205 results about "Treg cell" patented technology

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

A redirected Treg cell is endowed with specificity toward a selected target antigen or ligand. The cell contains a chimeric receptor polypeptide that is expressed in a single, continuous chain, with an extracellular recognition region displayed on the surface of the cell, a transmembrane region and an intracellular signaling region. The extracellular recognition region is specific for the selected target antigen or ligand. The intracellular signaling region includes a combination of T-cell signaling polypeptide moieties, which combination, upon binding of the extracellular recognition region to the selected target antigen or ligand, triggers activation of the redirected Treg cells to cause suppression of T-cell mediated immunity. Such redirected Treg cells may be used to suppress undesired activity of T effector cells thereby mediating an immune or inflammatory response. They are particularly useful in treating T effector cell-mediated diseases, such as inflammatory bowel disease, transplant rejection and GVH disease.

Species of human-derived bacteria belonging to the Clostridia class have been shown to induce accumulation of regulatory T cells (Treg cells) in the colon and suppress immune functions. Pharmaceutical compositions containing these bacteria can be used to prevent and treat immune-mediated diseases such as autoimmune diseases.

This application relates to a method for generating an improved immune response in a host. The method involves the step of administering a vectored vaccine in the presence of an agent that impairs Treg cell function.

The invention provides a humanized PD-L1 tumor cell line MC-38-hPD-L1, a builtanimal tumor model with the same and a method for constructing the humanized PD-L1 tumor cell line. The method particularly includes knocking out animal-origin PD-L1 by the aid of CRISPR-CAS9; carrying out amplification and cultivation to obtain knocked-out cell banks; extracting DNA (deoxyribonucleic acid) and carrying out PCR (polymerase chain reaction) amplification; recycling and cloning amplification products; carrying out over-expression on human-origin PD-L1 in MC-38 cell lines of mPD-L1 KO by the aid of lentivirus systems; packaging lentivirus and screening Puromycin to obtain the humanized MC-38 cell line of PD-L1. The humanized PD-L1 tumor cell line, the animal tumor model and the method have the advantages that as shown by results, high killing efficiency and multiplication capacity are obviously presented by tumor infiltration CD8 T lymphocytes after antibody treatment is carried out, tumor infiltration Treg cells can be obviously inhibited after antibody treatment is carried out, and accordingly the method is proved to be effective and feasible from the aspect of molecular mechanisms.

The invention discloses culturing, freezing and recovering methods of an activated lymphocyte with CD3+CD8+as major, which can solve problems that a patient needs carrying out blood sampling for many times caused by continuously utilizing the activated lymphocyte with CD3+CD8+as major. The method comprises the following steps of: (1) contacting the extracted lymphocyte of the peripheral blood with IL-2, IL-15, an anti-CD3 antibody and an anti-CD28 antibody, so as to amplify the activated lymphocyte with CD3+CD8+as major; (2) freezing and storing the activated lymphocyte; and (3) recovering the activated lymphocyte. The activated lymphocyte cultured via the method disclosed by the invention has clear components, and comprises few CD4+CD25+Treg cells and more CD8+T lymphocyte; feedback time and frequency of the activated lymphocyte can be adjusted according to other treatments for a patient, such as a radiotherapy or a chemotherapy, so that diseases, such as tumor, infectious diseases and immunodeficiency can be treated well.

A method for generating a population of functional regulatory T cells (T_REG-cells), which are a subset of the T cell lineage having the ability to actively suppress immune activation and maintain peripheral immune tolerance, is described. The method comprises the steps of first culturing haemopoietic stem cells (HSC) and/or haemopoietic progenitor cells in the presence of a Notch ligand that supports T cell differentiation, and then isolating T cells having a T_REG-cell surface marker phenotype. A suitable source of HSC is cord blood (CB) and a suitable culture medium is OP9 cells engineered to express the Notch Ligand Delta-Like 1 (DL1) (OP9-DL1 cell line). Examples of T_REG-cell surface marker phenotypes are CD4+CD25+, CD45RO+, CD45RA+, CD127_LOW−, LAG-3 and/or CD39+.

The invention relates to an anti-CCR8 monoclonal antibody and an application thereof. The invention discloses the anti-CCR8 monoclonal antibody. The antibody has a function of blocking binding betweenCCR8 and a ligand thereof, and the monoclonal antibody specifically targets Treg cells infiltrated in tumor tissues and having immunosuppressive activity, but does not target inflammatory the Treg cells and non-Treg type T cells. Compared with other targeting broad-spectrum Treg cell antibodies, the therapeutic antibody targeting CCR8 has better safety and effectiveness, so that the antibody is particularly suitable for immunotherapy of tumors.

