345 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.

Methods for selecting a cancer patient for immunotherapy comprise establishing a total passenger gene mutation burden from a tumor of a cancer patient, generating a background distribution for the mutational burden of the tumor, normalizing the total passenger gene mutation burden against the background distribution, and categorizing the cancer patient as an immunotherapy responder when the total passenger gene mutation burden is greater than the mean of the background distribution. When the cancer patient is an immunotherapy responder, the patient may be administered an immunotherapy regimen that comprises activation / inhibition of T cell receptors that promote T cell activation and / or prolong immune cytolytic activities.

A viral particle. The surface of the viral particle comprises a T cell activation primary signaling molecule and a T cell activation secondary signaling molecule; the envelope glycoprotein of the viral particle is subjected to a first mutation, so that the receptor binding ability of the viral glycoprotein is weakened or lost with respect to its receptor binding ability before the first mutation; and the envelope glycoprotein of the viral particle can also be subjected to a second mutation, so that the viral particle has enhanced resistance to complement-mediated inactivation or is not subjected to complement-mediated inactivation. The viral particle has improved specificity for targeted activation, stimulation and transduction of non-activated T cells, and is thus more applicable for the preparation of CAR-T cells in subjects.

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.

Provided are a construct targeting 4-1BB and a use thereof. The provided construct comprises an antigen-binding fragment targeting 4-1BB, wherein the amino acid sequence of the heavy chain variable region is as shown in positions 1-114 of SEQ ID No. 3 or positions 126-239 of SEQ ID No. 6, and the amino acid sequence of the light chain variable region is as shown in positions 1-107 of SEQ ID No. 4 or positions 1-107 of SEQ ID No. 6. The construct further comprises an antibody targeting MSLN, forming a bispecific antibody. The provided bispecific antibody has a good T cell activation effect, and also exhibits a good in vitro tumor cell killing effect and in vivo tumor inhibition effect. Thus, the provided bispecific antibody has important significance and application potential for preparing targeted antibody drugs.

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.

The invention belongs to the field of biotechnology and medical technology, and discloses application of tumor-associated macrophages with high expression of SLC16A10 in prognosis diagnosis and treatment of colorectal cancer. According to the invention, colorectal cancer single-cell transcriptome sequencing data analysis before and after anti-PD-1 treatment is carried out in the earlier stage; the tumor-associated macrophage subgroup with high expression of the SLC16A10 is enriched in a response group after colorectal cancer anti-PD-1 treatment, and the prognosis of a colorectal cancer patient with high expression of the SLC16A10 is good. Knock-down of the SLC16A10 leads to reduction of expression of the macrophage M1 type marker, and activation and toxicity of co-cultured T cells are reduced. The SLC16A10 promotes T cell activation and weakens immunosuppression on T cells, so that colorectal cancer anti-PD-1 treatment response is caused. The research explains the influence and mechanism of the macrophage SLC16A10 on colorectal cancer anti-PD-1 treatment, and provides a new strategy and theoretical basis for immunotherapy of colorectal cancer.

A fermentation process is disclosed that produces an immunomodulatory product. The process includes combining a source of starch, a source of sugar, and a source of a trace mineral with probiotic microorganisms and fermenting aerobically and anaerobically, thereby producing an immunomodulatory product. Turmeric is added before or after fermentation. The immunomodulatory product is also disclosed. Also provided are uses of the immunomodulatory product, such as to decrease inflammation in a subject. These methods can include increasing function of natural killer cells, decreasing T cell activation, altering CD69 expression on immune cells, and / or altering cytokine expression in a subject.

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.

The present invention provides a method for culturing immune organoids and its application. The present invention cultures immune organoids by isolating lung-infiltrating lymph nodes and evaluates the level of mucosal immune response produced against influenza virus. By adding components such as BAFF and IL-2 to the cell culture medium and using the air-liquid interface method to three-dimensionally reconstruct immune cells derived from lung-infiltrating lymph nodes, immune organoids with a lymphoid structure are formed. These immune organoids can more realistically reflect the level of local immune response in the lungs and better retain various immune cells. At the same time, T cells are activated, enhancing their helper effect on B cells; the time for B cells to differentiate into plasma cells and mature is greatly shortened, and the efficiency of detecting and evaluating the immunogenicity of viral antigens is improved.

The invention provides a preparation method of efficient activated NK cells, and belongs to the technical field of NK cell culture, and the preparation method comprises the following steps: S1, centrifuging whole blood, removing upper plasma to obtain a cell part, and diluting with a reagent I to obtain a cell diluent; s2, adding the cell diluent obtained in the step S1 into a centrifugal tube filled with a lymphocyte separating medium, centrifuging, sucking a middle mononuclear cell layer, and cleaning with a reagent II for multiple times to obtain target cells; s3, inoculating the target cells obtained in the S2 into a cell culture dish or a cell culture bottle, adding a lymphocyte basal culture medium and IL-2, activating the NK cells according to a traditional culture method, adding stem cell source exosomes on the seventh day of activated culture of the NK cells, adding the stem cell source exosomes once every three days later, continuously culturing to the 12th-17th day, and collecting to obtain the activated NK cells. The tumor killing effect is enhanced, and meanwhile the immune function of NK cells is adjusted.

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 present invention relates to a T cell activation inhibiting factor (VISTA) protein or mRNA containing a V-type immunoglobulin domain, as a diagnostic marker selected for treatment of a patient with an autoimmune disorder, and as a means for monitoring the success of treatment of an autoimmune disorder. The present invention relates to methods for patient selection and treatment monitoring, to combined diagnostic and therapeutic applications for determining VISTA protein and / or mRNA in a patient sample, and to diagnostic kits suitable for use in the methods of the invention.

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 present disclosure describes technologies for improving a T cell manufacturing process Specifically, upregulating low-density lipoprotein receptor (LDL-R) expression on a T cell surface. The described technologies are particularly suitable in manufacturing processes using of non-activated T cells in a transduction step.

The invention relates to the technical field of immunology and biology, in particular to a light chain variable region and a heavy chain variable region of a rabbit anti-canine CD3E monoclonal antibody and application of the light chain variable region and the heavy chain variable region. The rabbit anticanine CD3E monoclonal antibody is successfully developed, and the antibody can be applied to experiments such as ELISA (enzyme-linked immunosorbent assay), flow cytometry, immunohistochemistry, stimulation of canine T cell activation and the like. Meanwhile, after being transfected to the surface of a tumor cell, the T cell can be promoted to kill the tumor. The development of the antibody provides a basic tool for detection and subsequent tumor immunotherapy. Meanwhile, the problems of low affinity, poor antigen specificity and the like of a traditional antibody are solved, the performance of the antibody is improved, and the application scene of the antibody is expanded.