756 results about "CD8" patented technology

The present disclosure provides humanized antibodies and antigen binding domains thereof that bind CD8α and other antibody formats comprising these antigen binding domains, their use as a targeting moiety on lipid nanoparticles (tLNP) to deliver a therapeutic payload (such as a nucleic acid molecule) or other types of payloads. The present disclosure further relates to pharmaceutical compositions comprising the humanized anti-CD8α antibodies and CD8-targeted tLNP encapsulating a payload.

The invention relates to the technical field of biological medicine, and discloses a pharmaceutical composition of paclitaxel dimer prodrug nanoparticles and a traditional Chinese medicine compound and application of the pharmaceutical composition, and the pharmaceutical composition is composed of Qiyuansanlong prescription freeze-dried powder and paclitaxel dimer prodrug nanoparticles; wherein the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) or GSH (glutathione) response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs), and the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) and GSH response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs). According to the pharmaceutical composition disclosed by the invention, a traditional Chinese and western medicine synergistic treatment system is innovatively constructed, and the advantage of multi-dimensional synergistic interaction is shown. Firstly, an NQO1 / GSH double-response type intelligent release system is adopted, and a biomarker highly expressed by tumor tissue can be specifically responded to realize precise drug release, so that the PTX concentration in tumors is improved compared with that of a traditional dosage form, and meanwhile, the drug circulation time is prolonged. Secondly, the active ingredients in the Qiyuansanlong prescription freeze-dried powder can significantly down-regulate the PD-L1 expression level, synergistically enhance CD4 + T and CD8 + T cell infiltration, and form chemical-immune dual killing effects.

The invention discloses an application of CD4 + CD8 + double-positive T cells in improvement of poor immune reconstitution of HIV (human immunodeficiency virus) infected patients, and relates to the technical field of biological pharmacy, in particular to the application of preparation of the CD4 + CD8 + double-positive T cells in the poor immune reconstitution of the HIV infected patients. The number of peripheral blood CD4 + T cells of HIV infected patients is increased, the immune system of the patients is improved, and the probability of possible opportunity infection and other related diseases of the patients is reduced, so that the morbidity and mortality of the patients are reduced.

The method and system for evaluating the curative effect of hepatocellular carcinoma based on immune microenvironment characteristics are high in accuracy and reliability of evaluating the curative effect of hepatocellular carcinoma. The method comprises the following steps: (1) preparing a sample; (2) carrying out multiple immunohistochemical staining; (3) image acquisition and analysis; (4) analyzing spatial distribution characteristics; (5) multiplying the input image voxel signal numerical value by the weight vector of the convolution kernel, transmitting the multilayer convolution kernel, and finally obtaining a calculation result output by each network; and (6) establishing a prediction model: based on the spatial distribution characteristics and clinical characteristics of immune cells, constructing the prediction model by using the positive rate of CD8 + PD-L1 + and CD103 + CD8 + cells in the total area and the number of CD103 + cells within 30 microns around tumor cells so as to predict the immunotherapy curative effect of the HCC patient.

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

The invention discloses a method for constructing a differential diagnosis model for lupus nephritis and membranous nephropathy, and belongs to the technical field of intelligent medical treatment. The modeling method comprises the following steps: S1, respectively collecting flow cytometry detection data of lupus nephritis patients and healthy control personnel; s2, performing data cleaning and conversion on the flow cytometry detection data, and converting non-numerical features into digits; carrying out implication on the missing value by adopting a k nearest neighbor algorithm from an implication packet; s3, random sampling is carried out on the cleaned and converted data set, and samples are divided into a training set and a verification set according to the proportion of 7: 3; s4, dividing a training subset and a test set from the training set, and iteratively selecting the types of cells incorporated into the constructed model as pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T, and CD38 + PD-1 + CD8T by adopting an RFE method, wherein the types of the cells incorporated into the constructed model are pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T and CD38 + PD-1 + CD8T; and S5, performing a classification task by adopting TabPFNClassifier, performing training from features selected from the training data set, then evaluating the performance of the model, performing model training by utilizing detection data, and performing evaluation to construct a lupus nephritis prediction model with high accuracy.

