48 results about "Immune recognition" patented technology

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 discloses a universal HLA antigen presentation prediction method based on a protein language model and a multi-modal neural network, which comprises the following steps: firstly, extracting verified HLA binding peptide fragment sequences from an immune epitope database, generating equivalent non-epitope peptide fragment sequences in combination with a protein database, and constructing an HLA-I class and HLA-II class balanced data set; then, extracting sequence embedding characteristics and contact graph structure information of the peptide fragment sequence by utilizing a protein language model; the method comprises the following steps: processing a protein map constructed by a contact map through a map neural network to obtain global structure features, and meanwhile, carrying out regional convolution and residual convolution processing on sequence embedding by adopting a one-dimensional convolutional neural network (1DCNN) to extract local context sequence features; the method effectively fuses sequence semantics and space structure information, improves the accuracy and generalization ability of HLA antigen presentation prediction, and is suitable for immune recognition modeling tasks under various HLA subtypes.

The invention discloses an industrial control network risk monitoring method based on immune recognition, and relates to the technical field of network security risk monitoring, and the method comprises the steps: obtaining multi-source heterogeneous industrial control protocol flow data and a known data set which are collected in real time; preprocessing the data to obtain a standardized antigen vector; according to the standardized antigen vector, carrying out mixed training on a preset depth auto-encoder and a graph neural network model based on an immune algorithm to obtain a trained depth auto-encoder-graph neural network model and an initial detector population; inputting the standardized antigen vector into a lightweight model to obtain a compressed antigen vector; and detecting the compressed antigen vector based on the initial detector population to obtain an antigen vector for triggering an alarm. According to the method, the definition and expandability of original protocol semantics are improved, continuous coverage of unknown attacks is ensured, and the deployment and updating process of the model is optimized.

The invention discloses a purification method for removing endotoxin in prokaryotic expression recombinant protein, which belongs to the technical field of bioengineering, and comprises the following steps: adding 0.1% Triton X-114 in an ultrasonication stage, carrying out ice-bath ultrasonication, after the recombinant protein is combined with a Ni-NTA affinity column, washing with 50 column volumes of a combination buffer solution containing 0.1% Triton X-114, and carrying out elution by using an elution buffer solution containing 0.1% Triton X-114 in the presence of an elution buffer solution containing 0.1% Triton X-114 in the presence of an elution buffer solution containing 0.1% Triton X-114 in the presence of an elution buffer solution containing 0.1% Triton X-114; and washing with a 4-DEG C binding buffer solution with 20 column volumes, and subsequently eluting the target protein with imidazole with different gradients. Then, regulating the pH value of the purified recombinant protein solution to 2-4 or more than 10 through 100mM hydrochloric acid or sodium hydroxide, dissociating and decomposing endotoxin, carrying out oscillation treatment at room temperature for 2-4 hours, then removing the endotoxin in the recombinant protein through ultrafiltration, retaining an endotube protein solution, and detecting the content of protein and the endotoxin in the recombinant protein; the method is easy and convenient to operate and low in cost, the endotoxin content in the recombinant protein prepared through prokaryotic expression can be reduced by 400 times on the premise that immune recognition of the recombinant protein and serum is not affected, and the phenomenon that strong cross reaction occurs between immune serum and escherichia coli due to high endotoxin residues in the recombinant protein is reduced.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and uses thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The application discloses a kind of rice mycotic acid hapten and antigen preparation application, it is related to antigen preparation technical field, introduce sulfydryl in the 2 of rice mycotic acid, and obtain rice mycotic acid antigen by coupling with protein through connecting arm, rice mycotic acid hapten and antigen preparation application include the following specific flow: S1, the synthesis of rice mycotic acid hapten;S2, the preparation of rice mycotic acid immunogen;S3, the preparation of rice mycotic acid coating original;S4, the preparation of rice mycotic acid monoclonal antibody;S5, the preparation of rice mycotic acid immunofluorescence detection card;S6, rice mycotic acid detection in food;S7, detection limit experiment;S8, false positive rate, false negative rate experiment.The rice mycotic acid hapten retains the structural characteristics of rice mycotic acid, better exposes rice mycotic acid structural characteristics, improves the immunity and immune recognition ability of antigen, lays foundation for preparing specific, high sensitivity antibody, and improves its rapid detection ability.

