proportion of stable regulatory T cells in a patient suspected of having cancer through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein an increased amount and / or proportion of stable regulatory T cells in said patient is indicative for an unspecific cancerous disease. In a second aspect thereof, the present invention relates to a method for diagnosing the survival of a cancer patient, comprising identifying the amount and / or proportion of stable regulatory T cells in said cancer patient through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein a demethylation in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, is indicative of a stable regulatory T cell, and wherein an increased amount and / or proportion of stable regulatory T cells in said cancer patient is indicative for a shorter survival for said cancer patient. Furthermore, the present invention relates to an improved treatment of cancers based on the inventive methods, and a kit for performing the above methods as well as respective uses.

The present disclosure provides methods for measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in a sample containing cancer cells and lymphocytes obtained from a subject by labeling lymphocytes that show CD4 expression in the sample, then labeling lymphocytes that show OX40 expression in the sample, then labeling lymphocytes that show Foxp3 expression in the sample, then measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in the sample. Further provided are methods for determining the prognosis of a subject, predicting responsiveness of a subject having cancer to an OX40 agonist treatment, and methods for treating or delaying progression of cancer based on the number of CD4+ OX40+ Foxp3+ lymphocytes in a sample.

The invention discloses a method for detecting an immunosuppression function of human regulatory T cells. The method comprises the following steps: collecting peripheral blood for extracting a mononuclear cell; using fluorescein marked anti-CD4 and anti-CD25 antibodies for marking a cell surface antigen; using a fixing membrane-breaking agent for fixing the cell surface antigen; after breaking the membrane, using fluorescein marked anti-Foxp3 and anti-Helios antibodies for marking endonuclear transcription factor Foxp3 and Helios; and finally, using a flow cytometry for detecting CD4+CD25+FoxP3+Helios+Treg cell population. According to the method, the function of the regulatory T cells in the peripheral blood is directly analyzed in the manner of quickly detecting the expression condition of the children peripheral blood transcription factor Helios. According to the method, the anti-Helios, anti-CD4, anti-CD25 and anti-Foxp3 flow antibodies can be used for more quickly and accurately marking the peripheral blood Treg cells with higher immunosuppression function.

In one aspect the invention relates to a method of switching the phenotype of a target cell, said method comprising inducing lineage factor activity in said cell via a transgene. In another aspect, the invention relates to a method of switching the phenotype of a target cell, said method comprising introducing to said cell a genetic element capable of inducibly generating lineage factor activity, and inducing lineage factor activity in said cell. The invention also relates to methods of suppressing immune responses and methods of treating subjects.

The invention pertains to biomedical technique field, in particular to a TGF-beta induced regulatory T-cell and a synthesis method and the applications thereof. The regulatory T-cell of the invention is formed by combining two cytokines: TGF-Beta and IL-2, and obtained by extrinsically inducing CD4+ cells of autoimmune diseases sufferer, and is recorded as CD4++CD25+Foxp3+ regulatory T-cell, wherein FoxP3 is FoxP3 gene or protein. The regulatory T-cell of the invention can be taken as a medicine preparation that is used for treating the diseases of autoimmune diseases (such as SLE) sufferer.

A method for assessing risk of losing a transplanted organ by a patient having an episode of acute rejection of the transplanted organ is described. The method includes obtaining from the patient a cell sample from the transplanted organ or peripheral blood, determining a level of FOXP3 in the cell sample, and correlating the level with the risk of loss of the transplanted organ, wherein, compared to a control level, a significantly greater level of FOXP3 in the cell sample from the transplanted organ or a significantly lower level of FOXP3 in the cell sample from the peripheral blood correlates with a decreased risk of loss of the transplanted organ.

A method of identifying an antigen-specific regulatory T cell (Treg) from a subject is discussed wherein the method comprises quantitatively or qualitatively detecting co-expression of each of cell markers CD4, CD25 and CD134, or alternatively, N each of cell markers CD8, CD25 and CD137, as well as one or more cell markers selected from the group of Treg cell markers consisting of CD39, CD73, CD127, CTLA-4 and Foxp3 on a cell in a suitable lymphocyte-containing sample from the subject in response to exposure to a target antigen. Also discussed are methods of isolating and expanding the identified antigen-specific Treg population, which may permit antigen-specific Treg cell therapy.

