117 results about "Immunoresponse" patented technology

The invention relates to the technical field of biological medicine, in particular to cat allergen fusion protein, an mRNA immune preparation and application of the cat allergen fusion protein and the mRNA immune preparation. The amino acid sequence of the cat allergen fusion protein disclosed by the invention is as shown in SEQ ID NO.11. The cat allergen fusion protein provided by the invention is a fusion protein obtained by fusing key segments with strong sensitization of Fel d2 and Fel d4 proteins with Fel d1 full-length protein, the fusion protein can simultaneously cover main sensitization epitopes of Fel d1, Fel d2 and Fel d4, and the sensitization effect of cat allergens can be more comprehensively blocked. According to the cat allergen fusion protein provided by the invention, an mRNA immune preparation can be rapidly designed and synthesized, the expression of the cat allergen fusion protein can be accurately controlled in poultry bodies, the immunoreaction is more durable, and the prepared IgY antibody can effectively block allergic protein in cat oral saliva.

The invention relates to the technical field of tumor prognosis prediction, in particular to a chest tumor prognosis prediction method and system based on data analysis, and the method comprises the following steps: S1, data collection: collecting multi-modal data of a chest tumor patient; s2, data preprocessing: preprocessing the collected multi-modal data; s3, prediction of tumor immune cell infiltration: predicting the infiltration degree of tumor immune cells, and evaluating the influence of the infiltration degree on patient prognosis; and S4, prognosis analysis and prediction: performing comprehensive analysis through a multi-layer perceptron algorithm to generate prognosis prediction results of the tumor patient, including tumor metastasis risk, recurrence probability and immunotherapy response. According to the invention, the complexity of the tumor immune microenvironment can be better captured, so that more accurate prognosis evaluation is provided, and clinical doctors are helped to understand the potential influence of immune response on tumor metastasis, recurrence and immunotherapy response.

The invention discloses a high-strength low-immunoreaction bone bonding material and a preparation and application method thereof. The bone binding material comprises tetracalcium phosphate, serine phosphate, magnesium phosphate and a sodium citrate solution. According to the preparation method, tetracalcium phosphate, phosphoserine, magnesium phosphate powder and a sodium citrate solution are fully mixed and reacted by utilizing a hedging device consisting of a screw injector and a connecting pipe. And extruding the mixed liquid material through a filter membrane to complete the preparation of the bone adhesive material. The bone binding material can be used for preparing bionic sclerotin, binding broken bones in comminuted fractures or smearing the bone binding material to bone gaps, and in the decomposition process, the bone binding material can continuously release magnesium ions, so that the immune environment of early bone repair is regulated and controlled, the bone repair process is accelerated, and bone healing is promoted. Meanwhile, experimental data prove that the bone adhesive material provided by the invention can provide stable supporting strength, has no potential toxicity to fibroblasts, and is good in biocompatibility.

The invention discloses an HLA and antigen peptide combination prediction method based on interactive attention, and belongs to the technical field of computational biology. The method comprises the following steps: 1, collecting HLA allele and unique peptide fragment data, and constructing an HLA and antigen peptide binding data set; 2, constructing an HLA and antigen peptide binding prediction model, and training the prediction model by using the HLA and antigen peptide binding data set to obtain a trained prediction model; and step 3, inputting the HLA sequence and the antigen peptide sequence into the prediction model to obtain a prediction result of combination of the HLA and the antigen peptide. According to the method, prediction tasks based on a sequence and a structure are integrated into a unified model, and the potential of the pHLA about the sequence and the structure is analyzed and predicted. Compared with an existing method, the two-dimensional evaluation provides a more comprehensive antigen immunogenicity view angle, and a new insight is provided for the quality of a new antigen for triggering an immunoreaction.

