246 results about "Activation cells" patented technology

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

The invention provides application of a substance for detecting the ratio of lymphocyte subgroups in preparation of a reagent or a kit for diagnosis or auxiliary diagnosis of Graves disease, and belongs to the technical field of preparation of disease diagnosis reagents. A research shows that compared with a healthy sample, the proportion of B cells in a lymphocyte subpopulation of a to-be-detected sample is remarkably increased, the proportion of NK cells is remarkably reduced, the proportion of activated T cells is remarkably reduced, the proportion of memory T cells is remarkably reduced, the proportion of CD4 + memory T cells is remarkably reduced, the proportion of Th1 cells is remarkably reduced, and the proportion of Tc1 cells is remarkably reduced, so that the to-be-detected sample is a GD patient; the substance for detecting the ratio of lymphocyte subgroups is high in sensitivity and specificity when being used for diagnosis or auxiliary diagnosis of Graves disease.

Disclosed in the present invention are a targeted immunotolerance vaccine, a preparation method therefor, and use thereof. The present invention separately modifies a rheumatoid arthritis-related autoantigen peptide and CTLA4 Ig with DSPE-PEG (DP) to prepare a targeted formulation DP-antigen peptide and a targeted formulation DP-CTLA4, which are then mixed to obtain the vaccine. The vaccine described in the present invention, after intravenous injection, binds to albumin in vivo by means of DSPE, "hitchhiking" on albumin to target and enrich in inflammatory lesions, the spleen, the liver, and other tolerance-inducing sites, inhibiting T cell activation, and inducing anergy and apoptosis of rheumatoid arthritis autoantigen-specific T cells, thereby achieving immunotolerance treatment and prevention of rheumatoid arthritis.

This disclosure provides compositions and methods for the activation and expansion of human T cells or NK cells using soluble monospecific antibody complexes.

The invention discloses a time-space controllable T cell adapter based on a DNA nanostructure as well as a construction method and application of the time-space controllable T cell adapter, and belongs to the field of DNA nanotechnology. The T cell adapter comprises a six-spiral-bundle paper folding structure, and an internal functional layer and an external shielding layer which are assembled on the six-spiral-bundle paper folding structure; the six-spiral bundle paper folding structure is formed by assembling 63 staple chains and M13 in total; the internal functional layer comprises nucleic acid-antibody conjugates which are combined on four spiral extension sequences at the top and the bottom of the six-spiral bundle origami structure, and hand-in-hand palindromic sequences which are combined on two spiral extension sequences at the left side and the right side; the outer shielding layer comprises a C-chain modified serum albumin binding peptide and a chain I, and the chain I comprises a pH-responsive i-motif switch. The T cell adapter disclosed by the invention has the space-time control capability of pH response and the potential of inducing TCR clustering to enhance T cell activation, and has huge potential in the aspect of improving the safety and effectiveness of T cell immunotherapy.

The invention belongs to the field of biological medicine, and particularly relates to a CD3-LILRB4 bispecific antibody and application thereof. The invention provides a novel bispecific antibody with high activity and low toxicity, the bispecific antibody can be combined with CD3 and LILRB4 so as to promote T cell activation and effectively promote PBMC (peripheral blood mononuclear cells) to kill tumor cells, the bispecific antibody has good anti-cancer activity, and the bispecific antibody has the performance of reducing secretion of proinflammatory cytokines, is higher in safety, and can be applied to preparation of anti-tumor drugs. Good clinical application and drug development values are realized.

The application discloses a hybridoma cell strain secreting an anti-tilapia interleukin-2 monoclonal antibody and an application thereof, and the hybridoma cell strain 1C11F5 is preserved in the China Center for Type Culture Collection (CCTCC) on March 9, 2024, and the preservation number is CCTCC NO: C202470. The application can specifically identify the tilapia IL-2 protein and the lymphocyte group secreting IL-2, is helpful for further exploration of T cell activation and proliferation, and provides an important immunological tool for adaptive immune mechanism research of hard fish (such as tilapia and the like).

