206 results about "Immune escape" patented technology

The invention discloses a bispecific nano antibody targeting CXCL1 and PD-L1 and application thereof, and belongs to the technical field of antibody engineering and bioengineering. The bispecific nano-antibody targeting CXCL1 and PD-L1 comprises at least one nano-antibody for recognizing a target CXCL1 and a nano-antibody for recognizing a target PD-L1, and nano-antibody monomers are connected through a linker. The bispecific nano-antibody targeting PD-L1 / CXCL1 provided by the invention has a unique structure, so that the bispecific nano-antibody targeting PD-L1 / CXCL1 has specific recognition and binding capacities to CXCL1 and PD-L1, the affinity to CXCL1 reaches 1.08 nM, the affinity to PD-L1 reaches 1.09 nM, drug resistance of a patient to antibody treatment caused by immune escape can be effectively prevented, and the bispecific nano-antibody targeting PD-L1 / CXCL1 is suitable for more patients and has good clinical application prospects. And a new thought is provided for CRC treatment.

The invention provides an H1N1 broad-spectrum mRNA (messenger ribonucleic acid) vaccine taking HA (hemagglutinin) and NA (neuraminidase) protein tandem as a target and a preparation method of the H1N1 broad-spectrum mRNA vaccine, and relates to the technical field of vaccine preparation, the amino acid sequence of the mRNA vaccine is shown as SEQ ID NO.1, and the nucleotide sequence of the mRNA vaccine is shown as SEQ ID NO.2, namely, the mRNA vaccine is obtained by connecting GGGSGGSGGGSGGGGS with conserved amino acid sequences of hemagglutinin HA and neuraminidase NA. The defects in the prior art are overcome, and the broad spectrum and the protection effect of the vaccine are improved, so that the vaccine can better cope with the immune escape of the latest variant in the future.

The invention relates to the technical field of medical care informatics, in particular to a respiratory infectious disease risk early warning method and system. The method comprises the following steps: acquiring a respiratory tract sample of a mutant virus infected person; the method comprises the following steps: extracting a mutant virus from a respiratory tract sample, carrying out genome sequencing on the mutant virus, positioning starting and ending positions of a spike protein coding gene in a genome by virtue of a biological information comparison method, extracting a spike protein coding sequence, and translating the spike protein coding sequence into an amino acid sequence; inputting the amino acid sequence into an immune escape prediction model to predict the immune escape score of the mutant virus; and performing risk assessment based on the immune escape score in combination with clinical monitoring information, and outputting a respiratory infectious disease risk early warning value. According to the invention, the risk of respiratory infectious diseases can be early warned better.

The invention relates to a hepatocellular carcinoma gene knockout target library based on multiple omics and a screening method of the hepatocellular carcinoma gene knockout target library, and the gene knockout target library for precise treatment of hepatocellular carcinoma is finally obtained through data collection and integration, data screening and target verification in sequence. According to the invention, through multi-omics data integration and bioinformatics analysis, key driving genes of hepatocellular carcinoma are systematically screened, and the important effects of the genes in occurrence, development, metastasis, drug resistance and immune escape of hepatocellular carcinoma are disclosed; the genes not only deepen the understanding of the hepatocellular carcinoma molecular mechanism, but also provide important theoretical basis and potential intervention targets for the development of targeted therapy and personalized therapy strategies.

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen / LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

The invention discloses application of a palmitoylation inhibitor in prevention and treatment of gastric cancer. The chromatin remodeling protein SNF2 derived from S.anginosus EVs can be combined with a transcription factor TEAD1, so that the transcription of the palmitoyl transferase ZDHHC11 is promoted together. Then, the stability of the ZDHHC11 is enhanced by catalyzing palmitoylation of PD-L1, and finally immune escape is induced. In addition, SNF2 also can activate AXL, CTGF, CYR61 and other carcinogenic targets at the downstream of TEAD1, thereby further accelerating the malignant progression of gastric cancer. In an in-vivo experiment, the intragastric administration of the S.anginosus EVs not only promotes the tumor growth of mice, but also significantly inhibits the infiltration of CD8 + T cells. Blocking of ZDHHC11 can effectively reverse immune escape, and has a synergistic effect with an anti-PD-1 therapy, so that the treatment effect is remarkably improved.

