17 results about "Cross-presentation" patented technology

The invention discloses a DC (dendritic cell) capture type engineering bacterial vaccine for realizing cytoplasm antigen transfer by utilizing gap connection, which is characterized in that attenuated salmonella VNP20009 is utilized to simultaneously express Antigen 4T1-M8 and DC capture peptide CBP-12 to increase contact so as to enhance formation of gap connection between tumor cells and DC and promote delivery of antigen to DC cytoplasm, so that MHC-I mediated cross presentation is enhanced. In addition, as an intracellular bacterium, the VNP20009 can infect tumor cells and colonize in the tumor cells. Therefore, the tumor antigen carried by the VNP20009 can be expressed in cells, so that the tumor antigen can be presented to the surfaces of tumor cells by MHC-I as an endogenous antigen to be recognized by specific CD8 + T cells.

An adjuvant polypeptide, a nano-carrier and application of the nano-carrier in vaccine adjuvant, the present application relates to the field of vaccine.The present application solves the problems of poor antigen compatibility, lack of targeting, low delivery efficiency and insufficient preparation stability of traditional adjuvant.The amino acid sequence of the adjuvant polypeptide Adp is VLGKLAKVAI.The nano-carrier is prepared from the adjuvant polypeptide and antigen.The nano-carrier is prepared by mixing the adjuvant polypeptide and antigen through in-situ radical polymerization.The application of the nano-carrier in vaccine adjuvant.The present application screens a new vaccine adjuvant by bioinformatics method, so that it has the abilities of dendritic cell targeting and intracellular STING pathway activation, thereby enhancing the cross-presentation of antigen.Based on this, the new adjuvant is coupled with monomer, and an intelligent vaccine delivery system is constructed by in-situ polymerization method, so as to realize the efficient delivery of tumor cell membrane protein antigen and improve the immunotherapy effect of tumor vaccine.

The application discloses an engineered potent dendritic cell vaccine and a preparation method and application thereof, and utilizes a nano-scale antigen delivery mode to fuse tumor antigens with cationic liposomes, destroys the stability of a lysosome membrane by means of cationic liposome charge interaction, makes part of the antigens escape into a cytoplasm to be cross-presented through an MHC I pathway, gives the DCs the ability to activate a cellular immune response to resist tumors, on the other hand, gives the DCs T cell directivity through a synthetic immunology method, promotes the interaction and signal transmission of DC-T cells, and the combination of the two mechanisms can overcome the low response rate problem of the existing DC vaccine, and maximizes the anti-tumor immune response.

The present application relates to the technical field of nano-vaccine, and particularly relates to fluorinated or alkylated polyaspartic acid, a preparation method thereof and application thereof in vaccine delivery. The fluorinated or alkylated polyaspartic acid has a structure shown in formula I. The fluorinated or alkylated N-substituted polyaspartic acid provided by the present application has excellent self-assembly capacity, and has good biocompatibility and low cytotoxicity. In the preparation of a nano-vaccine, the loaded antigen can be co-assembled into nanoparticles with the fluorinated or alkylated polyaspartic acid through hydrophobic interaction. In addition, the fluorinated or alkylated N-substituted polyaspartic acid retains the high cell uptake and endosome escape level of the N-substituted polyaspartic acid itself. Therefore, the fluorinated or alkylated N-substituted polyaspartic acid can enhance antigen uptake and promote cross-presentation.

A multi-target DC vaccine based on tumor antigen epitope peptides and its application belong to the field of tumor immunotherapy technology. The vaccine comprises an hr-8 conjugate peptide, an immune adjuvant, a carrier, and an immune memory enhancer. The hr-8 conjugate peptide is a conjugate product formed by chemically linking an hr-8 targeting peptide with at least two different tumor antigen CTL epitope peptides. The immune adjuvant is a combined adjuvant system of the TLR9 agonist CpG ODN and the TLR3 agonist poly(I:C). The carrier is PLGA nanoparticles, and the immune memory enhancer is IL-7 and / or IL-15. This invention utilizes the specific binding of the hr-8 peptide to the DEC-205 receptor on the surface of dendritic cells to achieve efficient synergistic delivery and cross-presentation of multi-target antigens. The combined adjuvant and memory factor significantly enhance CTL activation and promote long-term immune memory formation, giving the multi-target DC vaccine advantages such as strong targeting, broad antigen coverage, and prolonged relapse-free survival.

