957 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 a bispecific cytokine fusion protein, which comprises an amino acid sequence of a type I cytokine and an amino acid sequence of a type II cytokine, and the amino acid sequence of the type I cytokine and the amino acid sequence of the type II cytokine are directly connected through a connecting peptide or are connected in series or in parallel through a fusion partner and the connecting peptide. Amino acid sequences of type I and type II cytokines are connected in series or in parallel to form the bispecific cytokine fusion protein, and the fusion protein can synergistically activate precursor depleted CD8 + T cells and terminal depleted CD8 + T cells, improve immunosuppression of a solid tumor complex microenvironment and release the potential of tumor immunotherapy. The invention further discloses nucleic acid, a carrier, a cell, a medicine or a medicine composition related to the bispecific cytokine fusion protein. The invention also discloses application of the bispecific cytokine fusion protein in preparation of drugs for treating cancers.

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 provides a nano photosensitizer modified by outer membrane vesicles of genetically engineered bacteria as well as a preparation method and application of the nano photosensitizer. The nano photosensitizer is a nano material with the particle size of 80-120 nm, and the nano photosensitizer modified by the genetically engineered bacterium outer membrane vesicle comprises dipalmitic acid phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), dioleoyl lecithin (DOPC), cholesterol, a small molecule dye and CD47nb-OMV membrane protein. The chemical structure of the small molecule dye is shown as a formula I or a formula II. The nano photosensitizer OBDlp modified by outer membrane vesicles of genetically engineered bacteria serves as a novel nano photosensitizer, tumor targeting PTT is mediated through NIR II FL / PA imaging, tumor immunogenicity is improved, antigen presenting cells are activated, and infiltration and functionalization of CD8 + T cells are caused. And OBDlp and laser are combined to induce release of a large amount of DAMPs and trigger ICD to promote maturation of cDC1s. Meanwhile, a CD47 nano antibody carried by the nano photosensitizer induces polarization of M1 phenotype macrophages by blocking a CD47-SIRP alpha signal transduction axis, and an immunosuppression tumor microenvironment is reversed.

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 relates to application of a GATA3 inhibitor and a PD1 inhibitor in preparation of a medicine for treating breast cancer, and belongs to the technical field of biological medicine. The invention discloses application of a GATA3 inhibitor and a PD1 inhibitor in preparation of a medicine for treating breast cancer. The GATA3 regulates the transcription regulation of IFNbeta by inhibiting the enhancer activity of IFNB1, down-regulates an I-type interferon signal channel, inhibits the secretion of an MHC-I antigen presentation channel and a chemotactic factor CCL5 of breast cancer cells, reduces immune recognition, and achieves the purpose of immune escape. The immunotherapy for inhibiting GATA3 combined with the PD1 inhibitor to treat breast cancer effectively treats breast cancer mice, improves the IFN beta level in the mice, promotes the MHC-I antigen presentation pathway of the mice, improves the CCL5 level in the mice, and improves the CD8 + T cell level in a tumor immune microenvironment, thereby reducing tumor occurrence and inhibiting tumor growth.

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 relates to the technical field of cancer treatment, and provides application of a lactyltransferase inhibitor in pancreatic cancer and immunotherapy thereof. According to the present invention, the histone lactosyltransferase inhibitor and the anti-programmed death receptor-1 antibody are combined to form the composition for pancreatic cancer and immunotherapy thereof, such that the recognition and the removal of the immune system on the cancer cells can be enhanced, the growth of the pancreatic cancer tumor can be effectively inhibited, and the survival time of the pancreatic cancer patient can be prolonged. The histone lactosyltransferase inhibitor reduces the infiltration level of tumor-associated neutrophil, increases the infiltration level of CD8 positive T cells, reverses the composition of a pancreatic cancer inhibitory immune microenvironment, and generates a synergistic anti-tumor effect with an anti-programmed death receptor-1 antibody. The traditional Chinese medicine composition is suitable for early-stage, middle-stage and late-stage treatment of pancreatic cancer, improves the survival rate and the treatment effect of pancreatic cancer patients, remarkably reduces the side effects of treatment and improves the living quality of the pancreatic cancer patients.

Transgenic rodents and rodent cells that express components of the human immune system, and their uses in generating human T cell receptors (TCRs). A genetically modified rodent comprising a TCR alpha gene locus comprising unrearranged human TCR alpha variable gene segments and a human TCR alpha constant region, and a TCR beta gene locus comprising unrearranged human TCR beta variable gene segments and a human TCR beta constant region. Use of hTCR transgenic rodents to generate antigen-specific CD8+ T cell responses for the discovery of fully human TCR sequences with therapeutic potential.

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.

The invention discloses a method for performing sarcoma high-frequency neoantigen function verification based on tumor organoids, and the method for performing sarcoma high-frequency neoantigen function verification based on tumor organoids comprises the following steps: after separating PBMC, enriching CD8 + T cells, and stimulating the CD8 + T cells by using DC loaded with candidate neoantigen polypeptide to obtain neoantigen specific CTL; new antigen-specific CTL is tested through the kit, secretion of IFN-gamma is detected, and antigen-specific CTL with positive reaction is screened out; the method comprises the following steps: selecting a candidate new antigen capable of specifically stimulating CTL to generate an IFN-gamma positive reaction according to an experiment result of secreting IFN-gamma by the CTL, establishing a tumor organoid-CTL cell co-culture system, setting PBMC primary T cells of a patient which are not stimulated by DC loaded with the candidate new antigen as a control group, and measuring organoid light microscope radiography and tumor cell death conditions. The function of the sarcoma high-frequency neoantigen is evaluated based on tumor organs.