The present application relates to a kind of hydrolysis targeting chimera based on artificial antibody and its preparation method and application.The hydrolysis targeting chimera is composed of artificial gold antibody and molecule that can activate cell degradation mechanism, the artificial gold antibody is composed of gold nanoparticle and polypeptide coupled on the surface of gold nanoparticle, the molecule that can activate cell degradation mechanism is coupled on the surface of gold nanoparticle.The hydrolysis targeting chimera can simultaneously bind target protein and activate cell degradation mechanism, with the performance of strong specific recognition target protein, and high stability, orientation controllable.At the same time, the hydrolysis targeting chimera can also play the molecule of activation cell degradation mechanism, such as lysosome sorting signal motif, coupled on the surface, induce clathrin-mediated endocytosis, transport the complex of target protein and chimera to lysosome and degrade.The hydrolysis targeting chimera can play multi-mode cancer treatment effect by synergistic inhibition of tumor cell proliferation, invasion pathway and apoptosis activation.

A family of sulfonyl-azole compounds are described which include small molecule activators of phosphofructokinase-1, liver isoform (PFKL). The small molecule activators selectively form covalent adducts with PFKL, including particularly lysine 677 of the human PFKL. Also provided are methods for using the small molecule activators to activate PFKL, e.g., to provide increased glycolysis and / or T cell activation, to treat cancers and / or tumors, and / or to enhance fructose-1,6-bisphosphate (FBP) content in cells.

The present invention relates to multispecific antigen binding proteins that comprise an antigen-binding regions specific for a tumor-associated antigen (TAA), an antigen-binding region that specifically binds an epitope of a γδ T cell receptor (TCR), a γδ T cell-activating cytokine, and optionally, a γδ T cell co-stimulatory agonist. The γδ T cell-activating cytokine preferably is at least 5 one of an interleukin 21 receptor (IL21R) agonist and an interleukin 15 receptor (IL15R) agonist. The γδ T cell co-stimulatory agonist cytokine preferably is at least one of a 4-1BB agonist, a CD27 agonist and a GITR agonist. The multispecific antigen binding proteins of the invention specifically redirect and activate γδ T cell to lyse targeted tumor cells. The invention further relates to the use of such multispecific antigen binding proteins in the treatment of cancer, preferably a cancer 10 expressing the TAA.

The invention provides a three-specificity immune cell adapter-cytokine fusion protein for malignant tumor immunotherapy as well as a preparation method and application of the three-specificity immune cell adapter-cytokine fusion protein. The fusion protein comprises a first binding domain, a second binding domain and a cytokine structural domain which are covalently linked to form a single polypeptide chain or polypeptide compound. The first binding domain is specifically bound with a tumor associated antigen, and the target spot of the first binding domain comprises but is not limited to KK-LC-1, MSLN, HER2, Claudin18.2, Claudin6 and PSMA; the second binding domain is specifically bound with a CD3 protein complex on the surface of the T cell; the cytokine domain is IL2, IL15, IL12, IL21 or a functional variant thereof. The invention also relates to a nucleic acid molecule for coding the fusion protein, an expression vector and application thereof. The fusion protein can be used for immunotherapy of malignant tumors such as colon cancer, gastric cancer, breast cancer, liver cancer, lung cancer and cervical cancer, and has a good application prospect. The invention effectively solves the problems of insufficient T cell activation and limited killing in solid tumor immunotherapy in the prior art.

The present invention relates to compositions targeting epidermal growth factor receptors and methods of making and using the same, and particularly provides antibody binding domains for the differentiation cluster 3 T cell receptor (CD3), antibody binding domains for the epidermal growth factor receptor (EGFR), cleavable linker sequences, and protease activatable bispecific fusion proteins, a T cell adaptor, such as a protease, can be activated, as well as uses and methods of treatment.

This application relates to the field of tumor treatment technology, specifically to a drug combination and evaluation method for improving the sensitivity of MSS CRC to anti-PD-1 / PD-L1 therapy. The drug combination comprises vancomycin and an immune checkpoint inhibitor. Vancomycin is used to remodel the gut microbiota and reduce L-asparagine levels; the immune checkpoint inhibitor is used to activate CD8. + T-cell anti-tumor response. By combining vancomycin with immune checkpoint inhibitors, the antigen-presenting capacity of dendritic cells is enhanced, thereby increasing the sensitivity of MSS CRC to anti-PD-1 or anti-PD-L1 immunotherapy. This application focuses on the upstream initiation link of gut microbiota-metabolites-dendritic cells-immune activation, relieving the inhibition of dendritic cell antigen presentation by L-asparagine and enhancing CD8+. + T cell activation and tumor immune response enhance the sensitivity of MSS-type colorectal cancer to anti-PD-1 / PD-L1 therapy.