The invention relates to the technical field of medical chemistry and tumor treatment, in particular to application of a novel NOX4 inhibitor ZZU026 and derivatives thereof in tumor resistance and immune response change. The preparation method of the ZZU026 comprises the following steps: replacing N, N-dimethylamino on a benzene ring of GKT137831 with morpholinyl; methoxyl is introduced into the core skeleton. The ZZU026 has a remarkable inhibiting effect on NOX4, has the functions of inhibiting tumor growth, new vascularization and immune-related diseases, regulating and controlling polarization of macrophages and the like, and can inhibit phenotype transformation of macrophages from M1 to M2 and finally inhibit proliferation and immune escape of lung cancer cells; the ZZU026 and the derivatives thereof can be prepared into drugs, health care products, tablets, particles, capsules, oral liquid or injection, and can be used for treating lung cancer and other tumors.

The invention relates to the technical field of biological medicines, in particular to a preparation method of an inhibitor targeting a MAX-PD-L1 promoter specific binding motif and a double-target inhibitor, through ChIP-seq and site-directed mutagenesis experiments, a core binding motif of MAX and a PD-L1 promoter, such as 5 '-CAC [GA] TG-3', is defined, it is ensured that the inhibitor only targets a key site of MAX-PD-L1 interaction, and the activity of the MAX-PD-L1 promoter specific binding motif is improved. The off-target effect is avoided, and a high-specificity target spot is provided for subsequent inhibitor design. The cell permeability of the DNA aptamer screened based on the specific binding motif is improved after cholesterol modification, and the affinity of the DNA aptamer is obviously higher than that of a traditional antibody. A small molecule compound virtually screened through a molecular docking model is optimized through hydrogen bond and hydrophobic interaction, and then the binding affinity with MAX is improved. After treatment with the inhibitor, the combination inhibition rate of MAX and the PD-L1 promoter is high, the transcriptional activity of PD-L1 is obviously reduced, the killing rate of T cells to tumor cells is also improved, and immune escape is effectively blocked.

Therapeutic agents that can place bulky proteins, such as CD45, CD148, and CD43, at the center of the cellular interface between graft cells and CD45-positive host effector cells (e.g., T cells, NK cells, B cells, or dendritic cells) are disclosed, as are methods of their use and products made with such therapeutic agents. The therapeutic agents prevent or inhibit the formation of functional immunological synapses (including physiological SMACs). They also result in the continuous dephosphorylation of signaling pathways.

The invention discloses an application of SNF2 protein derived from streptococcus angina extracellular vesicles in gastric cancer prognosis. The chromatin remodeling protein SNF2 derived from S.anginosus EVs can be combined with a transcription factor TEAD1, so that the transcription of the palmitoyl transferase ZDHHC11 is promoted together. Then, the stability of the ZDHHC11 is enhanced by catalyzing palmitoylation of PD-L1, and finally immune escape is induced. In addition, SNF2 also can activate AXL, CTGF, CYR61 and other carcinogenic targets at the downstream of TEAD1, thereby further accelerating the malignant progression of gastric cancer. In an in-vivo experiment, the intragastric administration of the S.anginosus EVs not only promotes the tumor growth of mice, but also significantly inhibits the infiltration of CD8 + T cells. Blocking of ZDHHC11 can effectively reverse immune escape, and has a synergistic effect with an anti-PD-1 therapy, so that the treatment effect is remarkably improved.

The application discloses a recombinant oncolytic virus targeting CD317 gene and application thereof in anti-tumor, and belongs to the technical field of tumor treatment. The recombinant oncolytic virus comprises a CD317 inhibitor and an oncolytic virus, and is formed by integrating the CD317 inhibitor into the oncolytic virus genome. The CD317 inhibitor is a substance capable of inhibiting CD317 gene expression or targeting degradation of CD317 protein function, and is selected from shRNA or siRNA targeting CD317. The application develops the oncolytic virus targeting knockdown of CD317 expression, inhibits tumor cell proliferation by reducing CD317 expression of tumor cells, reduces PD-L1 expression so as to break the immune escape mechanism, simultaneously enhances the killing sensitivity of tumor cells to CD8+ T cells, forms a synergistic effect with the oncolysis of the oncolytic virus, and the recombinant oncolytic virus has stronger in-vivo anti-tumor activity, thereby providing a new potential scheme for CD317-driven tumor treatment.

