400 results about "Regulatory T cell" patented technology

The invention discloses a cord blood-derived regulatory T cell amplification culture medium and a use method thereof, and relates to the field of animal cell culture and immune cell therapy, the culture medium is a serum-free culture medium, the culture medium is composed of a basic culture medium, a serum substitute combination, a combination of four cell factors, an immunosuppressor, an apparent stabilizer and an antioxidant, and all the components play a role synergistically; according to the use method, cell amplification is realized through a collaborative process of staged environmental regulation and targeted activation. According to the method, the problems of exogenous pollution and batch difference caused by dependence of a serum-containing system on cord blood-derived regulatory T cell amplification in the prior art are solved, the defect that a serum-free scheme is difficult to consider the amplification efficiency and the function stability at the same time is overcome, the cell amplification quality and the clinical application safety are guaranteed, and the method is suitable for large-scale clinical transformation requirements.

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a dual mutant transforming growth factor beta 1 (dmTGFB1) under control of a promoter sequence and a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TGFBR2. In certain embodiments, the cells further comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA; a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG; and insertion of sequence(s) encoding a regulatory T cell promoting molecule, and compositions and uses thereof.

Methods and compositions for treating fibrosis (e.g., cardiac fibrosis), or other conditions associated with inflammation and / or fibrosis are provided. Methods can include administering a nucleic acid encoding a sialic acid-binding immunoglobulin-type lectin 9 (Siglec-9) protein to a subject in need of fibrosis treatment, where the Siglec-9 protein is expressed by the nucleic acid in regulatory T (Treg) cells in the subject. Methods and compositions can include Treg cells that overexpress Siglec-9 to enhance the ability of Treg cells to target cells expressing amine oxidase, copper containing 3 (AOC3), including fibroblasts or myofibroblasts. In some embodiments, the enhanced Treg cells are targeted to myofibroblasts (e.g., cardiac myofibroblasts) with elevated expression of fibrotic genes.

The invention relates to the technical field of biology, in particular to a Treg cell amplification culture medium and a preparation method of Treg cells. According to the method for in-vitro amplification of the regulatory T cells (Treg) from peripheral blood, the amplification efficiency and purity of the Treg cells are improved, the culture cost is reduced, the culture period is shortened, and the problem of trophoblast cell residues in subsequent clinical application is solved.

The present invention relates to an engineered regulatory T cell (Treg) comprising a T cell receptor (TCR) which is capable of specifically binding to a myelin basic protein (MBP) peptide or variant or fragment thereof when the peptide is presented by a major histocompatibility complex (MHC) molecule. The present invention further relates to methods for providing an engineered Treg and to methods and uses of said engineered Treg and vectors and kits of vectors encoding said Treg.

The invention relates to a multifunctional silica plastid integrating chemotherapy, immunotherapy and gas therapy, and relates to a preparation method of the multifunctional silica plastid and application of the multifunctional silica plastid in tumor diagnosis and treatment. The schematic diagram is as shown in the figure, the membrane components comprise conventional phospholipid and complex lipid, a chemotherapeutic drug doxorubicin (DOX) entrapped on a hydrophilic core and Fe3 (CO) 12 entrapped on a hydrophobic core, and the chemotherapeutic drug can be adjusted according to needs and is suitable for broad-spectrum tumor treatment. The drug-loaded silica plastid can generate part of carbon monoxide in a tumor high-concentration hydrogen peroxide (H2O2) environment and release internally-loaded chemotherapeutic drugs. Under the action of ultrasound (US), the multifunctional silicon plastid can realize fixed-point release of chemotherapeutic drugs DOX and carbon monoxide at a tumor site, the enrichment and uptake of the drugs at the tumor site are greatly improved, in addition, the system is combined with the alphaPD-L1 antibody, the immunosuppressive PD-L1 / PD-1 axis can be blocked, T cells are recruited to attack tumors, meanwhile, the immunosuppressive regulatory T cells (Tregs) are reduced, and the tumor treatment effect is improved. The tumor inhibition can be enhanced; the pulmonary metastasis can be obviously reduced.