The invention discloses a doxorubicin polymer prodrug loading method, which adopts linear or T-shaped structure polyethylene glycol as a polymer carrier, when the polymer carrier is the linear structure polyethylene glycol, the volume ratio of the polymer carrier to doxorubicin is (1-5): 1, and the volume concentration of the doxorubicin is 2-10%; when the polymer carrier is polyethylene glycol with a T-shaped structure, the volume ratio of the polymer carrier to the adriamycin is 1: 1, and the volume concentration of the adriamycin is 2-10%. Compared with the prior art, the doxorubicin can be efficiently wrapped, the targeting and controllability of drug release are improved, the immune recognition and rejection of an organism to a drug carrier are reduced, and the safety and tolerance of the drug are improved.

Provided herein are CD70-targeted chimeric antigen receptors (CARs), genetically engineered cells such as T cells containing the same, and related methods and uses of the genetically engineered cells in allogeneic cell therapy. Also provided are T cells that are genetically engineered with a CAR, such as a CD70-targeted CAR, and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

The invention discloses a flow type single molecule detection probe and method based on rolling circle amplification and application in the technical field of biomolecule detection. The flow type single molecule detection probe comprises a plurality of groups of magnetic bead detection probes and antibody binding probes which are used in pairs, each magnetic bead detection probe comprises a superparamagnetic microsphere, and the surface of the superparamagnetic microsphere is covalently connected with a plurality of fixed antibody probes; each fixed antibody probe comprises a first antibody and a first fixed DNA chain; each antibody binding probe comprises a second antibody and a second fixed DNA chain; aiming at the same target antigen, the first antibody and the second antibody in the same group can be specifically combined with different epitopes of the target antigen to form a sandwich immune complex. According to the invention, the hairpin structure DNA probe is combined with the adjacent ligation and rolling circle amplification technology to form dual specific screening of immune recognition and DNA ligation, so that the signal-to-noise ratio and sensitivity of detection are remarkably improved, and the design complexity, development cost and cross reaction risk of a multi-target detection system are greatly reduced.

The invention discloses a non-physical isolation digital ELISA detection method based on a fluorescent microsphere probe, a kit and application, and belongs to the technical field of biomedical detection. The method depends on a high-brightness fluorescent microsphere probe, realizes single-molecule immune recognition visualization and fluorescent particle digital counting under the condition of no physical isolation structure, simplifies system configuration based on an open type flat immune chip, improves the performance of a detection platform, overcomes the limitation of physical isolation type digital ELISA, is highly compatible with common equipment, and is suitable for large-scale popularization and application. The adaptation and popularization cost is reduced, and the portability and adaptability are good. High-brightness silicon-based fluorescent microspheres doped with fluorescent nanoparticles are adopted, so that high-sensitivity detection is realized; and establishing a database by using a standard product to realize absolute quantitative analysis. The kit takes a fluorescent silicon microsphere probe as a carrier, target protein can be accurately captured, non-specific adsorption is reduced, the function division of an open type flat chip is clear, and the operation is simple and convenient; the traditional detection sensitivity limitation can be broken through, the low-abundance protein is accurately quantified, the background noise interference is reduced, the detection specificity and accuracy are improved, and the early diagnosis of diseases is assisted.

The invention discloses an intelligent early warning method and system for coal and gas outburst based on a T-B cellular immune algorithm. The method comprises the following steps: acquiring various monitoring data in a coal mine; preprocessing the monitoring data to obtain processed data; carrying out dimensionality reduction and local feature value extraction on the processed data by utilizing a deep learning combination model; setting a characteristic value threshold value, and screening the processed data according to the characteristic value threshold value and the local characteristic value to obtain abnormal data and normal data; constructing a T-B cell immune recognition model, and inputting the abnormal data into the T-B cell immune recognition model; and setting an early warning threshold value of the danger level, and outputting the danger level according to the detector type generated by the T cells and the set threshold value so as to realize intelligent early warning of coal and gas outburst. According to the invention, the T-B cellular immune algorithm is creatively combined with a mature underground Internet of Things system, so that the reliability and accuracy of accident early warning are improved.

The invention discloses an engineering cell and application thereof in preparation of a whole-cell tumor vaccine, and belongs to the technical field of biological medicines. According to the engineering cell disclosed by the invention, the form and antigenicity of the tumor cells can be retained through intracellular gelation of the tumor cells, and CD47 blocking and DAMP exposure can enhance the immune recognition capability of the tumor cells and resist immune escape, so that the immunogenicity is improved, and the therapeutic immune response is promoted.

This invention relates to compounds, compositions and methods for treating, reversing or preventing cancer through the modulation of immune responses via Killer-specific Secretory Protein 37 (Ksp37). By enhancing immune recognition, Ksp37 downregulates the checkpoint proteins CD47 and CD24 on abnormal cells, allowing the immune system to effectively identify and eliminate cancerous cells. Additionally, Ksp37 influences cytokine signalling by increasing IL-12 and decreasing IL-2 levels, which supports the activation of natural killer (NK) cells while mitigating chronic inflammation, fostering an immune environment conducive to clearing abnormal cells.

