83 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 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.

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 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.

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.

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.