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating triple negative breast cancer and application thereof. The traditional Chinese medicine composition is prepared from the following main active ingredients in parts by mass: 20 to 40 parts of radix astragali seu hedysari, 10 to 20 parts of rhizoma curcumae, 10 to 20 parts of herba hedyotidis diffusae, 5 to 15 parts of fructus aurantii immaturus, 5 to 15 parts of radix bupleuri, 5 to 15 parts of radix paeoniae alba and 5 to 15 parts of liquorice root. Animal experiments show that the traditional Chinese medicine composition can significantly inhibit tumor growth and pulmonary metastasis of triple-negative breast cancer tumor-bearing mice, increase the proportion of CD8 + T lymphocytes in blood, reduce the proportion of MDSCs, significantly down-regulate the expression of pro-inflammatory cytokines such as IL-6, IL-1alpha, CXCL1 and GM-CSF in serum, and cooperate with PD-L1 immunotherapy to achieve a synergistic effect. And the whole blood and liver and kidney function indexes are in a normal range. Therefore, the traditional Chinese medicine composition disclosed by the invention can be used for effectively inhibiting the tumor growth and pulmonary metastasis of the triple negative breast cancer, remodeling the immune state of an organism and reducing the release of proinflammatory factors, and is safe, reliable, free of obvious liver and kidney toxicity and blood toxicity and small in side effect.

The invention belongs to the technical field of biological medicines, and relates to application of Ackermann muciniphile or its external vesicles in preparation of a drug for treating schistosomiasis. The anti-infection immunity of a host is enhanced by adjusting intestinal flora balance (recovering diversity and composition) and improving immune response (adjusting macrophage, CD8 + T cell recruitment and Th1 / Th2 balance); meanwhile, the intestinal barrier function is improved, and pathogen invasion and inflammation are reduced; hepatic granuloma and hepatic fibrosis caused by schistosome infection are obviously relieved, and the liver function is improved; the key effect of the MIF gene in immunoregulation is disclosed, and a new direction is provided for schistosomiasis immunotherapy. Besides, the probiotics are high in treatment safety and free of obvious side effects, can be combined with chemotherapy to enhance the curative effect and reduce the side effects and drug resistance of chemical drugs, provides a lasting and comprehensive adjuvant therapy scheme for the schistosomiasis, and has important clinical application potential.

The invention relates to the technical field of nano-drug presentation systems, in particular to a TCR (T cell receptor) nano-vesicle antibody with both T cell redirection and immunosuppression reversal as well as a preparation method and application of the TCR nano-vesicle antibody. The TCR nano-vesicle antibody comprises a vesicle formed by a liposome and a cell membrane; tCR protein, a PD-1 antibody and a CD3 antibody are loaded on the vesicles. The nano vesicle antibody has the functions of T cell redirection and immunosuppression reversion; the difficulty of low stability of the soluble TCR is overcome; the polypeptide can be rapidly enriched in tumor tissues through tumor specificity TCR, and CD8 + T cells infiltrated by tumors are directly activated through an anti-CD3 antibody; depletion of T cells can be reversed through the PD-1 antibody on the surface, and the effector function of tumor infiltration CD8 + T cells is improved. The technical scheme can solve the technical problems that the TCR stability is not ideal and the immunosuppression state of the tumor microenvironment is difficult to overcome, and has ideal application and popularization prospects.

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a human or humanized T cell receptor (TCR) from a human or humanized TCR locus comprising a non-human TCR non-coding sequence, and optionally a humanized T cell co-receptor (e.g., humanized CD4 and / or CD8 (e.g., CD8α and / or CD8β)), and / or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and / or MHC II β chains) and / or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making the genetically engineered animals are also provided. Methods for using the genetically engineered animals for developing human therapeutics are also provided.

The invention discloses preparation and application of porcine reproductive and respiratory syndrome virus circular RNA (Ribonucleic Acid) and a vaccine. The circular RNA encodes and expresses GP5 protein optimized by the porcine reproductive and respiratory syndrome virus and M protein optimized by the porcine reproductive and respiratory syndrome virus. The optimized circular RNA molecule is prepared into a vaccine to successfully induce a high-level neutralizing antibody in a pig body, so that the proportion of CD4 + IFN-gamma + and CD8 + IFN-gamma + cells in PBMC cells is remarkably increased, the lymphocyte proliferation activity after specific stimulation of a virus antigen is remarkably improved, and the protection of the porcine reproductive and respiratory syndrome virus is effectively realized. The invention provides a basis for preparing the RNA vaccine for preventing and / or treating the porcine reproductive and respiratory syndrome virus.

The present disclosure provides humanized antibodies and antigen binding domains thereof that bind CD8α and other antibody formats comprising these antigen binding domains, their use as a targeting moiety on lipid nanoparticles (tLNP) to deliver a therapeutic payload (such as a nucleic acid molecule) or other types of payloads. The present disclosure further relates to pharmaceutical compositions comprising the humanized anti-CD8α antibodies and CD8-targeted tLNP encapsulating a payload.

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.

In various embodiments immunogenic nanoparticles are provided that are capable of raising an immune response directed against SARS-CoV-2. In certain embodiments the immunogenic nanoparticles comprise mRNA multi-epitope vaccines that can be used in combination with or independent of other covid-19 vaccines (e.g., the spike protein mRNA vaccine(s)) to invoke a strong CD8+ or CD4+ T-cell as well as neutralizing antibody producing B-cell responses. In certain embodiments this vaccine is based on the rational combination of well-conserved T- and B-cell epitopes identified COVID-19 and viral variants.

