33 results about "Regulatory T cell" patented technology

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.

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 is an activator of regulatory T cells, an inhibitor of activity of effector T cells, an inhibitor of activation of B cells, an inhibitor of humoral immunity, or a therapeutic or prophylactic agent for an autoimmune disease, containing a polypeptide including an amino acid sequence equivalent to an HLA-DR binding epitope of an AChR.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) or allograft rejection in subjects receiving donor cells. Also disclosed are methods enhancing regulatory T (Treg) cells for use in preventing GVHD. Also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the treated Treg cells. Also disclosed are enhanced Treg cells produced by the disclosed methods that have been engineered to express chimeric antigen receptor (CAR) polypeptide cells.

The present application relates to a binding molecule capable of specifically binding to Lrig-1 protein, which is a protein expressed on the surface of regulatory T cells. The binding molecule provided by the present application can inhibit the function of regulatory T cells, thereby effectively preventing, improving or treating cancer, especially solid tumors. In addition, compared with commercially available antibodies against Lrig-1, the binding molecule provided by the present application can more effectively target Lrig-1 protein and show excellent binding affinity.

This invention discloses an oral frameshift peptide neoantigen vaccine, its preparation method, and its application, relating to the field of biomedical technology. The preparation method includes: 1) synthesizing a sea urchin-like metal-organic framework (MOF) via a hydrothermal method using zinc ions and 3,3''-dihydroxy-2',5'-dimethyl-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid; 2) loading the sea urchin-like MOF with a frameshift peptide and a Toll-like receptor 9 agonist via electrostatic interactions and / or van der Waals forces to prepare the oral frameshift peptide neoantigen vaccine. This vaccine not only promotes antigen endocytosis and transcytosis via intestinal microfold cells by activating cyclin 42, but also alleviates immune tolerance mediated by the goblet cell-regulatory T cell immunosuppressive axis and activates specific CD8+. + T cells help prevent the development of Lynch syndrome-related colorectal cancer.

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.

Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and / or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin / granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and / or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.

Methods of producing immunosuppressive Treg cells by exposing Treg cells to microgravity are disclosed. The Treg cells may be obtained directly from a sample from a subject, or CD4+ T cells may be induced to become Tregs. Compositions comprising the Treg cells exposed to microgravity are disclosed. The compositions may comprise other cell types and / or other components, such as cytokines.

The present invention provides, among other things, methods of using IL-2 fusion proteins, comprising an IL-2 variant and an Pc region, to treat and / or prevent heart transplant rejections. Methods of treating heart disease or a symptom thereof, conditioning a subject for heart transplant, modulating immunosuppression, and selectively increasing regulatory T cells are also disclosed.

This invention discloses a sensitizer for PD-1 antibody drugs and its application, as well as an antitumor drug composition and its application. The sensitizer comprises dihydroartemisinin and niraparib, and the antitumor drug composition comprises dihydroartemisinin, niraparib, and a PD-1 antibody. This invention is the first to experimentally discover that dihydroartemisinin possesses a dual mechanism of action: "non-HRD-dependent PD-L1 upregulation" and "tumor-selective ferroptosis induction." This mechanism complements and synergizes with niraparib's "HRD-dependent PD-L1 upregulation + synthetic lethality" mechanism and the PD-1 antibody's "immune activation" mechanism. The antitumor drug composition formed by combining these three components can effectively reshape the tumor immune microenvironment, exerting a potent antitumor effect by upregulating PD-L1 expression in tumor cells, increasing the number of cytotoxic T cells, and inhibiting the proportion of regulatory T cells.

The invention relates to variants of interleukin-2 (IL2). In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted such that affinity for the βγ IL2 receptor complex (IL2Rβγ) is enhanced. In one embodiment, the human IL2 or functional variant thereof is further substituted such that affinity for the αβγ IL2 receptor complex (IL2αβγ) is reduced. In one embodiment, the polypeptide activates effector T cells over regulatory T cells. The invention also relates to polynucleotides coding for the polypeptides of the invention, host cells comprising the polynucleotides, pharmaceutical compositions comprising the polypeptides, polynucleotides or host cells, therapeutic or prophylactic methods of treatment using the polypeptides, polynucleotides, host cells or pharmaceutical compositions and medical preparations comprising the polypeptides, polynucleotides, host cells or pharmaceutical compositions.