This invention provides an H3N2 influenza mRNA vaccine targeting the tandem HA and NA proteins and its preparation method, relating to the field of vaccine preparation technology. The H3N2 influenza mRNA vaccine is obtained by linking the conserved amino acid sequences of HA and NA of H3N2 with GGGSGGGSGGGSGGGS, and the amino acid sequence of the H3N2 influenza mRNA vaccine is shown in SEQ ID NO.1, and the nucleic acid sequence is shown in SEQ ID NO.2. This invention overcomes the shortcomings of existing technologies, improves the protective effect of the vaccine against H3N2 influenza, and enables it to better cope with immune evasion from the latest emerging H3N2 variants.

This application relates to the fields of chemistry and biomedicine, specifically to a tofenamic acid lipid composition, its preparation method, and its application. A tofenamic acid derivative is obtained by reacting a morpholine solution with tofenamic acid, ethyldimethylaminopropylcarbodiimide, and 4-dimethylaminopyridine, followed by purification. The morpholine in the morpholine solution is an N-alkylmorpholine compound. The tofenamic acid derivative is used to prepare tofenamic acid prodrug liposomes via ethanol injection, which are then used in combination with a STING agonist. The synergistic effect of the combined treatment stems from the dual regulation of the tumor immune microenvironment (TME), overcoming the immune escape induced by STING monotherapy. After STING agonist treatment, the intratumoral COX-2 / PGE2 axis is activated, leading to immunosuppression. The combination of tofenamic acid liposomes and a STING agonist inhibits COX-2, thus relieving this negative feedback loop.

The invention relates to miRNA, a miRNA simulant and a delivery system of the miRNA simulant, and belongs to the field of biological medicine. The sequence of the miRNA or the miRNA simulant is as shown in SEQ ID NO. 1. It is found for the first time that the miRNA or miRNA simulant can effectively inhibit immune escape and treat immunosuppressive cancers when being independently used as an active component. According to the invention, the miRNA or miRNA simulant is further combined with a photoresponsive plant exosome platform, so that the stability and delivery efficiency of the miRNA in a tumor microenvironment are improved, time-space precise release can be realized through light activation, and cancer cells and immunosuppressive cells driven by the cancer cells, such as M2 type macrophages, Treg and the like, can be effectively targeted. The strategy shows the comprehensive advantages of high efficiency, safety, controllability, personalized customization and the like, and has the potential of serving as a cancer therapeutic agent.

The invention relates to the technical field of biomedical detection, and discloses a system for detecting extracellular matrix free metalloproteinase and a soluble receptor. Comprising a polypeptide substrate nanopore sensing module used for detecting the enzyme activity of free metalloproteinase in an extracellular matrix; the electrophoretic analysis module is used for detecting a soluble receptor in an extracellular matrix, applying an electric field to a tumor microenvironment sample, determining the inter-terminal resistance of the sample by using an inter-terminal resistance detection device, and detecting the soluble receptor by comparing the resistance change according to the characteristic that the existence of the soluble receptor causes the additional resistance increase of the sample; and the data processing and judging module is electrically connected with the polypeptide substrate nanopore sensing module and the electrophoretic analysis module respectively, and is used for receiving the free metalloproteinase activity detection result and the soluble receptor detection result, and judging the time interval of cellular immune escape according to a preset rule in combination with cellular morphology observation information.

This invention provides the application of type IV collagen and its encoding gene in the prognostic assessment and treatment of nasopharyngeal carcinoma (NPC). Research has shown that high expression of type IV collagen and its encoding gene COL4A1 is significantly associated with lower T-cell infiltration in patients with recurrent NPC; compared to NPC patients with low expression of type IV collagen, those with high expression have worse LRRFS and OS; and the expression level of the type IV collagen encoding gene COL4A1 is significantly associated with worse PFS in NPC patients. Therefore, type IV collagen and its encoding gene COL4A1 can serve as specific prognostic biomarkers for assessing the prognosis of NPC patients. Furthermore, inhibiting the expression of type IV collagen can effectively inhibit the growth of NPC; therefore, agents that inhibit type IV collagen expression can be used as drugs to inhibit immune escape in NPC and for the treatment of NPC.

