341 results about "CD8" patented technology

The invention belongs to the technical field of biological medicine, and provides CKS1B serving as an immunotherapy response prediction biomarker and application of the CKS1B, and according to the application, CKS1B serves as an immunotherapy response marker, and a CKS1B inhibitor is combined with an active component to treat a model mouse. In-vitro cell experiments are adopted to evaluate the immunotherapy prediction effect of the CKS1B as a biomarker on esophageal squamous carcinoma, a Cks1b overexpression tumor mouse model, a homologous mouse model and a human immune reconstruction mouse model are established, and a CKS1B inhibitor is combined with active ingredients to treat the two models; results show that the CKS1B inhibitor combined with the active component can promote removal of esophageal squamous carcinoma cells by CD8 + T cells, inhibit interferon signal channels and antigen presentation, effectively recover immune response, inhibit tumor cell proliferation and significantly reduce tumor volume, so as to achieve the purpose of treating esophageal squamous carcinoma.

Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen / LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

The invention discloses an aptamer-modified lipid nano delivery platform as well as a preparation method and application thereof, and belongs to the field of biomedicine. The platform is prepared by taking DPPC, DOTAP and cholesterol as basic lipid components, Ce6 as a sound-sensitive agent and Flt3L as an immune agonist, controlling the particle size through gradient extrusion, and coupling cholesterol with an EpCAM aptamer for surface modification. The method has the core advantages that active targeting enrichment of tumors is realized by virtue of the aptamer, tumor cell immunogen cell death (ICD) is induced in combination with a sonodynamic therapy (SDT), and damage-related molecular patterns (DAMPs) are released; meanwhile, Flt3L is released in a tumor microenvironment, collection and activation of type 1 classical dendritic cells (cDC1) are specifically promoted, an'endogenous cDC1 vaccine 'is constructed, and CD8 + T cell mediated anti-tumor immune response is enhanced. Experiments prove that the platform can significantly improve the cDC1 infiltration level of a tumor site, effectively inhibit the progress of prostate cancer (PCa), and provide a new normal form for immune'cold tumor 'treatment.

The invention discloses a regulation mechanism research method of depleted precursor CD8T cells, and relates to the field of immunology and molecular biology. Comprising the following steps: detecting the expression level of the ARHGAP9 gene in a chronic virus infection model; constructing a T cell specific ARHGAP9 gene knockout animal model; the influence of ARHGAP9 deletion on the frequency, phenotype and function of the Tpex cell is analyzed; a single cell transcriptome sequencing technology reveals that ARHGAP9 regulates and controls a downstream signal channel of a Tpex cell. By constructing a chronic virus infection model, detecting the expression dynamic state of the ARHGAP9 gene, knocking out an animal model by utilizing T cell specificity ARHGAP9, and combining flow cytometry, qPCR, single cell transcriptome sequencing and other technologies, the invention discloses the effect of the ARHGAP9 as a novel immune checkpoint molecule, and provides a theoretical basis for developing Tpex cell targeting immunotherapy.

The invention discloses a method and a device for detecting CAR (Chimeric Antigen Receptor) cells. The method comprises the following steps: taking a genome of a sample to be detected as a template, carrying out fluorescent quantitative PCR reaction by using a primer and a probe aiming at the sequence of a CD8 alpha transmembrane region-41 BB costimulatory molecule in a CAR gene to obtain a CT value, and calculating the copy number of the CAR gene according to the CT value and a standard curve to obtain the CAR cell distribution. Specific primers and probes are designed for CAR cells containing CD8 alpha transmembrane region-41BB costimulatory molecules, a fluorescent quantitative PCR method for detecting the copy number of CAR genes is developed, then the CAR cells are quantified, and it is proved that the method has wide applicability through multi-angle verification analysis and limitation of detection standards.

The invention discloses application of a palmitoylation inhibitor in prevention and treatment of gastric cancer. The chromatin remodeling protein SNF2 derived from S.anginosus EVs can be combined with a transcription factor TEAD1, so that the transcription of the palmitoyl transferase ZDHHC11 is promoted together. Then, the stability of the ZDHHC11 is enhanced by catalyzing palmitoylation of PD-L1, and finally immune escape is induced. In addition, SNF2 also can activate AXL, CTGF, CYR61 and other carcinogenic targets at the downstream of TEAD1, thereby further accelerating the malignant progression of gastric cancer. In an in-vivo experiment, the intragastric administration of the S.anginosus EVs not only promotes the tumor growth of mice, but also significantly inhibits the infiltration of CD8 + T cells. Blocking of ZDHHC11 can effectively reverse immune escape, and has a synergistic effect with an anti-PD-1 therapy, so that the treatment effect is remarkably improved.

