156 results about "Activation cells" patented technology

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.

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 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.

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 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.

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.

HIV-1-related immune activation is not only associated with AIDS progression, but also with CD4+ after cART treatment. + Insufficient T cell recovery is a contributing factor. This invention focuses on nicotinamide adenine dinucleotide (NAD) precursors and their potential in modulating host immune cells against HIV-1. Treatment with nicotinamide mononucleotide (NMN) inhibits HIV-1 infection at the post-transcriptional stage by targeting ACH-2 and primary CD4 cells. + Viral production in T cells. On one hand, the NMN treatment preferentially reduces CD25. + CD4 + Intracellular HIV-1 p24 production in T cells. On the other hand, using in vitro, ex vivo, and in vivo models, NMN consistently inhibited the expression of late T cell activation markers, including CD25 and HLA-DR. Furthermore, NMN works by assisting the production of CD4+. + T-cell regeneration to improve the therapeutic efficacy of cART in HIV-1-infected humanized mice.

The present invention relates to the role of purinergic receptors and ATP in T cell activation and autocrine system signaling. In one embodiment, the present invention provides a method of preventing or treating diabetes by administering a therapeutically effective inhibitor of ATP to a subject. In another embodiment, the present invention provides a method of preventing or treating fibrosis by administering a P2X7R soluble fusion protein. In another embodiment, the present invention provides a method of preventing or treating graft rejection by administering an inhibitor of P2X receptor signaling.

The anti-CD40L / anti-CD28 bispecific antibody according to the present application comprises anti-CD40L scFv and anti-CD28 scFv, and thus does not exhibit a thromboembolic side effect, can exhibit an excellent effect of treating autoimmune diseases and / or graft versus host diseases while preventing a T cell activation effect caused by CD28 dimer formation, and can be used as a novel anti-CD40L / anti-CD28 bispecific antibody. In addition, excellent bispecific antibody physical characteristics can be shown.

The application provides an immunogenic epitope prediction method based on antigen presentation and immunogenicity feature fusion, comprising the following steps: extracting peptide segments and type I human leukocyte antigen protein features from an immunogenic epitope database by using a constructed feature extraction module; inputting the peptide segments and type I human leukocyte antigen protein features into a pre-trained antigen presentation prediction model to obtain an antigen presentation probability based on the antigen presentation prediction model; inputting the peptide segments, type I human leukocyte antigen protein features and antigen presentation probability information into an immunogenicity prediction model to realize fusion of antigen presentation and immunogenicity features, and obtaining an immunogenicity score representing a T cell activation probability of the peptide segments based on the immunogenicity prediction model, so as to realize prediction of the immunogenic epitope. The application improves the prediction accuracy of the immunogenic epitope.

The application belongs to the technical field of immunotherapy, and particularly relates to an antigen epitope peptide of a tumor cell high-expression antigen LY6K and application thereof. The technical problem to be solved by the application is to provide a new method for treating or clinically detecting a tumor high in LY6K expression. The technical scheme of the application is an antigen epitope peptide of a tumor cell high-expression antigen LY6K, the amino acid sequence of which is shown in SEQ ID No. 4. The application provides a LY6K antigen epitope peptide, and a pMHC complex or an antigen presenting cell directly loaded with the antigen epitope peptide can activate T cells. Therefore, the antigen epitope peptide can be applied to treatment or diagnosis of a tumor high in LY6K antigen expression.

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of lymphoma (e.g., a diffuse large B-cell lymphoma (e.g., a germinal-center B-cell-like or activated B-cell-like diffuse large B-cell lymphoma). The invention is based, at least in part, on the discovery that macrophage biomarkers are useful in methods of identifying, diagnosing, or predicting the therapeutic efficacy of treatment with an anti-CD79b immunoconjugate (e.g., polatuzumab vedotin) and an anti-CD20 antibody (e.g., obinutuzumab or rituximab).

The application provides anti-CD28 nanobodies and uses thereof, and belongs to the technical field of biotechnology. Specifically disclosed are several CD28-targeted nanobodies, coding sequences and expression vectors for producing the nanobodies, and application of the nanobodies in preparation of tumor treatment drugs. The nanobodies can not only specifically recognize and bind to CD28, laying a foundation for subsequent development of antibody conjugated drugs and multi-specific antibodies, but also can be combined with tumor antigen-targeted antibodies to form multi-specific antibodies, and the formed multi-specific antibodies significantly enhance the ability of activated T cells and the activity of killing tumor cells.

The invention relates to an activating composition comprising a cell, which may be any cell type used for cell therapy, wherein the cell is activated by a chemotherapy agent. Further, there is provided an activating composition comprising a supernatant of a composition comprising a cell, which may be any cell type used for cell therapy, wherein the cell is activated by a chemotherapy agent and wherein the supernatant is used as a therapy. The invention further provides methods for treating or preventing a disease or a condition comprising the use of the activated composition.

The present invention relates to an isolated antigen-binding protein, which comprises a CD3-binding moiety, wherein the CD3-binding moiety comprises amino acid sequences having at least 95% identity to heavy chain variable regions HCDR1, HCDR2 and HCDR3; the amino acid sequence of the HCDR1 is set forth in any one of SEQ ID NOs: 1 and 2; the amino acid sequence of the HCDR2 is set forth in any one of SEQ ID NOs: 3, 4 and 5; the amino acid sequence of the HCDR3 is set forth in SEQ ID NO: 6; and / or, the CD3-binding moiety comprises amino acid sequences having at least 95% identity to light chain variable regions LCDR1, LCDR2 and LCDR3; the amino acid sequence of the LCDR1 is set forth in any one of SEQ ID NOs: 7, 8 and 9; the amino acid sequence of the LCDR2 is set forth in any one of SEQ ID NOs: 11 and 12; the amino acid sequence of the LCDR3 is set forth in SEQ ID NO: 13, wherein the CD3-binding moiety can induce T cell activation.

The present invention relates to the field of adoptive immune cell therapy, in particular adoptive T cell therapy. The present invention provides a conversion receptor which is capable of effectively converting an immunosuppressive signal of TGF [beta], which is normally present in the hostile tumor environment of a solid tumor, into a co-stimulatory signal, thereby improving T cell activation, and which can be safely used in therapy. Also provided are nucleic acids encoding the transforming receptors, cells expressing the receptors and pharmaceutical compositions comprising the cells, in particular for the treatment of cancer or infectious diseases, such as adoptive T cell therapy by solid tumors.

The present invention generally relates to improved protease-activatable antigen-binding molecules that comprise an anti-idiotype-binding moiety which reversibly masks a CD3 antigen binding moiety of the molecule. In addition, the present invention relates to polynucleotides encoding such protease-activatable T cell binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the protease-activatable T cell binding molecules of the invention, and to methods of using the same, e.g., in the treatment of disease.