Induction of tolerance to antigens by mucosal, preferably oral, delivery of the antigen in combination with an immunomodulating compound producing micro-organism is disclosed. More specifically, Foxp3+ and / or IL-10 and / or TGF-β producing regulatory T-cells are induced which are capable of suppressing undesired immune responses toward an antigen. The antigen is preferably delivered orally in combination with an immunosuppressing cytokine secreting micro-organism.

The invention relates to application of scutelloside in pharmacy. The scutelloside promotes a T cell to be transformed toward Treg with immunological suppression effect by up-regulating the expression of Foxp3; at the same time, the scutelloside inhibits Th17 with pro-inflammatory effect and inhibits vasculitis mediated by the Th17. A main mechanism of inhibting the Th17 of the scutelloside is to inhibit the amplification of the Th17 mediated by IL-6. At the same time, a further experiment proves that the scutelloside taken as a novel immunomodulator plays good therapeutic effect on treating lupus erythenlatosus nephritis and rheumatoid arthritis.

The invention discloses a polygene transfection tumor cell strain and a fusion vaccine thereof, as well as preparation methods. The cell strain comprises an Foxp3 gene and an A20 gene, and adopts the pancreatic cancer tumor cell line DSL6A / C1 of a rat as a transfection cell. The preparation methods of thepolygene transfection tumor cell strain and the fusion vaccine comprise the following steps: modifying the fusion vaccine of DSL6A / C1 cell and a dendritic cell of Treg by building over-expression Foxp3 and A20miRNA, so as to obtain a novel tumor vaccine which not only has a DC special function but also can express tumor antigen; adopting the fusion vaccine of the tumor cell and the dendritic cell which are modified through co-transfection of Foxp3-A20 to further enhance the anti-pancreatic cancer immunity effect. The fusion vaccine has not only a complete tumor antigen, but also the characteristic of an antigen presenting cell, and can effectively present an tumor antigen to a T lymphocyte, thereby stimulating an organism to generate a specific anti-tumor immunity response, being a new direction of tumor immunological therapy, providing a new method for curing tumor patients, and having a potential application value.

The invention belongs to the immunology field, in particular to a proteantigen molecule-Japanese blood fluke heat shock protein 60KDa (SjHSP60) which is derived from a blood fluke and is capable of increasing CD4 + CD25 + Foxp3 + regulatory T cells and application thereof. The SjHSP60 has a full-length amino acid sequence as shown in SEQ.ID.NO.1, has a series of identical or highly similar cross-reactive T cell epitopes with HSP60 infected by a host. After being used for mouse in vivo immunization or in vitro stimulus to mouse spleen and lymph gland cells, the SjHSP60 can obviously increase CD4 + CD25 + Foxp3 + Tregs. In practical application, the SjHSP60 can effectively relieve inflammatory symptoms and immunopathological effects caused by arthritis, thereby having wide prospects in the aspects of immunological suppression inducement and treatment of immunological diseases.

The invention provides a pancreatic cancer detection reagent, a pancreatic cancer detection kit, a pancreatic cancer detection device and application. The detection reagent comprises antibodies of anytwo or more of the following molecular markers, wherein CD3, CD4, CD8 and CD68 belong to a group A, CD11b, CD14, CD33, CD45RO, CD57, CD66b, CD163, FoxP3, LAG3, PD1, PDL1, TIGIT, panCK and TIM3 belongto a group B, and at least one molecular marker is selected from the group B. Detecting pancreatic cancer through the antibodies of two or more of the molecular markers provided by the invention hasthe advantages of high detection sensitivity and excellent specificity. Thus, the molecular markers are suitable for a multiple immunohistochemistry method to detect tumor microenvironment of a pancreatic cancer patient and are very advantageous, and consequently, whether the patient has a longer lifetime can be accurately predicted relatively, namely, prognosis is better.

Disclosed are methods of isolating and using a population of FOXP3+ regulatory T cells in a variety of preventative and therapeutic approaches to autoimmune diseases, graft-versus-host disease and transplant rejection.

