414 results about "Activation cells" patented technology

The invention relates to the technical field of cellular immunotherapy, in particular to application of efonidipine in preparation of a dendritic cell immunologic adjuvant. The invention provides an application of efonidipine in preparation of a dendritic cell immunologic adjuvant. It is found that efonidipine can promote maturation, migration and antigen presentation functions of DCs, and the homing ability of DCs and CD8 + T cell activation are remarkably improved. The activation aspect of efonidipine on DCs comprises improvement of expression of maturation indexes CD80, CD40 and CD86, expression of a migration index CCR7, activation of CD8 + T cells by antigen presentation and the like. The efonidipine used in the invention is a drug approved by FDA for clinical treatment of cardiovascular diseases, the application of the efonidipine in immunotherapy is found, new use of old drugs is realized, and the efonidipine has great economic value.

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.

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.

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.

The invention relates to an oncolytic virus VSV-aPDL1 / aCD137 for expressing a bispecific antibody as well as a construction method and application of the oncolytic virus VSV-aPDL1 / aCD137. The preparation method comprises the following steps: firstly designing aPDL1 / aCD137, then synthesizing an aPDL1 / aCD137 gene in vitro, amplifying the aPDL1 / aCD137 gene, connecting the aPDL1 / aCD137 gene to a pT7-VSV whole genome plasmid to obtain a virus whole genome plasmid pT7-VSV-aPDL1 / aCD137, and then co-transfecting the plasmid and a helper plasmid to a 293T cell to obtain the VSV-aPDL1 / aCD137 oncolytic virus. According to the present invention, the local anti-tumor immune response of the tumor is activated through the virus, the infiltration of the lymphocyte to the tumor tissue is recruited, the anti-PD-L1 / anti-CD137 bispecific antibody is expressed, the inhibition of the PD-1 / PD-L1 pathway on the T cell is blocked, and the inhibition signal of the PD-1 / PD-L1 pathway on the tumor cell surface is reversed into the CD137 signal of the activated T cell, such that the functional failure of the T cell caused by the PD-1 / PD-L1 pathway can be blocked, and the anti-tumor immune response of the tumor can be inhibited; the function and viability of T cells can be further improved, long-term immune surveillance on tumors is realized, and long-acting anti-tumor immune response is generated. Experiments show that the oncolytic virus can significantly prolong the lifetime of tumor-bearing mice, and a new strategy is provided for development of solid tumor 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 technical field of biological medicines, and particularly relates to an intracellular signal transduction region combination of a HER2-targeting chimeric antigen receptor and application of the intracellular signal transduction region combination. The chimeric antigen receptor containing the intracellular signal transduction region combination can keep the CAR positive rate, and can ensure the motility rate and the recovery amount of cells, so that the activity of CAR-immune cells is better ensured; immune cells of the chimeric antigen receptor containing the intracellular signal transduction region combination show significantly enhanced phagocytosis, killing and anti-depletion capabilities and T cell activation / activation level, and achieve stronger anti-tumor activity and stronger tumor wettability.

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.

The present invention relates to a method for rapidly preparing chimeric antigen receptor T cells (CAR-T), comprising the steps of: 1) contacting T cells or a cell population comprising the T cells with a stimulating agent to activate the T cells to obtain activated T cells or a cell population comprising the activated T cells; 2) contacting the activated T cell or a cell population comprising activated T cells with a nucleic acid molecule encoding a chimeric antigen receptor (CAR), thereby obtaining a CAR-T cell expressing the CAR; and (3) harvesting the CAR-T cells, culturing for 18-24 hours, harvesting after the culture is finished, and freezing or not freezing. According to the method, the total preparation time of the CAR-T cells is greatly shortened, and meanwhile, the amplification and tumor killing capabilities of the CAR-T cells are remarkably improved.