Provided herein are genetically engineered T cells containing a chimeric antigen receptor (CARs), and related methods and uses thereof in allogeneic cell therapy. In some embodiments, the T cells are genetically engineered with a CAR and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are cell compositions containing the engineered T cells, and related methods, kits and systems for producing the engineered T cells. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

The invention discloses a high-affinity anti-human and monkey PCSK9 antibody and application thereof, and belongs to the field of biological medicine. The anti-human PCSK9 antibody comprises a heavy chain variable region of which the sequence is SEQ ID NO.1 and a light chain variable region of which the sequence is SEQ ID NO.2, or a heavy chain variable region of which the sequence is SEQ ID NO.3 and a light chain variable region of which the sequence is SEQ ID NO.4. The six anti-human PCSK9 antibodies are obtained by immunizing mice with human PCSK9 protein and combining with a hybridoma cell line and screening, and can be combined with human PCSK9 with high affinity and high selectivity, so that the combination of the human PCSK9 and LDLR (Low Density Lipoprotein Receptor) on a cytoplasmic membrane is blocked, and the degradation of the LDLR is reduced. PCSK9 is highly expressed in tumors, tumor immune recognition and CD8 + T cell anti-tumor activity are inhibited, and the PCSK9 participates in tumor immune escape. The anti-human PCSK9 antibody provided by the invention can provide candidate antibody molecules for tumor immunotherapy.

A multi-functional near-infrared fluorescent polymer dot (Pdot)-siRNA nanoplatform is disclosed herein. The disclosed technology addresses challenges in siRNA delivery, including poor stability, degradation, and immune recognition, by utilizing positively charged Pdots synthesized from polymers, and electrostatic binding with negatively charged siRNA. The Pdots exhibit dual fluorescence emission at 588 nm and 775 nm, enabling real-time visualization of cellular uptake and siRNA delivery. The nanoplatform demonstrates efficient inhibition of target gene expression, and protein levels in cells. The Pdots provide minimal toxicity and persist in cells for extended periods, offering a robust tool for therapeutic applications, bioimaging, and molecular labeling. This approach combines siRNA delivery with simultaneous imaging, presenting a versatile method for targeted gene regulation and research applications.

Although immune checkpoint blocking (ICB) therapy has significantly improved the prognosis of metastatic melanoma, most patients have not gained long-term benefits. Previous studies show that a part of causes of treatment failure are insufficient immune recognition of tumor antigen (TA). The cancer vaccine can potentially provide a complementary approach to enhance anti-tumor immunity and act synergistically with ICI. Described herein are novel tumor antigens common to most melanoma cells. Several tumor antigens described herein are derived from aberrantly expressed, non-mutated genomic sequences, such as intragene and intergene sequences, which are not expressed in normal tissue. Nucleic acids, compositions, cells and vaccines derived from these tumor antigens are described. The use of the tumor antigens, nucleic acids, compositions, cells and vaccines for the treatment of melanoma is also described.

According to the echinococcus granulosus vaccine based on the self-assembly peptide, a peptide fragment, rich in dominant epitopes, in EgG1Y162-2 is connected to a Q11 amino terminal through '-SGSG-', due to the self-assembly effect of the Q11 peptide, the peptide fragment rich in dominant epitopes is repeatedly expressed on the surface of nanofibers, and therefore EgG1Y162 dominant multi-epitope self-assembly nano-polypeptide is formed; the EgG1Y162 dominant multi-epitope self-assembled nano polypeptide is adopted in the vaccine, so that the immune recognition and response of a body are effectively enhanced.

Provided herein are genetically engineered T cells containing a chimeric antigen receptor (CARs), and related methods and uses thereof in allogeneic cell therapy. In some embodiments, the T cells are genetically engineered with a CAR and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are cell compositions containing the engineered T cells, and related methods, kits and systems for producing the engineered T cells. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

The present invention discloses extracellular vesicles or EVs designed for targeted delivery of bio- therapeutics and gene editing tools, to the cells and tissues. These engineered EVs comprise novel synthetic signal sequences, which facilitate efficient cargo loading. The EVs further comprise specific targeting moieties to locate and attach to target or recipient cells, components to evade immune system detection and potential rejection, inhibit phagocytosis by immune cells, minimize immunogenicity and reduce the likelihood of immune recognition as foreign entities.