In some aspects, the present disclosure is directed to a method of treating a tumor in a subject in need thereof comprising administering a KRAS inhibitor and a regulatory T cell (Treg)-depleting agent to the subject. In some aspects, the present disclosure is further directed to methods of reducing the number of Treg cells (Tregs) in a tumor environment (TME) in a subject who receives a therapy with a KRAS inhibitor comprising administering a Treg-depleting agent to the subject. In some aspects, the present disclosure is further directed to methods of treating a tumor in a subject who is identified as having an increased number of Tregs in a TME, or as having a spatial cellular community comprising Tregs in a TME.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Provided is a fusion protein comprising IL-2 protein and CD80 protein. A fusion protein containing CD80 fragment, immunoglobulin Fc, and an IL-2 variant can activate immune cells, such as natural killer cells, and at the same time, can control immune cell regulatory activity of regulatory T cells. Therefore, a pharmaceutical composition containing the fusion protein as an active ingredient is very industrially useful in that such pharmaceutical composition can increase immune activity in the body, and thus can be effectively used against infectious diseases as well as cancer.

The invention provides agonistic TNFR2 antibodies and antigen-binding fragments thereof and encompasses the use of these antibodies as therapeutics to promote the proliferation of regulatory T cells (T-reg) for the treatment of immunological diseases. Antibodies of the invention can be used to potentiate the T-reg-mediated deactivation of self- and allergen-reactive T- and B-lymphocytes, and can thus be used to treat a wide variety of indications, including autoimmune diseases, allergic reactions, asthma, graft-versus-host disease, and allograft rejection, among others.

Provided is a fusion protein comprising IL-2 protein and CD80 protein. A fusion protein containing CD80 fragment, immunoglobulin Fc, and an IL-2 variant can activate immune cells, such as natural killer cells, and at the same time, can control immune cell regulatory activity of regulatory T cells. Therefore, a pharmaceutical composition containing the fusion protein as an active ingredient is very industrially useful in that such pharmaceutical composition can increase immune activity in the body, and thus can be effectively used against infectious diseases as well as cancer.

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a double mutant transforming growth factor [beta] 1 (dmTGFB1) under the control of a promoter sequence. In certain embodiments, the cells further comprise modifications of an endogenous nucleic acid sequence encoding TNFA, e.g., knockdown; modifications, e.g., knock-down, of an endogenous nucleic acid sequence encoding IFNG or IL17A; and insertion of sequences encoding regulatory T cell promoting molecules, and compositions and uses thereof.

Disclosed are: a method for producing a cell population containing regulatory T cells, the method comprising (1) culturing a cell population containing pluripotent stem cell-derived CD4+ T cells in the presence of at least one substance selected from the group consisting of a CDK8 and / or CDK19 inhibitor, a TNFR2 agonist, an mTOR inhibitor, and a TGF-βR agonist; a cell population containing regulatory T cells obtained by the method; and a medicine containing the cell population containing regulatory T cells.

Provided is a fusion protein, comprising IL-10 and a transmembrane domain, wherein the fusion protein is expressed on an immune cell, and the immune cell does not comprise a regulatory T cell. Also provided is a modified immune cell, comprising a fusion protein and an antigen recognition receptor, wherein the fusion protein comprises IL-10 and a transmembrane domain, and the immune cell does not comprise a regulatory T cell. Also provided is a use of the fusion protein and the modified immune cell in prevention and / or treatment of diseases.

Provided is a fusion protein comprising IL-2 protein and CD80 protein. A fusion protein containing CD80 fragment, immunoglobulin Fc, and an IL-2 variant can activate immune cells, such as natural killer cells, and at the same time, can control immune cell regulatory activity of regulatory T cells. Therefore, a pharmaceutical composition containing the fusion protein as an active ingredient is very industrially useful in that such pharmaceutical composition can increase immune activity in the body, and thus can be effectively used against infectious diseases as well as cancer.