The present invention provides binding molecules that specifically bind to GITR, e.g., human GITR (hGITR), on T cells and dendritic cells. Binding molecules of the invention are characterized by binding to hGITR with high affinity, in the presence of a stimulating agent, e.g., CD3, are agonistic, and abrogate the suppression of Teff cells by Treg cells. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such binding molecules. Methods of using a binding molecule of the invention to detect human GITR or to modulate human GITR activity, either in vitro or in vivo, are also encompassed by the invention.

The invention relates to a preparation method of CIK (Cytokine Induced Killer) cells with high proliferation capacity, high cytotoxic activity and high survival rate. The preparation method comprises the steps of: (1) sorting and removing CD4<+>CD25<+>Treg cells of peripheral blood mononuclear cell to obtain CIK pre-cells; (2) cultivating the CIK pre-cells in a cell culture fluid containing 100ng/ml of PHA, 100ng/ml of IL-6 and 10ng/ml of PGE2 for 24h; (3) transferring the CIK pre-cells to a cell culture bottle coated with 1microgramme/ml of CD3 monoclonal antibody, and adding 1000U/ml of IFN-gamma for cultivating for 48h; (4) adding 1000U/ml of IL-2 and 100ng/ml of IL-1alpha for cultivating for 4 days; and (5) adding 1microgramme/ml of insulin to continuously cultivate for 7-14 days. The invention further provides associated CIK cells, a method for inhibiting the peripheral blood mononuclear cell to be differentiated to the CD4<+>CD25<+>Treg cells and a method for promoting the proliferation of the CIK cells. The preparation method of the CIK cells provided by the invention is skillful in design, and the tumor killing cells-CIK cells prepared have stronger proliferation capacity, higher cytotoxic activity and better tumor killing efficiency, so that the clinical efficacy is improved, and the preparation method is appropriate for wide application in a large scale.

The invention discloses recombinantly-expressed Akkermansia membrane protein Amuc_1100 and an application thereof. The invention recombinantly expresses the Akkermansia membrane protein Amuc_1100, through animal experiments, we find that oral administration of the Akkermansia membrane protein Amuc_1100 can significantly improve the body weight of mice, increase colon length and crypt depth, and activate proliferation of intestinal stem cells to protect mice from colitis damage. Isolation of lymphocytes from the lamina propria of the colon shows that the proportion of Treg cells is significantly up-regulated and that of Th17 cells is significantly down-regulated, proving that Amuc_1100 can restore colon damage by adjusting the proportion of immune cells Treg/Th17. Therefore, the protein isexpected to be developed into a protein product for preventing or treating colitis.

A method to treat an autoimmune disease is provided. The method involves administration of interleukin-15 receptor (IL-15R) agonists in an amount effective to ameliorate a symptom of the autoimmune disease. The invention also involves a method to treat an autoimmune disease by ex-vivo expansion of CD44+CD122+Kir+ CD8+ Treg cells and administration of the CD44+CD122+Kir+ CD8+ Treg cells. Compositions comprising CD44+CD122+Kir+ CD8+ Treg cells are also provided. Methods for stimulating an immune response to an antigen are also provided.

The invention discloses application of ginsenoside Rh2 and particularly verifies that ginsenoside can be applied to preparation of inhibitors for inhibiting Treg cells or preparation of compositions for preventing and/or treating tumors with Treg cells increased. The ginsenoside Rh2 is capable of improving balance of T cells in human bodies by inhibition of the Treg cells, autoimmunity can be further enhanced, and accordingly an anti-tumor effect or an immunodeficiency disease improvement effect can be achieved.

The present invention provides methods and compositions for expanding Treg cells ex vivo or in vivo using one or more conjugates comprising a costimulatory moiety that stimulates at least one of three signals involved in Treg cell development and/or using dendritic cells pulsed with antigens and modified to display TGF-beta, or hematopoetic stem cells or bone marrow cells modified to display TGF-beta. The methods and compositions are useful, for example, in the treatment and prevention of autoimmune disease, including Type 1 diabetes and in preventing foreign graft rejection, as well as to establish mixed chimerism, induce tolerance to autoantigens, alloantigens or xenoantigens, beta cell regeneration, prevention of foreign graft rejection, and treatment of a genetically inherited hematopoietic disorder.

The present invention provides materials and methods related to culturing stable Treg cells or in vivo expansion of stable Treg cells, the cells made by the methods, treatments for various inflammatory/autoimmune pathologies and transplant/graft rejection, and related materials. Ex vivo induction and expansion of the stable Tregs is described, including use of inducing compositions, such as certain mAbs and other compounds, along with expansion medium comprising IL-2. In vivo expansion of stable Treg cells and treatments for various inflammatory/autoimmune pathologies and transplant/graft rejection are described, including the use of mAbs and their variants.