The invention relates to a porcine reproductive and respiratory syndrome virus (PRRSV) dimer nucleocapsid (N) protein (PRRSV N-dimer) and application thereof. The PRRSV N-dimer is formed by connecting N protein amino acid sequences in series through (GGGGS) 3linker. According to the invention, a GGGGS 3linker nucleotide sequence is connected in series with a PRRSV NADC30-like strain N protein gene sequence to construct a prokaryotic expression vector, and a recombinant PRRSV N-dimer is expressed in escherichia coli. Through SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis) and Western-blot detection, the recombinant PRRSV N-dimer obtains soluble expression and can be subjected to a specific reaction with PRRSV positive serum; through detection by a freeze thawing method and an ELISA (Enzyme-Linked Immunosorbent Assay) method, compared with a PRRSV monomer N protein (PRRSV N-monomer), the PRRSV N-dimer protein can be stably preserved, and the immunoreactivity is better. A PRRSV antibody indirect enzyme-linked immunosorbent assay (iELISA) detection method is established on the basis of a PRRSV N-dimer, and can be applied to diagnosis and monitoring of PRRSV infection.

The invention provides an anti-influenza A virus nano antibody and application thereof, the nano antibody comprises a heavy chain variable region, the heavy chain variable region comprises CDR1, CDR2 and CDR3, and the CDR3 of the heavy chain variable region is selected from an amino acid sequence as shown in SEQ ID NO: 8 or SEQ ID NO: 16. The anti-influenza A virus nano antibody can be combined with various influenza A viruses, including subtype influenza viruses such as H1N1, H2N2, H3N2 and H7N9, has strong broad spectrum, has different binding epitopes of the two nano antibodies, and can be applied to double antibody sandwich method detection, enzyme-linked immunosorbent assay and colloidal gold detection. According to the invention, multivalent transformation is also carried out on the nano antibody to obtain a dodecavalent hexamer cyclic structure nano antibody, so that the application scene of the anti-influenza A virus nano antibody can be further extended.

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 relates to the technical field of vaccines, in particular to an activity detection method of an HPV (human papilloma virus) trivalent therapeutic vaccine. The method comprises the following steps: inoculating and infecting BEAS-2B cells by adopting constructed HPV16 / 18 / 52 type E6 / E7 antigen-loaded non-replicating type 5 adenovirus, culturing, extracting total protein, sequentially performing SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis), western blot detection, immunoreaction and developing imaging, and detecting the fusion protein; the transfection complex number MOI of the constructed adenovirus is 15-25, and the convergence degree of BEAS-2B cells is greater than 80%; the membrane transfer current of the western blot method is 220-280 mA, and the time is 50-80 minutes. The method avoids the problem of inaccurate detection results caused by obvious difference of biological activities in different animal species, has good accuracy, stability and durability, is simple in steps and low in cost, and can be effectively popularized and used.

The invention belongs to the field of biological immunity, and discloses a linear B cell epitope of African swine fever virus NP419L protein and application. The epitope sequence shows good immunoreactivity through ASFV positive pig serum recognition verification. The African swine fever positive serum can be identified by using the B cell epitope identified by the invention to carry out ELISA (Enzyme-Linked Immunosorbent Assay) experiment, and the sensitivity of the African swine fever positive serum is superior to that of NP419L protein full length and other truncated fragments. The epitope identified by the invention has high conservative property in reference ASFV strains in a plurality of popular regions in China, and has wide universality and adaptability. The kit can be widely applied to etiological diagnosis, serological diagnosis, immunological detection and disease prevention and treatment of African swine fever viruses, and can be applied to preparation of African swine fever vaccines, pathogenesis research and the like.

The invention discloses a broad-spectrum coronavirus protein chimeric nanoparticle vaccine as well as a preparation method and application thereof. The coronavirus protein chimeric nanoparticle vaccine provided by the invention is a protein nanoparticle formed by self-assembly of a glycosylated and modified coronavirus RBD sequence, a glycosylated and modified coronavirus HRC, a glycosylated and modified DN5B sequence and a glycosylated and modified DN5A sequence. The vaccine can induce an organism to generate broad-spectrum immunoreactions aiming at various coronaviruses and variants thereof, so that a new solution is provided for dealing with spreading, prevention and control of the coronaviruses, and a technical foundation is laid for prevention of new variants of the coronaviruses possibly occurring in the future.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The invention discloses a tumor vaccine of a targeted delivery system and a preparation process of the tumor vaccine, and belongs to the field of biological medicine, the tumor vaccine comprises a self-assembled nano-carrier, the self-assembled nano-carrier is formed by self-assembling a biodegradable polymer and an amphiphilic block copolymer, and the self-assembled nano-carrier can be spontaneously assembled into a nano-structure in an aqueous solution according to environmental conditions; the multiple targeting molecules are combined on the self-assembled nano-carrier, and the targeting molecules comprise at least one of a tumor specific antibody, a tumor vascular endothelial growth factor receptor ligand and an aptamer of tumor cell surface overexpression protein; the delivery efficiency of the tumor vaccine is remarkably improved by the multi-targeting mechanism and the optimized nano-carrier; the immunoreaction intensity is effectively improved; the traditional multi-step synthesis is simplified into one-step rapid synthesis through a preparation process combining an ultrasonic-assisted solvent evaporation method and a microfluidic liquid-liquid phase distribution method, so that the production time is shortened.