The invention belongs to the technical field of biological medicine, and particularly relates to a nano vaccine based on GD2 mimetic peptide as well as a preparation method and application of the nano vaccine. The nano vaccine provided by the invention comprises a GD2 mimetic peptide, an STING agonist and a polymer carrier, wherein the STING agonist is used as an immunologic adjuvant. The antigen peptide (GD2 mimic peptide 47-LDA) and the adjuvant (STING agonist) are wrapped in the micelle to prepare the nano vaccine GD2-NV, so that the druggability of the antigen peptide and the STING agonist is improved, and the accumulation of drug tumors and drainage lymph node parts is improved. Besides, the nano vaccine can respond to a lysosome acid environment, realize lysosome escape, enhance antigen cross presentation of DC, activate an STING pathway, improve infiltration and activation degrees of CD8 + T cells, induce lasting humoral immune response and inhibit growth and recurrence of tumors, and is good in biological safety.

The invention provides an application of combination of SPRC and a PD-1 or PD-L1 inhibitor in preparation of a lung cancer immunotherapy sensitizing drug, and relates to the technical field of biomedicine.In the application, through in-vitro cell experiments, cell co-culture experiments and in-vivo animal experiments, S-propargyl-L-cysteine (SPRC) can play a sensitizing role in the anti-lung cancer curative effect of the PD-1 inhibitor, and can be used for preparing a sensitizing drug for lung cancer immunotherapy. The core mechanism is as follows: 30 [mu] M SPRC is in a non-cytotoxic dose window and can specifically inhibit IFN-gamma induced STAT1 phosphorylation and PD-L1 up-regulation by depending on a CSE / H2S pathway, while IFN-gamma-STAT1-PD-L1 is a core signal axis of PD-L1 adaptive up-regulation in lung cancer cells, and the induction effect of TNF-alpha on PD-L1 is relatively weak; meanwhile, SPRC can inhibit activation of NF-kB induced by TNF-alpha and expression of inflammatory factors such as IL-6 and IL-8 through the pathway so as to exert the anti-inflammatory effect, the CD8 + T cell depletion proportion can be remarkably reduced by combining SPRC with anti-PD-1, the synergistic tumor inhibition effect is formed, the effect is verified in in-vivo and in-vitro experiments, and a closed loop of an in-vitro mechanism and an in-vivo curative effect is achieved.

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 invention provides a vaccine composition comprising an influenza virus peptide comprising a CD8+ T cell epitope and an influenza virus peptide comprising a B cell epitope, wherein each peptide is attached to a nanoparticle.

The application discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

The application discloses a recombinant oncolytic virus targeting CD317 gene and application thereof in anti-tumor, and belongs to the technical field of tumor treatment. The recombinant oncolytic virus comprises a CD317 inhibitor and an oncolytic virus, and is formed by integrating the CD317 inhibitor into the oncolytic virus genome. The CD317 inhibitor is a substance capable of inhibiting CD317 gene expression or targeting degradation of CD317 protein function, and is selected from shRNA or siRNA targeting CD317. The application develops the oncolytic virus targeting knockdown of CD317 expression, inhibits tumor cell proliferation by reducing CD317 expression of tumor cells, reduces PD-L1 expression so as to break the immune escape mechanism, simultaneously enhances the killing sensitivity of tumor cells to CD8+ T cells, forms a synergistic effect with the oncolysis of the oncolytic virus, and the recombinant oncolytic virus has stronger in-vivo anti-tumor activity, thereby providing a new potential scheme for CD317-driven tumor treatment.

A vaccine for use in the prophylaxis and / or treatment of a diseaseThe present invention relates to an adenoviral vector capable of encoding a virus-like particle (VLP), said VLP displaying an inactive immune-suppressive domain (ISD). The vaccine of the invention shows an improved immune response from either of both of the response pathways initiated by CD4 T cells or CD8 T cells.

The invention discloses a method and a system for analyzing immune cell change of an HER2 variant lung cancer patient. The method comprises the following steps: collecting a peripheral blood sample and carrying out single-cell RNA (Ribonucleic Acid) sequencing; performing quality control, standardization processing, dimensionality reduction and clustering analysis on the sequencing data; carrying out immune cell subset annotation on the clustering result based on a preset immune cell marker; analyzing cell communication modes among different immune cell subpopulations by using a ligand-receptor database; performing quantitative statistics on the proportion of various immune cells based on sample grouping; and further performing subpopulation fine analysis, quasi-time sequence trajectory reconstruction and metabolic pathway activity evaluation on the CD8 + T cells to construct a comprehensive immune cell map. According to the method, the multi-dimensional characteristics of the peripheral blood immune cells can be presented at high resolution, and the comprehensive analysis of the functional state, the communication network and the metabolic activity of the immune cells is realized. According to the system and the device, automatic operation and visual display of the method can be realized. According to the invention, the immune monitoring efficiency can be improved, and an effective tool is provided for immune treatment effect evaluation and disease mechanism research.