The invention discloses TIM-3 scFv bionic nanoparticles loaded with an A-D-A organic sound-sensitive agent and a preparation method and application of the TIM-3 scFv bionic nanoparticles loaded with the A-D-A organic sound-sensitive agent. The preparation method comprises the steps that a tetrahydrofuran solution of CH-H and a tetrahydrofuran solution of DSPE-PEG are added into deionized water, ultrasonic treatment is carried out, then rotary evaporation is carried out, concentration and drying are carried out, and the A-D-A organic sound-sensitive agent nanoparticles are obtained; the method comprises the following steps: obtaining a cell membrane of a macrophage with stable overexpression of an EGFP-TIM-3 scFv gene, then mixing the cell membrane with A-D-A organic sound-sensitive agent nanoparticles, and extruding through an extruder; the organic sound-sensitive agent can efficiently generate ROS and can directly kill tumor cells and induce ICD, meanwhile, TIM-3 scFv blocks TIM-3 signals on cDC1 cells, the antigen presentation function of the cDC1 cells is recovered, positive feedback circulation of sonodynamic killing, antigen release, cross presentation and T cell activation is formed, and the aim of treating colorectal cancer is achieved.

The present invention relates to a FLT3L–flagellin hybrid adjuvant with enhanced antigen cross-presentation efficacy and a vaccine composition comprising same. The hybrid adjuvant of the present invention demonstrated significant therapeutic efficacy as an adjuvant for a therapeutic cancer vaccine in a preclinical mouse model of cervical cancer, resulting in complete tumor regression and sustained protection. In addition, the hybrid adjuvant of the present invention induced tumor-specific antigen CD8+ T cell responses and progenitor-exhausted CD8+ T cells (Tpex) due to an increase in cross-presentation by conventional type 1 dendritic cells (cDC1) in tumor-draining lymph nodes and the tumor microenvironment, and the combination of TCV having the hybrid adjuvant applied thereto and anti-PD-1 therapy significantly improves survival outcomes in anti-PD-1–resistant tumors, and thus can be advantageously applied in anticancer immunotherapy using therapeutic cancer vaccines.

The invention provides a 3, 5, 6-trimethylbenzofuran-2-ketone derivative and application thereof in STING activation, and the derivative has a structure as shown in a formula (I) and a formula (IV). In the prior art, through a strategy of knocking out STIM1 through CRISPR-Cas9, although cGAMP-mediated I-type interferon secretion is improved, intracellular calcium ion concentration is remarkably reduced due to irreversibility of knockout, calcium ion balance is destroyed, and processes of subsequent antigen cross presentation and the like are not facilitated. According to the present invention, the small molecule is developed to achieve the separation of STIM1 and STING, and the intracellular calcium ion steady state is maintained while the STING endoplasmic reticulum retention is removed so as to effectively enhance the tumor treatment effect of the STING agonist, and particularly, compared with the STING agonist previously disclosed by the applicant, the reported compound has characteristics of strong STING sensitivity enhancing ability, good STING sensitivity enhancing effect, and good tumor treatment effect. Meanwhile, good anti-tumor activity and anti-inflammatory activity are achieved, and the clinical immune response rate is expected to be remarkably improved.