To provide novel methods for expanding cell populations, such as regulatory T cells or central memory T cells, for research, diagnostic and, in particular, therapeutic purposes.SOLUTION: The present invention relates to in vitro-methods of expanding a population of cells such as lymphocytes, comprising contacting a sample comprising a population of cells with a multimerization reagent. The multimerization reagent has reversibly immobilized thereon (bound thereto) a first agent that provides a primary activation signal to the cells and optionally, a second agent that provides a co-stimulatory signal. The invention also provides multimerization reagents, kits, arrangements and an apparatus for expanding cells.SELECTED DRAWING: None

Lymphedema is characterized by the accumulation of protein-rich interstitial fluid, lipids and a significant inflammatory cell infiltrate in the limb. It causes a significant morbidity and is a common disabling disease affecting more than 250 million people worldwide, however there is no curative treatment for lymphedema. Here, the inventors found that dermolipectomies from patient with lymphedema exhibit inflamed gene expression profile compared to normal arm on same patient. After lipidomic analysis, the inventors identified severe decrease in arachidonic acid-derived lipid mediators generated by the 15-lipoxygenase (15-LOX) in lymphedematous arms. Using a mouse model of lymphedema, they reproduced the etiology of the human pathology including the loss of specialized pro-resolving lipid mediators that play essential roles in resolution of inflammation. This was associated with a lack of regulatory T cells (Treg) recruitment in the injured limb adipose tissue. Importantly, the inventors identified the lymphatic endothelial 15-LOX was responsible for the chemoattraction and transendothelial migration of Tregs. These results were confirmed by an aggravation of lymphedema and deterioration of the lymphatic network in an original transgenic mouse model in which ALOX15 gene is selectively deleted in the lymphatic system. Importantly, this was reversed by the injection of 15-LOX expressing lentivectors. These results provide evidence that lymphatic lipoxygenase may represent a novel therapeutic target for lymphedema by serving as a mediator of Treg invasion into lymphedematous adipose tissue.

The invention belongs to the technical field of immunology, and particularly discloses an in-vitro preparation method and application of an induced follicular regulatory T cell iTfr.The in-vitro preparation method comprises the steps that mouse spleen single-cell suspension or healthy human peripheral blood is obtained, peripheral blood mononuclear cells are obtained, then initial CD4 + T cells are obtained through immunomagnetic bead sorting, and iTfr cells are obtained; then carrying out induced differentiation by using an antibody and a specific cytokine, and carrying out continuous stimulation and culture by adopting two different cytokine polarization conditions, so as to obtain the iTfr cell. The invention provides a method for preparing the iTfr cells in vitro, which is expected to obtain an enough number of induced follicular regulatory T cells, and provides an important tool and a treatment means for in vitro research of immune tolerance related diseases such as autoimmune diseases and organ transplantation.

Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Combinations of anti-ICOS antibodies and other drugs for immunooncology.

The present disclosure provides a method for in vitro expansion of cryopreserved cord blood-derived regulatory T cells (Tregs) with a high recovery rate, including the following steps: recovering the cryopreserved cord blood-derived Tregs after first expansion, and resuspending the cells with a serum-free medium; and adding a resulting suspension to an expansion culture medium, and conducting a second expansion culture, where a primary culture is conducted for 1 d to 2 d, then a subculture is conducted once every 1 d to 3 d, and a total culture time is 13 d or more. In the expansion culture medium, interleukin-2 (IL-2) is further added. The method of the present disclosure can achieve the second recovery and expansion of cryopreserved Tregs produced after the first expansion. Tregs produced after the second recovery and expansion can have a viability of 90% or more, and can be further expanded (such as third expansion and fourth expansion). The expanded cells can also be used for clinical treatment. Therefore, the method of the present disclosure greatly shortens the time for clinical patients to wait for Tregs, and can meet the clinical on-demand access requirement.

Therapeutic use and dosing regimen of anti-ICOS antibodies or antigen-binding fragments thereof for modulating the ratio between regulatory T cells and effector T cells, stimulating the immune system of patients, and / or treating tumours or cancers, as monotherapy or combination therapy, e.g., with anti-PD-L1 antibodies or antigen-binding fragments thereof.