The application discloses a targeted cytokine composition for immunotherapy and a preparation method thereof. The fusion protein comprises, from N-terminal to C-terminal, an anti-PD-L1 single-domain antibody, a hinge region, a double-mutated human IL-15, a hinge region, an anti-NKG2D single-domain antibody and a double-mutated human IgG1 Fc fragment. In vitro experiments show that the fusion protein can simultaneously bind to double targets, significantly promotes NKG2D-positive CD8-positive T cell proliferation and has weak effect on regulatory T cells, and presents synergistic effect in a tumor-immune cell co-culture system. In vivo pharmacodynamic research shows that in a humanized mouse model, the fusion protein significantly inhibits the growth of colon cancer, the number of CD8-positive T cell and NK cell infiltrations in the tumor is obviously increased, and the effect is better than that of non-targeting and single-targeting controls. The fusion protein provided by the application has long-acting circulation, tumor targeting enrichment and immune cell subpopulation precise regulation functions, and can be used for preparing an antitumor drug.

A chimeric antigen receptor targeting glycoprotein A repeat dominant protein (GARP) and its use in the treatment of cancers, including but not limited to breast cancer, bladder cancer, glioblastoma, leukemia, or other malignancies characterized by GARP+Treg, are disclosed.

This invention discloses a colitis nanovaccine based on OMV and RA@LP, composed of Escherichia coli outer membrane vesicle OMV and liposome-encapsulated retinoic acid nanoparticles. The outer membrane vesicle OMV is extracted from wild-type or attenuated Escherichia coli. The preparation method of the liposome-encapsulated retinoic acid nanoparticles is as follows: S1, prepare an organic mixture solution containing hydrogenated lecithin and retinoic acid; S2, add the organic mixture solution to an aqueous solution containing poloxamer 188 and sodium dodecyl sulfate, maintain the solution temperature above 80°C and stir to emulsify; S3, perform ultrafiltration or centrifugation washing on the emulsion obtained in step S2 to remove unencapsulated drug and residual solvent, obtaining a liposome-encapsulated retinoic acid nanoparticle suspension. The nanovaccine provided by this invention can effectively induce tolerant dendritic cells (DCs) and promote the differentiation of regulatory T cells (Tregs) by regulating the delivery sequence of antigen and adjuvant, causing them to home to the intestinal site, thereby inhibiting the intestinal inflammatory response.

The present disclosure provides novel isolated IL-2 fusion molecules that preferentially activate regulatory T cells (Treg) in vitro and in vivo. Further included are methods of making and using said novel fusion molecules to treat inflammatory and autoimmune diseases.

In some aspects, the disclosure relates to a method of treating a tumor in a subject in need thereof, the method comprising administering to the subject a KRAS inhibitor and a regulatory T cell (Treg) depleting agent. In some aspects, the disclosure further relates to a method of reducing the number of Treg cells (Tregs) in a tumor environment (TME) in a subject receiving therapy with a KRAS inhibitor, the method comprising administering to the subject a Treg depleting agent. In some aspects, the disclosure further relates to a method of treating a tumor in a subject identified as having an increased number of Tregs in a TME, or identified as having a spatial cell population comprising Tregs in a TME.

The present application relates to the field of cell therapy, in particular to a regulatory T cell targeting IL12RB1 and use thereof. The regulatory T cell provided by the present application comprises a P40 subunit or a mutant thereof. The present application uses a natural protein sequence, which can avoid the immunogenicity risk of antigens caused by scFv; and enables Treg cells to home to inflammatory sites and inhibit activated lymphocytes.

The invention relates to a multiwell plate, an electrotransfection system comprising the multiwell plate, and a corresponding method for delivering a biologically relevant cargo into immune cells, wherein the multiwell plate comprising a plurality of wells, wherein a plurality of hollow nanostraws project from a bottom of each well to a height of between 1.5 μm and 2 μm, and have an inner channel with a diameter of between 200 nm and 400 nm. In one embodiment, the immune cells are CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Treg), yδ T cells, macrophages, dendritic cells (DCs), or neutrophils. In one embodiment, the cargo is a polynucleotide, a polypeptide, a nucleoprotein, a polysaccharide, or a combination thereof. In another embodiment, the cargo is a plasmid, an mRNA, a miRNA, a polypeptide, a ribonucleoprotein, or a combination thereof.