This disclosure relates to an antibody or fragment thereof comprising an antigen-binding domain capable of binding to a CDS protein or fragment thereof. This disclosure also relates to such antibodies that bind to CDS having an affinity optimized for inducing T cell activation but without being associated with excessive cytokine release and decreased tolerance. This disclosure also relates to methods for producing these antibodies and their therapeutic use.

Disclosed herein is a method of modifying a T cell during T cell activation comprising contacting the T cell with an inhibitor of prolyl hydroxylase. Also disclosed is a method of producing a chimeric antigen receptor (CAR) or T cell receptor (TCR) T cell comprising (i) modifying the T cell during activation of the T cell by contacting the T cell with an inhibitor of prolyl hydroxylase, (i) introducing a CAR or TCR transgene into the modified T cell, and (iii) harvesting the CAR or TCR T cell. In particular, the inhibitor of prolyl hydroxylase is a small molecule prolyl hydroxylase inhibitor, such as 1, 4-DPCA. The harvested CAR or TCR T cells can be used for adoptive T cell immunotherapy of cancer.

The invention relates to a method for detecting activation of specific T cells after tuberculosis infection and application of the method. Specifically, the invention provides a reagent combination for detection, and the reagent combination comprises an anti-CD4 antibody (CD4 antibody), an anti-CD154 antibody (CD154 antibody), an IFN-gamma detection antibody and a tuberculosis specific antigen. According to the method, through peripheral whole blood collection, PBMC cell separation, T cell activation (activation), activation termination (blocking), antibody labeling, membrane rupture, fixation, intracellular cytokine dyeing, flow cytometry detection and result analysis and judgment, the ratio of the expression IFN-gamma cells in the CD4 + CD154 + cells can be rapidly and accurately determined, and by combining an ROC curve and a constructed judgment standard, the content of the IFN-gamma cells in the CD4 + CD154 + cells can be determined, and the content of the IFN-gamma cells in the CD4 + CD154 + cells in the CD4 + CD154 + cells in the CD4 + CD154 + cells in the CD4 + CD154 + cells can be determined. And the sample to be detected is judged to be in a positive / negative / gray region, so that whether a patient is infected by the mycobacterium tuberculosis or not can be more accurately diagnosed, especially aiming at a whole blood sample from a special crowd.

The invention relates to an inducible chimeric co-stimulatory receptor (CCR) comprising an intracellular T cell activation dependent localization domain. The invention further relates to an immune cell expressing the inducible CCR, a nucleic acid molecule encoding said inducible CCR, and to a pharmaceutical composition, comprising said immune cell or said nucleic acid molecule. The invention further relates to a method of producing said immune cell and to a method of treating a malignancy, comprising providing immune cells expressing the inducible CCR to a patient in need thereof.

The invention discloses an amplification culture solution of TILs cells and a culture method thereof. The amplification culture solution comprises a complete culture medium, and an anti-BTLA antibody with the final concentration of 0.1-10 [mu] g / mL, penicillin with the final concentration of 50-500 [mu] g / mL, streptomycin with the final concentration of 50-500 [mu] g / mL, gentamicin with the final concentration of 10-100 [mu] g / mL and amphotericin with the final concentration of 1-50 [mu] g / mL are added into the complete culture medium. The anti-BTLA antibody component in the culture solution can relieve inhibition of BTLA on T cells by blocking combination of BTLA and a ligand HVEM of BTLA, so that the anti-tumor capability of TILs is enhanced; meanwhile, after the BTLA is combined with the ligand HVEM, T cell activation and proliferation can be inhibited, and rapid proliferation of TILs is promoted; the irradiation PBMC added in the TILs cell culture process can provide an activation signal for the TILs and drive rapid proliferation of the TILs cells.