The invention belongs to the technical field of veterinary medicine, and provides a co-expressed recombinant porcine alpha and gamma interferon. The I-type interferon alpha and the II-type interferon gamma not only exert the anti-virus, anti-cell division and immune regulation effects of the interferon, but also can activate T cells and natural killer cells, and fully exert the multiple activities of the interferon. The two interferons are co-expressed in insect cells, the expression protein can be folded and then processed and modified, the structure of the expression protein is closer to a natural structure, the biological activity is high, the recombinant protein is easy to purify, the production scale is easy to expand, and live viruses or potential dangerous pathogens do not need to be treated, so that the production cost is reduced; by optimizing the production process and fermentation conditions, the quality and stability of the recombinant protein can be further improved.

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 present invention relates to the field of adoptive immune cell therapy, in particular adoptive T cell therapy. The invention provides a switch receptor capable of efficiently converting the immunosuppressive signal of TGFβ that is typically present in the hostile tumor environment of solid tumors into a co-stimulatory signal that improves T cell activation and that is safe to use in therapy. Also provided are nucleic acids encoding the switch receptor, cell expressing said receptor and pharmaceutical compositions comprising said cells, in particular, for treatment of cancer or an infectious disease, e.g., by adoptive T cell therapy of a solid tumor.

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 present disclosure generally relates to the preparation of biocompatible nanoparticles aimed to activate dendritic cells, in particular dendritic cells associated with tumors, and render them more prone to effective recognition by the immune system, by inhibition of immune checkpoint inhibitors. The present disclosure further relates to methods for preparing such nanoparticles and to use thereof in the treatment of diseases, in particular cancer.

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).

An interferon (IFN)-anti-PD-L1 fusion protein, a pharmaceutical composition and a kit containing the same for treating tumors are disclosed. The fusion protein of the present invention can simultaneously target PD-L1 and IFN receptors, and the activation of IFN signals in a tumor microenvironment (TME) can enhance the PD-1 / PD-L1 therapy against tumors by inducing stronger T cell activation. The anti-PD-L1 antibody can be used to specifically deliver immunomodulatory molecules to tumor tissues, and the fusion protein results in the generation of multiple feedforward responses, which can increase the targeting effect, reduce the toxicity, and enhance the response to IFN therapy, thereby maximizing the anti-tumor effect.

Provided is a recombinant promoter system specifically inducing gene expression after T cell activation. Also provided is a new T cell activation-induced recombinant promoter constructed by modifying and optimizing GM-CSF, IFNg and IL2 promoters. When CAR-T cells are activated, the recombinant promoter can efficiently induce the expression of downstream genes, with the activity thereof being superior to that of a traditional NFAT-responsive promoter constructed based on a binding sequence of a nuclear factor of activated T cells. Further provided are a CAR-T cell comprising the T cell activation-induced recombinant promoter and the use thereof.

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.

Provided herein are novel antibodies to aPD-L1, aPD-L2, and aCD28. In some embodiments, the antibody is an aPD-L1 x aPD-L2 x aCD28 antibody. Such antibodies enhance anti-tumor activity by providing a co-stimulatory signal against T cell activation of tumor cells while also advantageously blocking inhibitory PD-L1: PD1 and / or PD-L2: PD1 pathway interactions.

The invention discloses a nano vaccine as well as a preparation method and application thereof. The nano vaccine provided by the invention is prepared by fusing a liposome of which the surface is coupled with an inhibitor of an inhibitory immune checkpoint and a cell membrane of a tumor antigen sensitized dendritic cell cultured by utilizing a tumor cell lysate and keyhole limpet hemocyanin. The obtained nano vaccine is uniform in particle size, the outer layer of the nano vaccine is wrapped by a cell membrane, and the nano vaccine has proper surface potential, size and structural flexibility and is beneficial to aggregation in tumors. After the nano vaccine reaches tumor tissues, antigens can be efficiently and directly presented to T lymphocytes through cell membranes of tumor antigen sensitized dendritic cells, a costimulatory signal necessary for T cell activation is fully provided, meanwhile, T cell depletion can be reversed through an immune checkpoint inhibitor, the function of the inhibited T cells is re-excited, and the T cells are activated. The cytotoxic function and the multiplication capacity of the T cells are effectively and specifically recovered through a double-line strategy.

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.