The invention discloses a tissue slice target protein multiple analysis method based on reversible DNA self-assembly, comprising step one, design of a DNA self-assembly system, step two, synthesis of an antibody Ab-T, step three, pretreatment and imaging of the target protein of the tissue slice, and step four, image processing of imaging analysis; the invention combines DNA self-assembly system design, click chemistry reaction, immune recognition, reversible DNA self-assembly and tissue fluorescence imaging technology, outputs multiple target proteins on the tissue slice as multiple fluorescence signals, realizes multiple analysis of the target proteins on the tissue slice, reduces time cost and demand for tissue samples without reducing imaging accuracy; and has important significance for basic scientific research, clinical research and application such as spatial localization relationship analysis of multiple target proteins of tissue samples, especially precious tissue samples, cell typing analysis, tissue spatial distribution analysis of cells, etc.

The invention discloses an intelligent artificial bionic DC cell nanoparticle nDC-M and a preparation method, application and a detection method thereof. The nano-particle is of a core-shell structure, the inner core is a hypoxia response type nano-micelle of a sound-sensitive agent SP8 and IL-2 for activating T cells to be mature, the outer layer is coated with a mature DC cell membrane, and the nano-particle has the immune recognition characteristic and the treatment function. In a tumor hypoxic microenvironment, the micelle specifically releases SP8 and IL-2; sP8 generates ROS through ultrasonic excitation, tumor cell immunogenicity death is induced, and antigens are released; iL-2 activates proliferation and functions of tumor infiltration lymphocytes; the outer DC cell membrane and the antigen capture functional group enhance the collection and activation of immune cells through surface antigen presentation, and amplify the anti-tumor immune response. By combining sonodynamic therapy and immunoregulation, tumor growth is inhibited, metastatic load is reduced, good biocompatibility and safety are achieved, and a novel bionic delivery system is provided for metastatic tumor immune combined therapy.

The present application relates to a kind of encoding aspergillus fumigatus chimeric antigen circular RNA and its application, belong to biomedical and vaccine technology field.The present application first applies circular RNA technology to anti-aspergillus fumigatus infection, provides new strategy for fungal vaccine development.Select the non-transmembrane region of aspergillus fumigatus cell membrane protein FtrA to construct antigen, avoid the transmembrane region expression problem and immune recognition uncertainty;Fusion IgK signal peptide and Fc domain, significantly improve antigen secretion efficiency, stability and immune presentation effect.LNP delivery system mature, efficient, can effectively deliver vaccine to host cell and express antigen, the LNP@CircRNA provided by the present application, especially the LNP@CircRNA FtrA2 , can induce high level of IgG antibody and T cell immune response in mouse in vivo without using adjuvant, realize the dual activation of humoral immunity and cellular immunity.

The invention provides a design method for improving the population coverage rate of a multi-epitope vaccine, which comprises the following steps: carrying out epitope prediction on B cells and T cells according to candidate proteins to obtain B cell epitopes and T cell epitopes; setting a sliding window for the candidate antigen protein; judging whether the needed epitope exists in the sliding window or not; if the needed epitope exists, shortening the length of the window by one amino acid, and judging whether the specifically bound MHC-I / II allele is reduced or not; if the MHC-1 / II allele is reduced, the window shortening operation is revoked, and overlapping epitopes which are specifically combined with the maximum MHC-1 / II allele are reserved, so that candidate overlapping epitopes are obtained. According to the invention, a three-type epitope maximization strategy based on a sliding window is adopted, and population coverage rate maximization and dual immune recognition are realized in a vaccine construct with a compact structure by recognizing the number of specific binding MHC-I / II alleles and the number of partially overlapped B cell epitope amino acids.

The present invention relates to a method for calculating binding free energy of an MHC-peptide and a method for screening an MHC-peptide, in which an initial structure of any unknown candidate MHC-peptide is obtained by adjusting amino acids in known MHC-peptide data using a template construction technique. The construction of an accurate MHC-peptide template is the premise of accurately calculating the affinity, and the application adopts a template selection method based on anchor point amino acid and aims to select the template by combining highly conservative structural characteristics of a slot (such as a hydrophobic pocket and an alpha helix-beta-sheet combination). The method is different from a traditional template matching method based on sequence similarity, particularly emphasizes selective binding of head and tail amino acids (anchor point amino acids) of the polypeptide and two ends of an MHC binding slot, and is beneficial to improving the accuracy and reliability of modeling. Compared with the prior art, the application shows powerful performance in the aspect of polypeptide affinity prediction, and lays a foundation for further understanding an immune recognition mechanism and enhancing research on MHC-peptide interaction.