The invention belongs to the technical field of cancer immunotherapy, and particularly relates to iterative radiation-resistant tumor cell debris, a preparation method thereof and an application thereof in tumor resistance. The anti-radiation tumor cells generated by repeated radiation exposure show higher TMB (Tetramethylbenzidine) and induce stronger immunoreaction, so that a personalized vaccine is developed based on the method, and the frozen fragment vaccine is obtained by freeze thawing and inactivation of the radiation-resistant tumor cells. The RR-FDV exhibits enhanced immunogenicity as compared to a conventional radiosensitive counterpart. In the present disclosure, RR-FDV exhibits superior activation of antigen presenting cells, while in vivo, it recruits more dendritic cells to the vaccination site, promotes DC-mediated antigen presentation, and induces stronger antigen-specific T cell toxicity.

The invention discloses an AAV2 recombinant gene system for double expression of sFLT-1 and shVEGF as well as a preparation method and application of the AAV2 recombinant gene system, and co-expression of the sFLT-1 and the shVEGF is realized. A target gene (sFLT-1: NM001159920.2, shVEGF: NM001025366.3) is cloned to a pAAV-CMV vector through BamHI, HindIII, EcoRI and MluI sites, a pAAV-CMV-sFLT-1-shVEGF plasmid is constructed, and the plasmid is subjected to PCR (Polymerase Chain Reaction), enzyme digestion and sequencing verification, so that the recombinant plasmid is obtained. And then, co-transfecting HEK293 cells with pAAV-RC2 and pHelper plasmids to produce rAAV particles, carrying out gradient ultracentrifugation purification on the rAAV particles by virtue of iodo-pentose, and storing the rAAV particles at the temperature of 80 DEG C below zero. The AAV2 recombinant gene system has the following advantages that the sFLT-1 and the shVEGF are stably expressed, the immunoreactivity is low, and the AAV2 recombinant gene system for double expression of the sFLT-1 and the shVEGF plays a role for a long time, so that the AAV2 recombinant gene system for double expression of the sFLT-1 and the shVEGF can be applied to various neovascularization diseases.

To provide immunoresponsive cells having IL-1 superfamily activities with spatiotemporal restriction.SOLUTION: The present invention provides an immunoresponsive cell expressing a modified pro-cytokine of the IL-1 superfamily, where the modified pro-cytokine comprises, from N-terminus to C-terminus, (a) a pro-peptide; (b) a cleavage site recognized by a protease other than caspase-1, cathepsin G, elastase or proteinase 3; and (c) a fragment of a cytokine of the IL-1 superfamily.SELECTED DRAWING: None

The invention discloses a tumor immunoreactivity detection kit, and relates to the technical field of detection kits.The tumor immunoreactivity detection kit comprises a kit body, one end of the kit body is rotationally connected with a top cover through a kit body opening and closing assembly, a detection panel is arranged in the kit body, and a reagent detection assembly used for tumor immunoreactivity detection is arranged on the detection panel; an opening and closing plate assembly is arranged at the other end of the box body; a reagent or a sample is sucked through a rubber head dropper in the reagent detection assembly for tumor immunoreactivity detection, the interior and the exterior of the rubber head dropper are synchronously disinfected and cleaned through the dropper disinfecting and cleaning mechanism, a top cover and a box body are sealed through the box body opening and closing assembly, and one end of the box body is sealed through the opening and closing plate assembly. The opening and closing plate is opened so as to transport reagents or samples in the kit body, or the opening and closing plate is opened so as to directly take out and replace the reagent detection area after detection from the outside of the kit body; the device has the advantages of being convenient to use, good in sealing performance, capable of saving resources, good in safety and convenient to transport.