The invention belongs to the technical field of virus and gene engineering, and particularly relates to an expression vector of a respiratory syncytial virus (RSV) ON1 genotype consensus sequence strain and an editing strain, a reverse genetic manipulation system and an application of the reverse genetic manipulation system of the respiratory syncytial virus ON1 genotype consensus sequence strain and the editing strain of the RSV ON1 genotype consensus sequence strain and the editing strain of the respiratory syncytial virus ON1 genotype consensus sequence strain. According to the invention, an RSV-ON1 genotype consensus sequence strain is firstly constructed and saved, on the basis, 72 nucleotides which are repeatedly inserted into a G gene of the consensus sequence strain are removed through a gene editing technology, and two strains with different virus G gene sequences are obtained. According to the invention, through construction of RSV infectious clone edited by RSV-ON1 genotype G gene and rescue of the two strains, a fast, simple and accurate RSV reverse genetic system is constructed, and the RSV reverse genetic system can be applied to research on RSV in-vitro virus replication mechanism and pathogenesis and neutralizing antibody immune escape. A etiological technical platform is provided for research, development and evaluation of RSV vaccines, antibodies, drugs and the like.

The application discloses a kind of nanomaterial and its preparation method and application, the nanomaterial includes exosome and liposome;The exosome expresses immune checkpoint, the exosome is derived from brain glioma cell;The liposome is loaded with I type photosensitizer.The application is by PDT, immune checkpoint and brain glioma cell exosome antigen three tubes simultaneously to remodel tumor local immune microenvironment, greatly improve the efficiency of cancer immunotherapy, can activate strong anti brain glioma immune response and overcome immune escape.

This invention provides a biomarker for detecting immunotherapy resistance in gastric cancer, its application, a model, and a method for using it. This invention demonstrates the significant impact of the hypoxic tumor microenvironment on immunotherapy resistance in gastric cancer, highlighting the crucial roles of FOXO3a and PD-L1 expression in mediating immune escape mechanisms. By employing an innovative microfluidic tumor chip model, the in vivo hypoxic tumor environment was successfully simulated, revealing how hypoxia-induced upregulation of FOXO3a leads to enhanced PD-L1 expression, thereby resulting in immunotherapy resistance.

The invention relates to the field of biological medicine, and discloses a nano antibody aiming at DDR1, and a sequence and application thereof. The system disclosed by the invention reveals a DDR1-mediated immune escape network, and completes complete development work from a single-target antibody to a multifunctional fusion protein. The research and development of the DDR1nb-Fc and the derivative fusion protein DDR1nb-Fc-mCD80 of the DDR1nb-Fc and the derivative fusion protein DDR1nb-Fc-mCD80 of the DDR1nb-Fc provide a novel treatment strategy with high efficiency and safety for intractable tumors with abundant collagen matrixes.

The present application relates to the medical technical field, especially to the application of FYB1 gene as a marker in preparation of gastric cancer diagnosis or prognosis judging reagent. The present application research finds that FYB1 gene is highly expressed in gastric cancer tissue and negatively correlated with the prognosis of patients, and can be used as a gastric cancer marker for gastric cancer detection and efficacy evaluation. In addition, FYB1 is positively correlated with the expression of Treg cell marker FOXP3 and co-localized in tissues, suggesting that FYB1 may promote gastric cancer tumor immune escape; the expression of FYB1 gene can significantly inhibit the proliferation, migration and invasion ability of gastric cancer cells, and inhibit tumor growth, indicating that FYB1 gene can be used as a gastric cancer treatment target and play an important role in the treatment of gastric cancer patients.

The application discloses application of an MgdE gene in regulating virulence of Mycobacterium bovis, a nucleotide sequence of the MgdE gene is shown as SEQ ID NO. 1, an amino acid sequence of a coded protein is shown as SEQ ID NO. 2, the protein coded by the gene is a nuclear regulatory protein, depends on two nuclear localization signal peptides (NLS) to play a nuclear localization function, and then inhibits a host inflammation level, enhances survival and colonization of the bacteria in a host cell, the two NLS are respectively located at positions 108-111 and 300-305 of the amino acid sequence shown as SEQ ID NO. 2. The MgdE gene or the two NLS is modified to obtain a weak strain of Mycobacterium bovis, it is found for the first time that the MgdE gene and the two NLS can be used as important targets for inhibiting Mycobacterium bovis infection. The application has important application value in preparation of Mycobacterium bovis bacillus Calmette-Guerin (BCG), and also makes an important contribution to exploration of a pathogenic mechanism and an immune escape strategy of Mycobacterium bovis.

The present application provides a polypeptide or a pharmaceutically acceptable salt thereof, wherein the polypeptide has an amino acid sequence as shown in SEQ ID NO: 1. The polypeptide or the pharmaceutically acceptable salt thereof can bind to PD-1 and CTLA-4, and is used for effectively inhibiting PD-1 and CTLA-4. Thus, the polypeptide or the pharmaceutically acceptable salt thereof can be used for detecting PD-1 and / or CTLA-4, and can also be used for treating or preventing diseases mediated by PD-1 and / or CTLA-4 (such as tumors or cancers, for example, lung cancer, melanoma, lymphoma, leukemia and other diseases involving tumor immune escape).