The invention relates to application of an ATG5-dependent STING activator to treatment of melanoma, simvastatin or pharmaceutically acceptable salt thereof is used for preparing a medicine for activating a cGAS-STING pathway and remodeling a melanoma immune microenvironment, dendritic cell maturation and antigen cross presentation are promoted, CD8 T cells are activated, the infiltration level of the CD8 T cells and the secretion ability of IFN-gamma and TNF-alpha are improved, and the melanoma immune microenvironment is improved. Meanwhile, the expression of depletion marker proteins PD-1, TIM3 and CD39 is down-regulated, so that the conversion from immune cold tumors to thermal tumors is realized. By activating a key cGAS-STING pathway in the dendritic cells, death of immunogenic cells can be efficiently induced, and maturation and antigen presentation of the dendritic cells are promoted, so that cold tumors are converted into hot tumors, the problem of drug resistance in immunotherapy is solved, and anti-tumor immune response is improved.

This invention discloses a graph reasoning and analysis system for addressing defects in cellular antigen processing, belonging to the field of knowledge graph reasoning technology, to solve the problem of slow interpretable localization of defect presentation. This invention constructs a detection likelihood set by integrating HLA typing, somatic cell variation, transcriptomic expression, immunopeptidomics, and surface HLA detection. It assembles direct and cross-presentation subgraphs using pattern gating and loading complex integrity rules, generating reachable paths and observation consistency matrices. It distinguishes between structural contradictions and detection limitations, performs node pruning and link contraction based on constraint propagation to form an individualized graph, and outputs defective nodes and paths based on minimum interpretable paths and causal graph cost search. It generates validation and intervention lists and clinical decision support outputs, thereby reducing unnecessary detection and intervention attempts and improving the timeliness and consistency of case analysis and strategy formulation.

@biotinThe invention discloses a preparation method and application of a lipid bispecific antibody nanosheet capable of activating a cGAS-STING pathway to enhance anti-tumor immune response of cDC1 and PD-1 + T cells in the field of biological medicine, and the preparation method comprises the following steps: firstly, preparing an Mg0.2 Co0.8 (OH) 2 nanosheet, then wrapping the prepared Mg0.2 Co0.8 (OH) 2 nanosheet with liposome, then coupling biotin with a monoclonal antibody, and finally preparing the lipid bispecific antibody nanosheet capable of activating the cGAS-STING pathway to enhance the anti-tumor immune response of the cDC1 and PD-1 + T cells. Streptavidin is coupled with lipidosome of a nano cobalt magnesium tablet, LMC is finally fused with alphaCLEC9A (at) biotin and alphaPD-1 (at) biotin, Co < 2 + > and Mg < 2 + > released by MC enter cytoplasm, a cGAS-STING pathway is synergistically activated, DC is promoted to secrete IFN-1 and costimulatory molecules, and the antigen presentation capacity is enhanced; the bispecific antibody is combined with CLEC9A + cDC1 and PD-1 + T cells at the same time, promotes physical crosstalk of the CLEC9A + cDC1 and PD-1 + T cells in tumors and drainage lymph nodes, and activates CD8 + T cells to proliferate and differentiate into effector T cells; in a TC-1 tumor-bearing mouse, LMC-NBiE promotes CD8 + T cell infiltration and tumor cell apoptosis and inhibits tumor growth by inducing high expression of CLEC9A + cDC1 and cross presentation of tumor antigens.

The invention belongs to the technical field of biomedicine, and relates to an exosome vaccine as well as a preparation method and application thereof, and the exosome vaccine is an exosome which expresses coexistence of CCL19 full-length CDS and neoantigen through lentivirus construction by utilizing HEK-293 FT cells. According to the exosome vaccine, antigen presenting cells are targeted in a CCL19-CCR7 receptor-ligand mediated targeted delivery mode, the antigen presenting cell uptake and delivery efficiency of the Neo-CCL19Exos vaccine is improved, MHC-I dependent antigen cross presentation is efficiently activated, TLS formation in liver cancer is promoted, liver cancer is induced to be converted from cold tumor to hot tumor, and liver cancer is induced to be cured. Therefore, a novel method is provided for designing vaccines and enhancing the immune curative effects of the vaccines in the future.