The present invention addresses the problem of providing a novel treatment method for T-cell tumors that can induce cell damage in tumor cells and can be used in the treatment of a T-cell tumor of a subject with T-cell dysfunction. The present invention provides a therapeutic agent for a T-cell tumor of a subject with T-cell dysfunction, said therapeutic agent comprising a bispecific antigen-binding molecule, wherein the bispecific antigen-binding molecule includes (1) at least one section that specifically binds to a target tumor antigen expressed in T-cell tumor cells, and (2) at least one section that specifically binds to an antigen which is a normal T-cell-side target antigen and has a subtype, provided that the target tumor antigen expressed in T-cell tumor cells is not present in normal T-cells, or if present, the normal T-cells are substantially not activated when the bispecific antigen-binding molecule binds to the antigen that is present in the normal T-cells and is the same as the target tumor antigen, and a sufficient ratio of the subtype of the normal T-cell-side target antigen is present such that the normal T-cells are activated by the bispecific antigen-binding molecule binding to the normal T-cell-side target antigen and a sufficient number of activated T-cells for treatment of the T-cell tumor are provided.

Provided is a promoter having high activity in an activated T-cell. The promoter comprises, from 5′-end to 3′-end, a CMV enhancer, an IFNγ promoter, and a long terminal repeat sequence from human T-cell leukemia virus that are connected in sequence. The promoter exhibits greater activity in an activated immune cell than the existing promoters and is low in activity or inactive in other non-immune cells.

The invention relates to compounds that have been identified as CDK4 (cyclin-dependent kinase enzyme) inhibitors for the first time, for use as a medication, in particular, for the treatment of cancers e.g. those with overexpression of the enzyme CDK4, and to pharmaceutical compositions comprising same. Said compounds target the interaction interface between CDK4 and its activating cyclin, whereas those drugs already approved for the treatment of cancers with overexpression of the enzyme CDK4 target the ATP-binding site.

The present disclosure provides processes for genetically engineering T cells, such as primary CD4+ T cells and / or CD8+ T cells, for use in cell therapy that does not involve expanding the cells. In particular aspects, the provided processes successfully generate compositions of engineered T cells, such as containing populations of engineered T cells, that express a chimeric antigen receptor (CAR) within a shortened amount of time as compared to alternative engineering processes, such as processes that involve expanding the cells. In certain aspects, the provided processes successfully generate a composition of engineered T cells suitable for use in cell therapy within 4 days from when the process to stimulate or activate the cells is initiated. In some aspects, the resulting engineered cell compositions are composed of cell population that are less differentiated, less exhausted, and more potent than engineered T cell compositions generated by other means, such as by processes that involve expanding the cells. Also provided are compositions of T cells generated by the provided methods and their uses for treating subjects.

T lymphocytes play a key role in the immune response and their functions are intimately linked to metabolic programs. During immune responses, T cells undergo a metabolic reprogramming notably characterized by an increased aerobic glycolysis. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), we demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Conversely, Foxk1 overexpression in T cells enhanced their effector functions in a TCR-dependent manner. In CD8+ T cells, this effect also results into enhanced cancer cell killing capacity in vitro, and improved tumor rejection in vivo. Altogether, these results indicated that Foxk1 is a major regulator of T cell metabolism and thus, of T cell effector functions. Thus, the present invention relates to host immune cells engineered to overexpress a Foxk1 polypeptide and their use of the treatment of cancer.

The present application relates to a kind of universal preparation method for presenting tumor antigen and highly activated T cell exosome, belong to biomedical and immunotherapy technical field.The present application described method is first synthesized the tumor antigen specificity nano stimulant capable of activating dendritic cell, makes dendritic cell carry IFN-β, expresses specific tumor-related antigen and costimulatory molecule, to solve the problems, such as low antigen presentation efficiency, T cell activation deficiency and high cost of individualized treatment in the existing tumor immunotherapy method.Exosome is extracted from the supernatant of the above dendritic cell culture.The preparation method of the present application not only significantly improves the efficiency of exosome as antigen presentation carrier, effectively and specifically stimulates T cell, but also reduces the preparation cost, provides more effective general solution for tumor immunotherapy, has wide application prospect and clinical value.