The invention relates to application of a PDE9A inhibitor in preparation of products for increasing Treg (Regulatory cell) content, drugs for preventing and treating inflammatory bowel diseases as well as health care products, and relates to the field of medicines. The PDE9A inhibitor can improve mucus secretion of a mucous membrane in the intestinal tract with inflammatory bowel diseases, reducesecretion of TNF- alpha, IL-6, IL-17 and IL-12 / IL-23 pro-inflammatory factors, inhibit DC cell differentiation and migration, increase the proportion of Foxp3+Treg cells and promote the movement of CD4+CD25+Treg cells from the spleen and mesenteric lymph nodes into the colon, thereby inhibiting the inflammatory reaction of the intestinal tract and controlling occurrence and development of the diseases. When applied to drugs for preventing and treating inflammatory bowel diseases, the PDE9A inhibitor can effectively prevent, alleviate and treat the inflammatory bowel diseases; and furthermore,the health care products taking the PDE9A inhibitor as an active component can condition the intestinal tracts of patients suffering from inflammatory bowel diseases so as to control occurrence and development of the inflammatory bowel diseases.

A method for the treatment and / or the prevention of a disease or a symptom related to dysfunction of regulatory T cell immunomodulation includes administering to a subject in need thereof compositions that regulate regulatory T cell immunomodulatory function, in which the compositions may be prepared by contacting starting materials with phosphorylation pathway-related factors, the agonists or the antagonists thereof. The phosphorylation pathway-related factors are selected from: proto-oncogene protein PIM1 and the coding sequence thereof. The regulation is achieved by regulating the activity of regulators of regulatory T cells selected from the group: FOXP3, IL-2, GITR, CTLA4, and a combination thereof.

The present invention is directed to methods of identifying and enriching for viable Foxp3+ cells and the use of such cells. In particular, the present invention provides methods whereby viable Foxp3+ cells are isolated from a mixed population of cells; Foxp3+ cells being identifiable as those cells with relatively high forward scatter as assessed by a flow cytometer.

A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

A unique CD4+CD25+ regulatory T cell population develops from naive CD4+CD25− T cells during a TH1 polarized immune response (called TH1-TR cells). These TH1-TR cells can be generated by contacting naïve T cells with mature CD8α+ dendritic cells (DCs) that have been exposed to a TH1 polarizing adjuvant and, in some cases, an antigen of interest. The TH1-TR are identified by their expression of the cytokines IL-10 and IFN-γ, the transcriptional regulators T-bet and FoxP3, and the cell surface molecules CD4, CD25, CD69, CD44 and ICOS.

The invention discloses a use of lentinan in preparation of a drug for preventing diabetes type 1. The invention discloses a use of lentinan in preparation of a drug for adjuvant treatment on diabetes type 1. Lentinan is injected into the abdominal cavity of an NOD mouse with spontaneous diabetes type 1 and influence produced by lentinan with body immunity adjustment functions on NOD mouse diabetes incidence is observed. Lentinan reduces NOD mouse insulitis incidence through improving CD25, Foxp3 and T cell (Treg) quantity in NOD mouse spleen, pancreas and lymph nodes, inhibiting CD3, CD8 and cytotoxic T cell (CTL) activation and reducing proinflammatory cytokine secretion, improves a serum insulin level, keeps a blood sugar normal level, finally reduces NOD mouse diabetes type 1 incidence and improves an NOD mouse survival rate.

The invention relates to a culture solution of universal Treg cells and a culture method and application of the culture solution. The culture method of the culture solution of the universal Treg cellscomprises the following steps: S110, co-culturing CD4+ CD25+ Treg cells and hUC-MSCs according to a certain proportion for 48 h-72 h, and centrifuging to obtain supernatant; S220, preparing peripheral blood PBMC and plasma, inactivating the plasma, and centrifuging for later use; S330, adding cytokine, calcium ionophore, plasma obtained from S220 and a RPMI1640 culture solution into the supernatant obtained from S110 to prepare a Treg cell culture solution; S440, inoculating peripheral blood PBMC into the Treg cell culture solution prepared in S330 according to a certain density, and culturing for 48 h-96 h; S550, collecting cells, wherein the cell viability is greater than 90%, the cell expression of CD4+ CD25+ Foxp3+ Treg is greater than 65%, and CD4+ CD25+ Foxp3+ Helios+ Treg cells account for more than 90% of the cell expression of CD4+ CD25+ Foxp3+ Treg. The problems that Treg cell culture operation is complex and the period is too long are solved, and the problems that the content of CD4+ CD25+ Foxp3+ Helios+ Treg cells in peripheral blood is too low and Treg cell treatment cannot be implemented due to a patient with low quality of autologous Treg cells caused by the problemof diseases of the patient are solved.