The invention discloses an elephant source bacillus licheniformis and application thereof. The preservation number of the bacillus licheniformis strain L517 is GDMCC 67825, the bacillus licheniformis strain L517 is classified and named as bacillus licheniformis, and the preservation date is February 26, 2026. Research finds that the bacillus licheniformis has a remarkable treatment effect on acute colitis of mice; and the traditional Chinese medicine composition also has a remarkable treatment effect on mouse subcutaneous colon cancer. The anti-cancer mechanism is that the infiltration of GZMB < + > CD8 < + > cytotoxic T cells in a tumor microenvironment is remarkably promoted in vivo through a supernatant metabolite of a culture medium, and a tumor suppressor gene P53 can be directly up-regulated. It is found for the first time that the elephant intestinal tract source bacillus licheniformis with evolutionary disease-resistant advantages shows good anti-proctitis and colon cancer activity, and can become an effective medicine for treating proctitis and colon cancer in the future.

We have discovered that allogeneic HSC-engineered human iNKT (3rdHSC-iNKT) cells display potent anti-GvHD functions, by eliminating antigen-presenting myeloid cells in vitro and in xenograft models, without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia. The 3rdHSC-iNKT cells closely resembled the CD4−CD8− / + subsets of endogenous human iNKT cells in phenotype and functionality. Embodiments of the invention harness these discoveries in new methods and materials for alleviating graft versus host disease.

A cancer immunotherapy for treating cancers such as melanoma is presented. A method for treating cancer in a subject via administration of anti-LY6E antibody to the subject. The method can further include administering an IFNAR blockade to inhibit type-1 interferon (IFN) signaling, thereby enhancing the ant-tumoral cytotoxic activity of T cells. The IFNAR can include anti-IFNα. The method can also include administering anti-PD1 antibody prior to, commensurate, or after treatment with anti-LY6E. A composition for treating cancer and modulating immune responses in a subject is also included. The composition can include, among other things, the anti-LY6E antibody, the IFNAR blockade, and anti-PD1. The composition and method also present a mechanism to modulate immune response in a subject by preventing upregulation of a Ly6ahigh T-cell subpopulation in response to a stimulus such as cancer, UVB, or interferons.

The invention discloses application of a nerve injury induction protein 1 in preparation of a gastric cancer diagnosis and treatment product. The invention finds that the overexpression of NINJ1 not only can enhance the sensitivity of gastric cancer cells to ferroptosis by down-regulating the expression of aldehyde ketoreductase AKR1C1 / 2 / 3, but also can up-regulate the expression of MHC-I molecules on the surfaces of tumor cells, promote the presentation of tumor antigens and increase the infiltration of CD8 + T cells, so that the dual anti-tumor function is exerted; therefore, NINJ1 overexpression and an immune checkpoint inhibitor (such as a PD-L1 antibody) or a ferroptosis inducer are combined for use, so that the immunotherapy effect can be synergistically improved. The invention provides a brand new targeting strategy for overcoming the immune drug resistance of gastric cancer and improving the treatment effect, and has important clinical transformation value.

The application discloses a kind of biomarkers for evaluating systemic lupus erythematosus to lupus nephritis progression, prediction model and application, belong to lupus nephritis prediction technical field.The application provides a kind of for evaluating systemic lupus erythematosus to lupus nephritis progression prediction model, the prediction model is according to the ratio of biomarker CD8 / CD4 and the κ / λ ratio of naive B cell, carries out binary Logistic regression analysis, obtains LogitP value, by comparing the high and low of the LogitP value and critical value 0.66938, predicts systemic lupus erythematosus to lupus nephritis progression situation.The prediction model constructed in the application aims to identify the individuals in lupus patients who may develop into lupus nephritis.This innovative model not only provides important guidance in the diagnosis, prognosis prediction and efficacy evaluation of the disease, but also provides a new perspective for the clinical management of lupus nephritis.

Provided is a use of mitofusin 2 (MFN2), an MFN2 variant capable of interacting with SERCA2, or an MFN2 expression promoter in maintaining and / or promoting tumor-killing capability and / or viability of a CD8 T cell. Also provided is a use of a CD8 T cell overexpressing MFN2 or a variant thereof for treatment of cancer.