This document relates to methods and materials for modulating (e.g., reducing) T cell activation (e.g., T cell proliferation, T cell effector functions, and / or cytokine secretion) using a TRAILshort polypeptide, a variant TRAILshort polypeptide, or a TRAILshort fusion polypeptide. For example, a TRAILshort polypeptide, a variant TRAILshort polypeptide, or a TRAILshort fusion polypeptide can be administered to a mammal in need thereof, e.g., a human with an autoimmune disorder, graft versus host disease, lichen planus or other disorder characterized by excessive T cell activation, to reduce excessive T cell activation (e.g., excessive T cell proliferation, excessive T cell effector functions, and / or excessive cytokine secretion).

The application discloses a kind of SNPs loaded engineered escherichia coli dual-response delivery systems and its preparation method and application, the preparation method includes the engineered escherichia coli of overexpressing Flt3L and TIM-3 scFv is co-incubated with NHS-PEG-CHO, obtain aldehyde functionalized escherichia coli;After activation SNPs is reacted with TFA-hydrazine, obtain hydrazine functionalized SNPs;Aldehyde functionalized escherichia coli and hydrazine functionalized SNPs are reacted;The delivery system of the application can rely on SNPs under laser stimulation Photo-thermal effect, photodynamic effect and generate a large number of ROS, efficiently induce tumor cells to occur immunogenic cell death (ICD), and by overexpressing Flt3L and TIM-3 scFv, activate DC cell and block TIM-3 path, restore DC, T cell function, realize the efficient synergy of photodynamic therapy+photothermal therapy+immunotherapy, and then reach the effective treatment of colorectal cancer.

The invention provides a therapeutic papilloma virus mRNA vaccine and application thereof. The invention provides mRNA molecules as shown in SEQ ID NO: 57-89, and the mRNA molecules can enhance T cell activation and immunogenicity, stimulate an organism to generate TH1 type cellular immune response and increase the tumor inhibition rate.

The present disclosure relates, at least in part, to compositions comprising microgels and / or granular hydrogels with tailored surface biochemical properties that can serve, e.g., as artificial antigen-presenting cells (aAPCs) to mediate, e.g., T cell activation and expansion. Such microgels and / or granular hydrogels can be used to manufacture T cells for adoptive therapy in cancer treatment and tissue regeneration, and can be configured to serve, e.g., as a readily tunable and modular system to enable both rapid T cell expansion and control over T cell phenotype. Some aspects of the present disclosure provide methods and compositions for fabricating microgels and / or granular hydrogels, and modulating the surface properties of microgels and / or granular hydrogels by functionalizing, e.g., via layer- by-layer coating.

This invention relates to the field of leukemia research, specifically disclosing an animal model of CAR-T therapy for leukemia complicated by cytokine release syndrome (CRS), its preparation method, and its application. The method for preparing the animal model of CAR-T therapy for leukemia complicated by CRS includes: obtaining CD19 CAR-T cells: peripheral blood mononuclear cell isolation, T cell magnetic bead sorting, T cell activation, lentiviral infection, and CAR-T cell expansion; constructing an animal model of CRS after high- and low-dose CAR-T infusion: implanting Nalm-6 cell line into living animals to induce leukemia tumor burden, obtaining living animals with leukemia tumor burden, and injecting CD19 CAR-T cell line into the living animals with leukemia tumor burden. This invention provides a novel application for the animal model of CAR-T therapy for leukemia complicated by cytokine release syndrome. By using severely combined immunodeficient mice and inoculating them with high- and low-burden tumor cells, and infusing different doses of CAR-T cells, this invention constructs an in vivo model that can simulate clinical CRS, providing research guidance for clinically exploring more effective interventions.

A fusion protein comprises (1) a first moiety that targets and orients the fusion protein to mitochondria inner membrane and (2) a second moiety that provides light-activated proton pump function when integrate into the mitochondria inner membrane. The fusion protein can be used for modulating hypoxia signaling in a subject, revitalizing cells, modulating T cell function, improving feed efficiency, prolonging lifespan and treating cancer.