The invention relates to an mRNA (messenger Ribonucleic Acid) vaccine targeting FomA and application of the mRNA vaccine in immunotherapy of esophageal squamous carcinoma in the technical field of tumor immunotherapy. The problems that in the prior art, a specific targeting vaccine for the fusobacterium nucleatum membrane protein FomA lacks, traditional antibiotics can only kill extracellular bacteria and cannot remove intracellular colonized fusobacterium nucleatum, and cellular immunity cannot be effectively activated to remove fusobacterium nucleatum colonized in tumor tissue; the immunotherapy drug resistance of esophageal squamous carcinoma caused by fusobacterium nucleatum infection is difficult to reverse. According to the technical scheme, an mRNA molecule with a fusobacterium nucleatum FomA extracellular domain tandem repeat sequence and a lipid nanoparticle delivery system are coded, an extramembrane segment tandem repeat immune enhancement technology is adopted for design, two extracellular ring sequences are repeated for 2-5 times and connected through a connector sequence, lipid nanoparticles are composed of optimized quaternary lipids, and the lipid nanoparticles are prepared from the quaternary lipids. And a PD-1 monoclonal antibody is combined to activate FomA specific CD8 + T cell immunoreaction, so that comprehensive removal of intracellular and extracellular bacteria and bacteria targeted immune remodeling are realized.

The invention belongs to the technical field of cellular immunity, and particularly relates to calcium-doped manganese phosphate engineered red blood cells based on a biomimetic mineralization technology and application of the calcium-doped manganese phosphate engineered red blood cells in immunotherapy. Calcium ions, manganese phosphate, acidic polypeptide and a carboxyl activator are deposited on the surfaces of red blood cells, the acidic polypeptide provides a negative electricity environment, the concentration of calcium and manganese on red blood cell membranes is increased, and a mineralization layer of calcium ions and manganese ions is formed; the carboxyl activator can activate carboxyl of amino acid on acidic polypeptide and is covalently bound with other molecules; calcium can improve the stability of the manganese phosphate crystal, optimize the release of manganese ions and activate a cGAS-STING pathway in the DC; the natural half-life period of red blood cells reaches 120 days, rapid clearing of the liver can be avoided, the aged red blood cells are swallowed by spleen DC, and cross presentation of antigens is promoted. The calcium-doped manganese phosphate engineered erythrocyte provided by the invention can promote the maturation, migration, homing and antigen presentation functions of dendritic cells, and enhance the ability of the dendritic cells to activate CD8 + T cells.

Disclosed are methods for reducing T cell exhaustion and / or treating male sex biased cancers through the administration of agents that inhibit androgen receptor. In some aspects the methods further comprise the detection of a male sex biased cancer and / or T cell exhaustion via detection of TOX+ and / or T cell factor 1 (TCF1)+ T cells in the tumor microenvironment.

The invention discloses application of CD146 + umbilical cord mesenchymal stem cell subpopulation in preparation of drugs for preventing and treating immune thrombocytopenia and a product, and relates to the technical field of biology. The invention provides an application of a CD146 + mesenchymal stem cell subset in preparation of a medicine for treating or preventing immune thrombocytopenia. The CD146 < + > mesenchymal stem cell subpopulation can increase the number of platelets of ITP patients, regulate the CD4 < + > / CD8 < + > ratio of the ITP patients and remarkably reduce the MDSC proportion, so that the in-vivo immune state is changed.

Described herein are serum-free and feeder-free methods and compositions for the tunable differentiation and production of CD4+ (single positive) T cells and CD8+ (single positive) T cells, by adjusting T cell receptor (TCR) stimulation and notch activation (or notch signaling activation, stimulation or inducement). In some other aspects the invention provides a method and in vitro niche and cell culture media that results in enhancing CD4+ (SP) T cell generation, including naive mature CD4+ single positive T cells from double positive (DP) CD4+8+cells or CD8+(SP) T cells by TCR stimulation while having low or no notch signaling activation, stimulation or inducement. In yet other aspects, the invention provides a method, niche and culture media for producing cells derived from CD4+ (SP) T cells, including Treg cells.

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 disclosure provides a cytokine engager comprising an antibody that specifically bind human CD8, and wherein the antibody is fused to a cytokine (e.g., IL-2). Compositions and Methods of administering the compositions to preferentially expand T cells and treat cancer are also provided.