The invention relates to the technical field of cell-loaded biological medicine, in particular to a novel efficient nucleic acid delivery method of a carrier siRNA (small interfering Ribonucleic Acid) medicine, which comprises the following steps: constructing a multifunctional nano-carrier taking a biodegradable polymer as a core, the surface of a multifunctional nano-carrier is modified with a targeting ligand, through specific binding of the targeting ligand and a vascular endothelial cell surface receptor and reversible adjustment of penetration promoting molecules on tight connection, the siRNA / carrier compound can efficiently penetrate vascular endothelium including a blood brain barrier, and meanwhile, the siRNA / carrier compound has the advantages that the targeting ligand can be used for preparing a targeted medicine for treating vascular endothelial cells, and the targeted medicine can be used for treating vascular endothelial cells. According to the present invention, the nucleic acid delivery efficiency is significantly improved, the siRNA can be massively delivered into the tumor or the specific tissue cell due to the precise targeting and the efficient penetrating power, and the selected biodegradable polymer and the selected modification molecule have good biocompatibility so as not to cause the obvious immunoreaction and toxicity in the body.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The invention discloses a polyclonal antibody targeting a human CPNE7 variable splicing isomer and application of the polyclonal antibody, and belongs to the technical field of biological medicine. The antigen epitope 'KYKQKRRSYKN' (SEQ ID NO.1) capable of being targeted by the polyclonal antibody provided by the invention is positioned in a common conserved region of all main isomers of CPNE7, and a variable splicing region is not involved. The titer of the obtained antibody serum is as high as 1: 32,000, which indicates that the antibody has extremely high immunoreactivity and sensitivity and can be used for detecting trace proteins. The antibody disclosed by the invention can be used for effectively identifying GST-CPNE7 fusion protein expressed by a prokaryotic system and CPNE7-FL and CPNE7-S protein overexpressed in an eukaryotic system (A549 cells), and the applicability of the antibody in various experimental systems is proved. Therefore, the blank in the prior art can be filled, and a core tool is provided for research of the CPNE7 in the fields of tumor biology, diagnosis and treatment.

To provide a protein adsorption inhibitor that can suppress the adsorption of proteins to surfaces such as immunoreaction vessels and measuring instruments to a high degree, while also reducing variability between measurements. [Solution] Formula (1): Z-{O-[(PO) a (EO) b ]-(AO) c -H]} x A protein adsorption inhibitor comprising an alkylene oxide derivative represented by (the definition of the symbols in the formula is as described in the specification), wherein the cloud point of a 1% by mass aqueous solution of the alkylene oxide derivative is 0°C or higher and 30°C or lower.

This application relates to the field of tumor metabolic biomarker detection technology, and discloses a method for detecting glucose metabolism biomarkers in esophageal cancer based on VAV2-related molecular characteristics. The method includes: performing immunohistochemical staining on esophageal cancer tissue samples to obtain VAV2, EIF3F, MTA1, and HIF-1α protein expression sections; scoring the immunoreaction of each section; calculating a comprehensive glucose metabolism phenotype score based on the molecular hierarchy of the VAV2-EIF3F-MTA1 / HIF-1α glucose metabolism regulatory pathway; and classifying the samples into high-glycolytic, moderate-glycolytic, and low-glycolytic types according to the comprehensive score. This application improves the accuracy and stability of glucose metabolism phenotype discrimination in esophageal cancer.

The invention belongs to the field of molecular biology and clinical medicine, and relates to an IGF-1R targeting nucleic acid aptamer and application thereof. The nucleic acid aptamer of the target IGF-1R comprises any one nucleotide as shown in SEQ ID NO. 3 to SEQ ID NO. 4. The nucleic acid aptamer of the target IGF-1R comprises any one nucleotide as shown in SEQ ID NO. The nucleic acid aptamer disclosed by the invention can be massively synthesized in vitro, and is low in price, good in stability, high in affinity, convenient to store and easy to edit; meanwhile, the molecular weight is small, immunoreaction is not easy to occur, and the single-stranded DNA is good in chemical stability, reversible in denaturation and renaturation and easy to store for a long time and transport at room temperature.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