The present disclosure generally relates to novel chimeric antigen receptors (“CARs”), modified regulatory T cells (“Tregs”) expressing such CARs and / or Tregs which are engineered to express neurodegenerative disease modifying molecules, e.g., which express molecules which prevent oxidative / inflammatory activity, or which promote neuronal growth / survival such as nerve growth factors or non-classical neurotrophic factors. The present disclosure also generally relates to compositions containing such modified Tregs, and methods of use thereof as therapeutics, in particular for treating and preventing neurodegenerative diseases and symptoms associated with therewith, and / or for slowing the onset of such neurodegenerative diseases, particularly in persons at risk because of genetic factors or in persons exhibiting early signs of developing such a neurodegenerative disease.

In some aspects, the present disclosure is directed to a method of treating a tumor in a subject in need thereof comprising administering a KRAS inhibitor and a regulatory T cell (Treg)-depleting agent to the subject. In some aspects, the present disclosure is further directed to methods of reducing the number of Treg cells (Tregs) in a tumor environment (TME) in a subject who receives a therapy with a KRAS inhibitor comprising administering a Treg-depleting agent to the subject. In some aspects, the present disclosure is further directed to methods of treating a tumor in a subject who is identified as having an increased number of Tregs in a TME, or as having a spatial cellular community comprising Tregs in a TME.

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 present disclosure describes methods of specifically modulating the activity and / or number of regulatory T (Treg) cells within a tumor in a subject. Such methods may be used to reduce the number of regulatory T cells within a tumor in a subject, as well as to inhibit tumor growth in a subject with cancer without eliciting an autoimmune response. This method relies on the inhibition of CD36 or PPARbeta.

The present disclosure discloses IL-2 mutants and uses thereof. More specifically, the disclosure provides IL-2 mutants and corresponding fusion proteins, conjugates, nucleic acid fragments, vectors, host cells, methods for preparing the mutants or fusion proteins, IL-2 mutants or fusion proteins prepared according to the methods, pharmaceutical compositions, pharmaceutical uses, methods for treating diseases, and methods for preferentially stimulating regulatory T cells. Compared to wild-type IL-2, the IL-2 mutants of the present disclosure have higher Tm values and improved stability; alternatively, the IL-2 mutants of the present disclosure have an increased yield or changed binding activity to the IL-2Rβγ complexes compared to wild-type IL-2.

The application of phlorizin in the medicine for treating and / or preventing lupus nephritis, the molecular formula of phlorizin is C 21 H 24 O 10 , the application promotes the differentiation of regulatory T cells (Treg) by applying phlorizin to up-regulate the PI3K / Akt signal pathway, thereby reducing the symptoms of lupus nephritis, and provides an effective treatment method with less side effects. In the application, the traditional Chinese medicine monomer phlorizin can effectively promote the differentiation of Treg cells, and compared with compound traditional Chinese medicine, the use of single component has more advantages in drug efficacy control and efficacy evaluation. In addition, phlorizin is widely sourced, low in cost and non-toxic, and is very suitable for long-term treatment of lupus nephritis.

The present invention relates to antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and / or expand T effector cell populations or function. For example, antibodies of the invention include antagonistic TNFR2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.

To provide a cell proliferation system, proliferation method, control method, and culture medium bag capable of proliferating various adherent cells and suspension cells. [Solution] Cells are grown in a bioreactor and activated by an activator (e.g., a soluble activator complex). The nutrient supply and gas exchange functions of an automated closed cell proliferation system make it possible to seed at, for example, a low seeding density. By manipulating the parameters of the cell growth environment, cells are placed in specific locations within the bioreactor for efficient exchange of nutrients and gases. System parameters are adjusted to shear any cell colonies that may form during the proliferation phase. Metabolic concentrations are controlled to improve cell growth and viability. Cell retention within the bioreactor is controlled. In some embodiments, the cells include T cells. In other embodiments, the cells include a T cell subpopulation, for example, regulatory T cells (Tregs).