308 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.

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.

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.

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.

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).

The present invention relates to epitopes of leucine-rich immunoglobulin-like domain 1 (Lrig-1), an antigen present on the surface of regulatory T cells, and antibodies or antigen-binding fragments that specifically bind thereto.

The present disclosure relates to isolated agonist anti-IL18R antibodies, or fragments thereof, which selectively inhibits tumor-associated regulatory T cells. The disclosure also relates to isolated nucleic acid comprising sequences encoding the antibodies or fragments thereof. The antibodies and fragments thereof can be used for the prevention and / or treatment of cancer.

The application discloses application of a small-molecule drug indisulam in preparation of a drug for treating autoimmune diseases, and further verifies safety of the molecule, long-term continuous use of the drug does not cause weight loss of animals, and weight change has no difference with normal control mice; tissue sections of multiple organs show that the drug has no obvious toxic side effects on each organ. In addition, the drug can promote differentiation of regulatory T cells, but does not affect functions of other immune cells. Therefore, the drug is used for treating autoimmune diseases, and good effect is found.

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.

Disclosed are a method for producing a cell population in which regulatory T cells have proliferated, including (1) culturing a cell population containing CD4+ T cells derived from pluripotent stem cells in the presence of IL-4 and a TGF-βR agonist, a cell population containing regulatory T cells obtained according to the method, and a medicine containing the cell population containing regulatory T cells.

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.

Disclosed are tolerogenic compositions useful for inducing a tolerogenic immune response against a CRISPR-Cas effector polypeptide in a subject. The tolerogenic composition can comprise a) one or more microparticles, b) one or more regulatory T cell (Treg) stimulants encapsulated within each microparticle, and c) a CRISPR-Cas effector polypeptide or an immunogenic fragment thereof, or a fusion polypeptide comprising a CRISPR-Cas effector polypeptide or an immunogenic fragment thereof. The tolerogenic composition can comprise a) a soluble microneedle array, b) one or more agents that promote the differentiation of tolerogenic DCs in the soluble microneedle array, and c) a CRISPR-Cas effector polypeptide or an immunogenic fragment thereof, or a fusion polypeptide comprising a CRISPR-Cas effector polypeptide or an immunogenic fragment thereof.

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 invention discloses a novel aporphine compound, its preparation method and applications, and its structural formula is shown as follows. The name of the novel aporphine compound is 2-methoxy-9-hydroxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline (III 11 ). In the present invention: ① By using the computer-aided drug design method in the forefront field of pharmacy, this compound is designed according to the binding requirements of the drug action target; ② This compound is synthesized from 3-methoxyphenethylamine and 2-bromo-5-hydroxybenzaldehyde, and its preparation method is simple; ③ This compound is an aryl hydrocarbon receptor (AhR) agonist and an inducer for the generation of regulatory T cells (Treg cells), and can be used for the prevention and treatment of immune inflammation and related diseases. ④ This compound shows good plasma protein binding rate and bioavailability, and has good prospects for drug development. #imgabs0#

The invention relates to the technical field of medicines, and discloses a bifidobacterium longum strain GZBAI 01 and application thereof in degradation of benzoic acid and prevention or treatment of colorectal cancer. The strain is separated from faeces of healthy people, genomics identification is carried out, the metabolic profile of the strain is measured through metabonomics, the strain can convert benzoic acid with carcinogenic risk into protocatechuic acid with antitumor activity through unique metabolic capability, meanwhile, the function of regulatory T cells (Treg) in tumor drainage lymph nodes can be inhibited, differentiation of CD8 + T cells is promoted, and the tumor drainage lymph nodes can be inhibited. Therefore, the colorectal cancer is prevented through double ways of eliminating cancerogen and generating therapeutic agents. A colorectal cancer mouse model and a subcutaneous tumor mouse model verify that the strain can significantly reduce the number and volume of tumors, and shows a benzoic acid conversion effect superior to that of other strains in vivo and in vitro, and a new way is provided for prevention and treatment of colorectal cancer.