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.

This invention discloses a bispecific nanobody targeting CXCL1 and PD-L1 and its applications, belonging to the fields of antibody engineering and bioengineering technology. The bispecific nanobody targeting CXCL1 and PD-L1 comprises at least one nanobody recognizing CXCL1 and one nanobody recognizing PD-L1, with the nanobody monomers linked by a linker. The bispecific nanobody targeting PD-L1 / CXCL1 provided by this invention has a unique structure, enabling it to specifically recognize and bind to both CXCL1 and PD-L1. It achieves an affinity of 1.08 nM for CXCL1 and 1.09 nM for PD-L1, effectively preventing immune escape-induced resistance to antibody therapy, making it suitable for a wider range of patients, and providing a new approach for CRC treatment.

The application discloses a recombinant FCV antigen and a construction method and application thereof. The construction method of the recombinant FCV antigen comprises the following steps: fusing a T cell epitope coding sequence of a non-structural protein NS7 of FCV and a coding sequence of a SpyTag peptide segment through a coding sequence of a linker, then cloning into a baculovirus transfer vector to obtain a recombinant plasmid, and finally integrating the T cell epitope coding sequence into Bacmid through Tn7 transposition to finally obtain the recombinant FCV antigen. The application selects NS7 as a core immunogen, guides the immune system to produce a high cellular immune response, and thus makes up for the deficiency of an existing vaccine in clearing intracellular viruses; meanwhile, a specific T cell epitope is selected in the sequence of NS7 as an immunogen, which can avoid the immunological escape caused by the variation degree of antigens among different strains and virus antigen drift, and thus provides broader protection.

This invention discloses a dual-targeting biomimetic liposome composite material, its preparation method, and its application, belonging to the field of nanomedicine technology. Using liposome nanoparticles as a carrier, evolocumab and shikonin are loaded onto the carrier to obtain drug-loaded liposomes. These drug-loaded liposomes are then fused with macrophage membranes and modified with phospholipid-modified hyaluronic acid to obtain the dual-targeting biomimetic liposome composite material. This invention utilizes evolocumab for lipid-lowering effects and shikonin for anti-inflammatory effects, employing two different mechanisms to achieve targeted therapy for atherosclerosis. The outermost biomimetic membrane leverages the inherent immune escape and recruitment characteristics of macrophages to achieve long-term blood circulation and targeted ability to lesion sites. By utilizing the interaction between hyaluronic acid and the CD44 receptor on the target cell surface, the composite material is effectively utilized by target cells, enhancing its efficacy in preventing and treating atherosclerosis.

The application of raspberry ketone in the immunotherapy of pancreatic cancer belongs to the technical field of biological medicine, and provides the application of raspberry ketone in the immunotherapy of pancreatic cancer. The application discloses that raspberry ketone can specifically and widely up-regulate the expression of MHC-I molecules on the surface of pancreatic cancer cells, and significantly enhances the infiltration and function of anti-tumor effector T cells in the tumor immune microenvironment. In-vivo and in-vitro experiments prove that raspberry ketone can reverse tumor immune escape by up-regulating MHC-I, and after being combined with a PD-1 immune checkpoint inhibitor, the raspberry ketone can produce a significant synergistic anti-tumor effect, significantly inhibit the growth of pancreatic cancer and prolong the survival period of tumor-bearing mice. The application provides a new strategy of combining a natural small molecule immunomodulator with an existing immunotherapy, and provides an innovative solution and a drug candidate for overcoming the difficulty of pancreatic cancer tolerance to immunotherapy.

The invention belongs to the field of biological medicine, particularly relates to application of a VIRMA inhibitor in preparation of a medicine for treating colorectal cancer, and finds that the expression level of VIRMA in the colorectal cancer is remarkably increased and is closely related to poor prognosis. Further experiments prove that the VIRMA can significantly enhance the proliferation and migration ability of colorectal cancer cells, accelerate the progress of a cell cycle and inhibit cell apoptosis. Meanwhile, m6A modification is carried out on RNA (Ribonucleic Acid) of STING by VIRMA under mediation of YTHDF2 so as to reduce the stability of STING mRNA (Messenger Ribonucleic Acid), so that malignant progression and immune escape of colorectal cancer are promoted.