The invention discloses a lupus nephritis marker and application thereof, and belongs to the technical field of biomarkers. The marker for the lupus nephritis, disclosed by the invention, comprises one or more of CD8, CD38 and PD-1. By detecting specific cell surface markers in patient blood, early diagnosis of LN is assisted in a minimally invasive mode, and based on deep comparative analysis of LN patients and healthy people, the specificity and sensitivity of the biomarkers in LN diagnosis are ensured through screening of the biomarkers. In the aspect of differential diagnosis, a clinician is assisted to distinguish LN from other types of kidney diseases, such as membranous nephropathy (MN) and anti-neutrophil cytoplasm antibody related vasculitis (AAV), by analyzing specific biomarker modes of different nephropathy. The dependence on kidney puncture is reduced, related potential risks and inconvenience are avoided, and meanwhile more accurate and timely diagnosis is provided for an SLE patient.

The invention relates to the field of tumor immunotherapy, in particular to an mRNA vaccine targeting fusobacterium nucleatum membrane protein FomA and application of the mRNA vaccine in esophageal squamous cell carcinoma immunotherapy. The vaccine comprises a nucleotide sequence for coding a specific epitope of FomA, and the specific epitope contains 1-10'GGSGGGGSGG 'repetitive sequences and has homology gt in different strains; 95%. The mRNA is encapsulated in lipid nanoparticles (the particle size is 80-150 nm, the polydispersity coefficient is lt; and the liposome is composed of 38-42% of cationic lipid, 18-22% of neutral lipid, 33-37% of cholesterol and 3-5% of PEG modified lipid, and the encapsulation efficiency is 85-95%. The vaccine can specifically reduce the abundance of fusobacterium in tumors by 72.4 + / -8.0%, the tumor microenvironment is converted into an immune activation type, and the proportion of CD8 + T cells is increased from 5.2 + / -1.0% to 14.5 + / -2.0%. When the compound is combined with a PD-1 inhibitor, the objective remission rate reaches 70%, the tumor volume is reduced by 78.5 + / -8.0%, and the compound is suitable for treating clostridium-enriched esophageal squamous carcinoma.

The invention relates to a traditional Chinese medicine compound composition for inhibiting lung cancer metastasis and application thereof. The traditional Chinese medicine compound composition is prepared from the following raw material medicines in parts by weight: 40-45 parts of radix ophiopogonis, 4-8 parts of pinellia ternate, 4-8 parts of liquorice, 7-11 parts of ginseng, 4-8 parts of polished round-grained rice, 12-20 parts of Chinese dates and 18-27 parts of paris polyphylla. Compared with the prior art, the traditional Chinese medicine composition has a remarkable inhibiting effect on lung cancer metastasis, can remarkably induce lung cancer cell apoptosis and effectively inhibits proliferation and migration of lung cancer cells; animal experiments show that the traditional Chinese medicine composition not only can effectively reduce the number of mouse lung metastatic tumors, but also remarkably reduces the lung tumor metastasis load. In addition, the traditional Chinese medicine composition also remarkably increases the level of NK cells and CD8 + T cells in peripheral blood.

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 spleen-targeted nano platform construction method suitable for tumor vaccination, and particularly relates to the field of vaccines.The spleen-targeted nano platform construction method comprises the steps that S1, CL15H6-DOPS LNPs, spherical polymer vesicles and erythrocyte membrane coated nano-particles are selected as spleen-targeted nano-carriers; s2, integrating an immunologic adjuvant; mn < 2 + > doped LNPs, ultrasonic response lipidosome and a CD3 antibody are selected to be coupled to serve as an integration material; s3, delivering in vivo; animal models are selected for in-vivo delivery and curative effect verification, and B16F10 melanoma mice, MC38 colon cancer mice and non-human primates are selected as the animal models respectively. By optimizing the chain length and the surface topological structure (such as spherical polymer vesicles) of the liposome, the spleen enrichment rate is remarkably increased, and the red marrow myeloid cell uptake efficiency is enhanced. By combining with common delivery of a manganese adjuvant, an STING channel is activated, secretion of type I interferon is promoted, and the proportion of antigen-specific CD8 + T cells and the tumor inhibition rate are increased.

The invention discloses application of T cell subgroups in preparation of a kit for evaluating B cell depletion therapy and application of the T cell subgroups in preparation of the kit for evaluating B cell depletion therapy, the T cell subgroups comprise one or more of CD4 + TCM, CD4 + TEM, CD8 + TCM, CD8 + TEM, CD20 dimCD4 + TCM, CD20 dimCD4 + TCM, CD20 dimCD8 + TEM, Th17.1, Th17, Th2, CD4 + TCMTh17.1, CD4 + TEMTh17 and CD4 + TEMTh2, and the T cell subgroups comprise one or more of CD4 + TCMTh17, CD4 + TEMTh17 and CD4 + TEMTh2.

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.