The invention discloses an application of indole-3-pyruvic acid in preparation of an NF-kappa B signal channel activator. The research on the influence of the indole-3-pyruvic acid on NF-kappa B signal channels in breast cancer cells and killer T cells (CD8 + T cells, Tc) proves that the indole-3-pyruvic acid can activate the NF-kappa B signal channels in the breast cancer cells and the CD8 + T cells, so that the indole-3-pyruvic acid can be used for preparing the medicine for improving the tumor immunosuppressive microenvironment.

The application belongs to the technical field of tumor immunotherapy, and particularly relates to a composition for enhancing tumor immunogenicity and application thereof. The composition for enhancing tumor immunogenicity comprises, in terms of mass fraction, 10-15 parts of radix stephaniae tetrandrae, 10-20 parts of radix astragali, 3-9 parts of glycyrrhiza uralensis, and 3-12 parts of atractylodes macrocephala. The composition for enhancing tumor immunogenicity provided by the application is a natural traditional Chinese medicine prescription, has good biocompatibility, low toxicity and side effects, and is suitable for long-term treatment. The composition enhances immunogenicity by up-regulating MHC-I expression of tumor cells, activates CD8 + T cell-mediated anti-tumor effect, realizes autologous immunotherapy, and can avoid related side effects of exogenous immunotherapy. The composition can also be used in combination with a PD-1 blocker to synergistically improve anti-tumor efficacy and prolong patient survival.

The application provides a polypeptide vaccine delivery carrier, which is a phenylalanine-based polyester amide polymer prepared from triethylamine, p-nitrophenol, L-phenylalanine and butanediol. + The polypeptide vaccine has good stability, high antigen presentation effect, and can induce the body to produce effective antitumor CD8 T cell immune response, inhibit tumor growth and metastasis, and improve the effect of immunotherapy.

The invention discloses a method for predicting the curative effect of triple negative breast cancer immunotherapy by spatially quantizing CD39 + CD103 + CD8 + T cells, and relates to the technical field of biology.The method comprises the following specific steps that S1, an FFPE tumor tissue sample of a TNBC subject before immunotherapy is obtained, and a continuous section with the thickness of 3-5 microns is prepared and attached to a positive charge glass slide; s2, staining the section by using a combination containing CD8 / CD103 / CD39 / Pan-CK antibodies through a TSA sequential staining method, and then re-staining cell nucleuses by using DAPI; according to the method, spatial quantitative analysis is performed on a specific CD39 + CD103 + CD8 + T cell subset, a percentage index of target cells in CD8 + T cells and an average distance index of the target cells and nearest Pan-CK positive cells in a cancer nest region are set, and the target cells are determined according to comparison between the two indexes and a preset threshold value. According to the method, whether a subject is a potential benefit crowd treated by an anti-PD-1 / PD-L1 immune checkpoint inhibitor or not is accurately judged, a standardized technical means is provided for clinically screening the potential benefit crowd for immunotherapy, the accuracy and effectiveness of triple-negative breast cancer immunotherapy are effectively improved, and invalid treatment is reduced.

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.

The present application relates to a method for preparing and expanding a TSCM cell in vitro. Specifically, the method comprises: 1) obtaining an isolated CD8+ T cell; 2) activating the CD8+ T cell; 3) mixing the activated CD8+ T cell, a fibrinogen solution and a thrombin solution, and culturing same under conditions suitable for cell growth, so as to obtain a TSCM cell culture; and 4) bringing the culture into contact with a dispase so as to obtain a TSCM cell. The present application also relates to a kit for preparing and expanding a TSCM cell in vitro, the use of fibrinogen and thrombin in the preparation of a kit for preparing and expanding a TSCM cell in vitro, and a TSCM cell obtained by means of the method or kit of the present application.

Compositions and methods of glycosylated virus-like particles (VLPs) displaying user-defined antigens and optionally encapsidating TLR ligands for targeting dendritic cell lectins have been developed. The VLPs employ ligands for a DC lectin e.g., DC-SIGN to activate dendritic cells (DC) and drive proliferation of antigen-specific CD8 and CD4-T cells specific for a user-defined antigen, such as a tumor antigens. In some forms, the compositions include aryl-mannose ligands to effectively generate DC-mediated TH-1 T cell responses to the user-defined antigen.

Provided are a T cell culture medium, a cell culture, a culture method therefor, and an application. The culture medium comprises IL7 and TGFβ. A method for obtaining T cells comprises contacting immune cells with a culture medium, and resulting CD4 / CD8 positive mixed T cells and universal T cell cultures have high cell proliferation capacity, viability and in vivo efficacy after cryopreservation and thawing.