This invention discloses a method for preparing regulatory T cell-derived functionalized reconstructed vesicles, comprising the following steps: obtaining and expanding high-purity human Treg cells; resuspending the Treg cells in buffer solution, adjusting the density, and pre-treating with ultrasound; then, using a liposome extruder driven by a constant-speed injection pump, sequentially passing the Treg cell suspension through polycarbonate filter membranes with pore sizes of 10 μm, 5 μm, 1 μm, and 0.4 μm at different pressures for stepwise reconstruction; subsequently, enriching and purifying the reconstructed vesicles by high-speed centrifugation, graded filtration, and ultracentrifugation. The Treg-RVs prepared by this invention have uniform particle size, high concentration, and completely retain the core immunomodulatory functions of parental Treg cells, effectively inhibiting T cell proliferation.

This invention relates to a sequential acupuncture and moxibustion treatment method for postherpetic neuralgia, belonging to the field of traditional Chinese medicine acupuncture technology. The method includes: first, selecting Ashi points and Jiaji points for acupuncture, retaining the needles for 30 minutes; immediately after, selecting Shenque (CV8) and Zusanli (ST36) points for gentle moxibustion, moxibustion at each point for 15 minutes, for a total duration of 30 minutes; treatment is given 3 times a week for 4 consecutive weeks. This invention, through the sequential "acupuncture first, moxibustion later" approach, allows acupuncture to quickly unblock meridians and regulate neurotransmitters, while moxibustion provides continuous warm stimulation to synergistically enhance immune regulation. It can significantly upregulate the proportion of peripheral blood regulatory T cells and the level of related anti-inflammatory cytokines, reversing the immune imbalance associated with neuropathic pain, thereby effectively relieving pain, improving the patient's quality of life and psychological state, and demonstrating good safety. This invention provides a standardized, effective, and mechanistic traditional Chinese medicine treatment method for postherpetic neuralgia.

The present invention provides compositions and methods for inhibiting the autoimmune component of neurodegenerative diseases and thereby providing a therapeutic effect to patients suffering from such diseases. The compositions and methods comprise immunosuppressive moieties, such as regulatory T cells (Tregs) and proteins expressed by Tregs coupled to a chimeric antigen receptor or that specifically bind to one or more glial cell markers. Therapeutically effective doses of the compounds for treating neurodegenerative diseases, including progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), chronic traumatic encephalopathy (CTE), and prion diseases, are disclosed.

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-β)) and regulatory T cells and / or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

There is provided herein a method for expanding human CD4−CD8− regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), preferably the DN Tregs are αβ-TCR+CD56− or alternatively γδ-TCR+.

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), helper, naïve, memory, or effector, for example.

This invention provides novel applications for Lentinctobacillus cosonis, including an IL-10 production inducer activator, an anti-inflammatory agent, a regulatory T cell production inducer activator, and an immunosuppressant for diseases with hyperimmune responses. [Solution] An IL-10 production induction activator containing at least one of the bacterial cells or bacterial cell treatment products of lactic acid bacteria belonging to Lentilactobacillus kosonis as an active ingredient, which activates the induction of interleukin-10 (IL-10) production in dendritic cells. Also an anti-inflammatory agent that activates the anti-inflammatory properties of the body. Also a regulatory T cell production induction activator containing at least one of the bacterial cells or bacterial cell treatment products of lactic acid bacteria belonging to Lentilactobacillus kosonis as an active ingredient, which activates the induction of regulatory T cell (Treg) production. Also an immune hyperreaction disease suppressant that suppresses diseases caused by excessive immune responses in the body by activating the induction of regulatory T cell production.

This article provides the medical use of CXCR4-enriched regulatory T cells in combination with ruxolitinib for the treatment of myelofibrosis or to improve symptoms of myelofibrosis in subjects who have poor response to ruxolitinib monotherapy.

This application relates to the field of pet bone repair, specifically to a nutritional supplement for pet bone repair and regeneration and its preparation method. The supplement comprises the following components in parts by weight: 5 parts non-denatured type II collagen, 10-15 parts hyaluronic acid, 20-25 parts chondroitin sulfate, 6-7 parts hydrogen phosphate, 3-4 parts vitamin D3, 15-20 parts glucosamine hydrochloride, 0.5-1 part manganese glycine, 0.5-1 part magnesium aspartate, and 5-6 parts ascorbate. This application utilizes non-denatured type II collagen to activate regulatory T cells, reducing the release of inflammatory factors and thus alleviating joint pain and swelling; simultaneously, Treg cells secrete growth factors to stimulate chondrocyte regeneration and matrix synthesis, repairing damaged cartilage structure; the other components, combined with non-denatured type II collagen, stimulate chondrocytes to synthesize proteoglycans and collagen fibers, enhancing joint lubrication and cushioning function.