The invention relates to the technical field of tumor immunotherapy, in particular to an HLA restrictive neoantigen polypeptide based on malignant ascites tumor cells and application of the HLA restrictive neoantigen polypeptide. The invention provides cholangiocarcinoma neoantigen polypeptide. The amino acid sequence of the neoantigen polypeptide is shown as SEQ ID NO.1, 2 or 3. The tumor neoantigen polypeptide is separated and screened from malignant ascites of a biliary duct cancer patient, has high affinity with HLA molecules, can stimulate generation of tumor specific T cells, further generates immune response of targeted tumor cells, can be used as a target spot for clinical treatment or diagnosis of tumors, and has good application prospects. Good application prospects are realized in tumor immunotherapy.

The invention discloses a preparation method and application of an intelligent nano regulator for tumor photoimmunotherapy, and belongs to the technical field of fine chemical engineering. The intelligent nano regulator is formed by assembling an amphiphilic polymer modified by an immunologic adjuvant Resiquimod (R848) and biotin and a small molecule photosensitizer Try5-Ph-3F together. The nano regulator can be effectively taken by cancer cells and positioned in endoplasmic reticulum, and has good tumor targeting ability. Under illumination, the photosensitizer generates a large amount of reactive oxygen species (ROS) to cause endoplasmic reticulum aggression so as to promote release of immune injury related molecular patterns (DAMPs) and promote maturation of dendritic cells (DCs), in addition, R848 is released in a tumor slightly acidic environment, and maturation of DCs is promoted. And the two drugs cooperate to promote the outbreak of immune response, so that the host obtains stronger and longer-time anti-tumor ability.

The invention provides an enterobacter carrying a CD176 antigen and application thereof, the 16S rRNA gene sequence of the enterobacter has 99% consistency with the 16S rRNA gene sequence of Escherichia coli, the enterobacter can express the CD176 antigen and generate a CD176 antibody through immune induction, and the enterobacter is preserved in the China General Microbiological Culture Collection Center (CGMCC) with the preservation number of CGMCC No.27745. The bacterium can be used as an antigen for inducing CD176-targeted immunoreaction, can be used as an engineering bacterium, and has wide application.

The invention discloses a method for co-immunoculture of patient-derived tumor cell antigen peptide loaded by PBMC (peripheral blood mononuclear cells) and autologous DC (dendritic cells) and application of the method. The method comprises the following steps: extracting tumor-associated antigen peptide from a patient-derived tumor organ (PDO), and performing IFN-gamma pretreatment and freeze-thaw cycle purification; separating CD14 < + > mononuclear cells from the PBMC, inducing mature DCs (Dendritic Cells) by adopting a two-stage culture method, and loading antigens; and co-culturing the PBMC and the antigen-loaded DC, and detecting IFN-gamma expression after culturing for 48 hours. According to the method, the sensitivity and consistency of immunoreaction are remarkably improved, the experimental period is shortened, and the method is suitable for individualized drug screening and tumor immunity research.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The invention discloses a preparation method and application of a PSA-ACT compound recombinant protein. The preparation method comprises the following steps: obtaining gene segments of recombinant PSA and ACT proteins; respectively connecting the gene segments to starting vectors to form corresponding connectors; carrying out conversion and screening operation on the linker to obtain a corresponding recombinant plasmid; carrying out transformation, transfection, induction and fermentation broth separation and purification operation on the recombinant plasmid to obtain recombinant PSA and ACT proteins; then activating PSA recombinant protein by using metalloproteinase, and then mixing ACT with the activated PSA to obtain a mixture containing the PSA, ACT and a PSA-ACT compound; and finally, purifying by using an ion exchange chromatography technology and a hydrophobic chromatography technology in sequence to obtain the high-purity and high-activity PSA-ACT compound. According to the method, the spontaneous reaction of ACT and activated PSA is utilized, other chemical cross-linking agents are not needed, the cost can be reduced, and the recombinant protein can be produced on a large scale; the PSA-ACT recombinant protein prepared by the method disclosed by the invention has very strong immunoreactivity.

Described herein are compositions and methods for regulating expression of effector molecules using engineered macrophage-specific promoters. Immunoresponsive cells (such as macrophages) comprising the same are also described.