The present invention provides a method for constructing a self-powered photoelectrochemical immunosensor and its application in the detection of genotoxicity markers, which relates to the technical field of chemical biosensors. Based on the specific immune recognition reaction of the genotoxicity marker phosphorylated histone (γH2AX), the present invention uses CdIn2S4 nanospheres as photoanodes, Au as photocathode substrate materials to modify the γH2AX primary antibody (Ab1), and Bi-doped BiOI (Bi-BiOI) nanoflowers to label the γH2AX secondary antibody (Ab2). Through layer-by-layer fixed modification and sandwich immune reaction, a signal amplification type dual-photoelectrode self-powered photoelectrochemical immunosensor is constructed. The sensor constructed by the present invention has a wide linear range and an ultra-low detection limit, which is of great significance for the detection of genotoxicity markers and the screening of genotoxic substances.

The invention discloses a nano-enzyme mediated SERS (Surface Enhanced Raman Scattering) immunodetection method without a Raman nano-label, which can be used for detecting low-concentration biomarkers and improving the sensitivity of SERS detection. The method comprises the following steps: step 1, combining a metal nano-enzyme with a recognition antibody to obtain a nano-enzyme modified by the recognition antibody; combining the capture antibody with an SERS immune substrate to obtain a capture antibody modified SERS immune substrate; step 2, dropwise adding an antigen to be detected on the SERS immune substrate modified by the capture antibody, and incubating; after immune recognition, washing the SERS immune substrate with a PBS buffer solution; nano-enzyme modified by the recognition antibody is dropwise added to the SERS immune substrate and incubated, and the nano-enzyme modified by the recognition antibody and the SERS immune substrate modified by the capture antibody are combined through an antigen; 3, a color developing solution is dropwise added into the SERS immune substrate, and after incubation, quantitative detection is conducted on antigens through a Raman spectrometer.

The invention relates to the technical field of medicines, in particular to a linear nucleic acid structure with a cGAS-STING excitation function and application of the linear nucleic acid structure. According to the invention, a stable DNA nanostructure is designed and synthesized, and is modified by the aptamer, so that the targeting and stability of nucleic acid are improved, and the requirement of activating a cGAS-STING pathway is met. The composite material has good biocompatibility, and can effectively activate an immune system and enhance immune recognition and killing effects on tumor cells. In vitro and mouse tumor models, the prepared nano-carrier can activate the STING pathway, can also significantly improve the tumor immunotherapy effect, and has good preclinical application prospects in the aspects of prolonging the tumor lifetime and slowing down tumor progression. The invention provides a new strategy and technical support for tumor immunotherapy, can be used as a carrier to effectively transfer drugs, and has wide application value.

The invention relates to the technical field of pharmaceutical preparations, in particular to a bionic nano preparation applied to acute diquat poisoning as well as a preparation method and application of the bionic nano preparation. The bionic nano preparation is formed by loading epigallocatechin gallate nano particles on PVA-PLGA (Polyvinyl Acetate-Poly (Lactic-co-Glycolic Acid) nano particles wrapped by an erythrocyte membrane. The bionic nano preparation with a three-layer composite structure is achieved, the purpose of nano preparation escape immune recognition is achieved, and meanwhile the anti-oxidation effect of the medicine is achieved. The preparation method is simple and easy to implement, conditions are controllable, good repeatability is achieved, and the stability of the epigallocatechin gallate can be improved. The prepared erythrocyte membrane bionic EGCG nano preparation has good stability and solubility and can be stored at-20 DEG C for a long time, and the storage life and the service life of the product are prolonged. The nano preparation shows a better diquat detoxification effect, and provides a new drug choice for diquat detoxification.

The invention relates to the technical field of food detection, and specifically discloses a dual-mode magnetic relaxation up-conversion fluorescent biosensor and its application, wherein the dual-mode magnetic relaxation up-conversion fluorescent biosensor comprises an antigen-antibody immune recognition unit, functional magnetic composite nanoparticles and functional up-conversion fluorescent nanoparticles, and the functional magnetic composite nanoparticles and functional up-conversion fluorescent nanoparticles are assembled through the antigen-antibody immune recognition unit to form a dual-mode magnetic relaxation up-conversion fluorescent biosensor for detecting aflatoxin B1 in food. The dual-mode magnetic relaxation up-conversion fluorescent biosensor described in the invention can detect aflatoxin B1 up to 0.16 ng / mL in MR mode and 0.038 ng / mL in FL mode, and the biosensor can ensure detection sensitivity and overcome the interference of colored samples in the detection of aflatoxin B1 in food, thereby effectively improving the accuracy of aflatoxin B1 detection in food.