The present invention provides a recombinant multivalent TREM1 agonist, termed Tetra-CNX, designed to engage and activate TREM1 on myeloid cells. The ligand comprises multiple calnexin luminal domains assembled in a multimeric configuration, enabling high-avidity receptor binding and downstream SYK-dependent signaling. Upon activation, Tetra-CNX enhances lysosomal remodeling and promotes efficient antigen uptake, processing, and presentation via MHC class I and II pathways. This invention enables improved priming of CD4+ and CD8+ T cells and facilitates immune activation in contexts requiring enhanced antigen presentation, including but not limited to cancer, infectious diseases, and vaccine responses. Pharmaceutical compositions and methods of use are provided for modulating myeloid cell function and adaptive immunity through TREM1-targeted intervention.

The invention relates to the crossing field of biological nanometer technology, immune engineering and drug delivery, and discloses a topological structure programmable antigen delivery system based on a DNA nanometer frame and a construction method of the topological structure programmable antigen delivery system. The antigen delivery system comprises at least one DNA nano frame with a specific three-dimensional topological structure; the antigen molecule and / or the immunologic adjuvant are / is accurately modified on the DNA nano-framework through covalent or non-covalent interaction; wherein the topological structure of the DNA nano framework is selected from at least one of a small icosahedron framework S-DIF, a truncated icosahedron framework DSF, an octahedron framework DOF and a large icosahedron framework L-DIF. According to the invention, the rational association between the carrier topology and the immune function is realized, the efficiency bottleneck of cross presentation is broken through, a multifunctional integrated platform with synergistic interaction is provided, and the DNA material is natural and degradable, has high biocompatibility, and has high efficiency and biological safety.

The application belongs to the field of genetic engineering, and discloses a recombinant protein and application thereof in malaria transmission blocking. In the present application, geap36 is coupled with AP205 by using SpyTag-SpyCatcher reaction. The technology is novel at present, and is different from traditional malaria vaccines which only use proteins expressed in a certain stage of Plasmodium as immunogens. Due to the addition of AP205 protein, the AP205 protein can self-assemble into virus-like particles (VLP) when overexpressed, and can carry antigen fragments, which is beneficial to the uptake and cross-presentation of antigen-presenting cells. In the experiment, geap36 is selected as the coupled antigen, and an experimental group and a control group are established, so as to evaluate whether the VLP vaccine formula can improve the immunogenicity of geap36 and reduce the transmission activity (TRA), and provide a reference for subsequent vaccine research.

The invention provides a system and a method for inducing generation of Bst2 + B cells and application of the system and the method. The system for inducing to generate the Bst2 + B cells comprises a basic culture medium and an oncolytic virus M1. The system can be used for inducing B cells in a marginal region to generate Bst2 + B cells, and the Bst2 + B cells have the effect of cross-presenting tumor antigens to activate tumor specific CD8 + T cells. Furthermore, a glioma B cell deficient mouse model is constructed, the curative effect of the Bst2 + B cells is verified, and the Bst2 + B cells are found to be capable of remarkably prolonging the survival of the mouse.

The invention discloses an atlas inference analysis system for cell antigen treatment defects, relates to the technical field of knowledge atlas inference, and is used for solving the problem of slow explaining and positioning of defect presentation. According to the method, a detection likelihood set is constructed by fusing HLA typing, somatic cell variation, transcriptional expression, immunopeptidomics and surface HLA detection, direct presentation and cross presentation sub-graphs are assembled by adopting a mode gating and loading complex integrity rule, a reachable path and observation consistency matrix is generated, structural contradictions and detection limitations are distinguished, and a detection result is obtained. According to constraint propagation, node cutting and link shrinkage are performed to form an individualized map, defect nodes and defect paths are searched and output based on a minimum interpretation path and a cause and effect graph cost, and a verification and intervention list and clinical decision support output are generated, so that unnecessary detection and intervention attempts are reduced, and the detection efficiency is improved. And the timeliness and consistency of case analysis and strategy making are improved.