The present invention provides binding agents that specifically bind to CD8+KIR+ T regulatory cells and their use in the treatment of diseases or disorders, such as an inflammatory disease, an autoimmune disease, cancer, or an infectious disease.

The invention discloses a method for in-vitro induction of T cell immune memory differentiation and application, CD8 + T memory differentiation can be enhanced by verifying in-vitro itaconic acid and derivative supplement thereof, and then anti-tumor and anti-infection immune response is enhanced after in-vivo feedback. The invention can be used in malignant tumors and infectious diseases to enhance the curative effect of T cell adoptive therapy.

Provided herein are methods and compositions for generating engineered cells, such as cells expressing a recombinant receptor, including methods involving stimulation and / or engineering of an input composition having a defined ratio of naïve-like CD4+ T cells to naïve-like CD8+ T cells. In particular, the methods can be used to engineer T cells with genetically engineered receptors, such as genetically engineered antigen receptors such as engineered (recombinant) TCRs and chimeric antigen receptors (CARs), or other recombinant chimeric receptors. Features of the methods include producing a more consistent and / or predictable T cell product and / or a product with lower toxicity compared with other methods.

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 relates to the field of biological medicine, in particular to application of fermented lactobacillus mucus in preparation of immune antitumor drugs. A strain of fermented lactobacillus mucus capable of effectively treating tumors is screened and can activate the immune system of the strain, increase the proportion of CD8 + T lymphocytes in spleen tissues, increase the infiltration proportion of leukocytes in tumors and the proportion of CD4 + and CD8 + T lymphocytes in infiltrated immune cells, change the tumor microenvironment and improve the tumor immunity. Therefore, tumor cells are effectively killed, and the effect of tumor immunotherapy is achieved.

The invention discloses a construction method of a model for predicting an esophageal squamous cell carcinoma intervention effect. The construction method comprises the following steps: acquiring detection data of a predictive factor in a sample; the predictive factors at least comprise the content or the expression level of a depletion marker of a functional CD8 T cell in a sample and the content or the expression level of a C1QC + macrophage immune checkpoint molecule; and predicting the intervention effect of the esophageal squamous cell carcinoma according to the detection data of the predictive factor. Establishing a space proteomics map of a complex space tissue of a tumor microenvironment (TME) during treatment; key spatial features which are related to specific cell behaviors and influence treatment results are determined and layered; a powerful prediction model of drug response is developed by utilizing a machine learning technology, and the area under curve (AUC) can reach 97%.

The present disclosure relates to T cells capable of co-expressing T cell receptors (“TCR”) together with CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods thereof.

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 present disclosure relates to modified immunocytokine compositions comprising antibodies or antigen binding fragments specific for immune cell antigens (e.g., PD-1) and IL-18 polypeptides which are able to selectively stimulate the immune system at desired locations, such as within a tumor microenvironment. Such immunocytokines are in some instances useful for the expansion of CD8+ T cells in a subject, preferably in a tumor or tumor microenvironment of the subject. Also provided herein are methods of treatment with and methods of manufacture of immunocytokine compositions.

The present invention inter alia relates to an enhanced chimeric CD8 Co-receptor, wherein the CD8 Co-receptor comprises a polypeptide including at least one functional polypeptide domain or a functional polypeptide motif of a CD8 Co-receptor, and wherein said polypeptide further comprises at least one CD8-derived polypeptide region including a functional polypeptide domain or a functional polypeptide motif of a wildtype human CD8 Co-receptor.The enhanced chimeric CD8 Co-receptor further comprises at least one cytoplasmic polypeptide domain or cytoplasmic polypeptide motif of a tumor necrosis factor receptor superfamily protein, a immunoglobulin superfamily (IgSF) protein, and / or an ITAM-associated receptor. The present invention also relates to a nucleic acid encoding the enhanced chimeric CD8 Co-receptor, a vector comprising the nuclear acid encoding for the enhanced chimeric human CD8 Co-receptor, as well as to isolated T-cells being transduced, transformed or transfected with the nucleic acid or the with the vector, and to isolated T-cells being transduced, transformed or transfected to express the enhanced chimeric CD8 Co-receptor as well as to engineered T-cells expressing the chimeric CD8 Co-receptor. The invention further relates to a kit for preparing the isolated T-cells of the present invention, as well as to a pharmaceutical composition comprising the T-cells. The invention also relates to a method for preparing a T-cell for immunotherapy, and to a method for treating a patient having a disease comprising administering the pharmaceutical composition.

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 discloses an immunoregulatory factor composition, which comprises a first component and a second component, the first component is a type I cytokine or a long-acting form thereof, and the second component is a type II cytokine or a long-acting form thereof; the long-acting form is formed by fusing a cell factor with a fusion partner through a connecting peptide or performing PEGylation modification on the cell factor, and the fusion partner is an Fc fragment of IgG or human serum albumin or an engineered mutant of one of the Fc fragment and the human serum albumin. The immunomodulatory factor composition synergistically activates precursor depleted CD8 + T cells and terminal depleted CD8 + T cells through a combination therapy of type I and type II cytokines. The invention also discloses nucleic acid, a carrier and a cell related to the immunomodulatory factor composition. The invention also discloses an application of the immunoregulatory factor composition in preparation of drugs for treating cancers. The immunoregulatory factor composition can relieve the depletion state of depleted T cells and improve the effector function and proliferation capacity of the depleted T cells so as to control tumor progression.