139 results about "Immune escape" patented technology

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 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.

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 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.

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 discloses a targeted protein degradation nano-vesicle as well as a preparation method and application thereof. The nano-vesicle comprises a shell and a targeted chimera wrapped in the shell, the shell is formed by fusing cell membranes and lipidosome; the shell carries a PD-1 protein and a targeting molecule. The targeted protein degradation nanovesicle provided by the invention can penetrate through a blood brain barrier to enter the intracranial, CAR protein specifically targets ligands on the surfaces of glioma cells, PD-1 protein interacts with mPD-L1 on the surfaces of the glioma to inhibit immune escape, PROTAC molecules efficiently degrade endogenous cPD-L1 of the glioma cells, and precise and efficient immunotherapy of the glioma is achieved.

The invention provides a polypeptide or a pharmaceutically acceptable salt thereof. The polypeptide has an amino acid sequence as shown in SEQ ID NO: 1. The polypeptide or the pharmaceutically acceptable salt of the polypeptide can be combined with PD-1 and CTLA-4, and is used for effectively inhibiting the PD-1 and the CTLA-4. Therefore, 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 PD-1 and / or CTLA-4 mediated diseases (such as tumors or cancers, such as lung cancer, melanoma, lymphoma, leukemia and other diseases related to tumor immune escape).

The invention provides a polypeptide for inhibiting tumor immune escape and application thereof. The polypeptide is a peptide derived from 181-190 amino acids at the amino terminal of ubiquitin specific protease 15 (USP15), enters tumor cells by means of a cell-penetrating peptide CPP, and can obviously block the combination of USP15 and PD-L1 in the tumor cells, promote ubiquitination degradation of PD-L1, obviously lower the level of tumor cells PD-L1, inhibit tumor immune escape and play an in-vitro and in-vivo anti-tumor role. In addition, when the U10 polypeptide and the PD-1 monoclonal antibody (mAb) are jointly applied to a mouse body, the effect of synergistically resisting tumor immune escape is achieved. Therefore, the U10 polypeptide can be used as a new strategy of immune checkpoint blocking treatment, is used for tumor immunotherapy, and has important clinical application value.

The invention belongs to the technical field of biological medicine, and particularly relates to application of UFL1 gene in preparation of a product for regulating and controlling tumor immune escape. The invention provides an application of a UFL1 gene in preparation of a product for regulating and controlling tumor immune escape. A nucleotide sequence of the UFL1 gene is shown as SEQ ID NO. 1; the tumors include pancreatic cancer. By taking UFL1 as a target spot and knocking out the UFL1 gene, the quality and volume of pancreatic cancer can be inhibited, and the proportion of CD8 + T cells and the level of immune cell factors can be improved; the proportion of immunosuppression Treg, MDSCs and M2 type macrophages is reduced, and the tumor immune microenvironment is regulated and controlled, so that the immune escape of the tumor is inhibited.

The invention discloses a bionic hybrid carrier for actively targeting hypertrophic scars as well as a preparation method and application of the bionic hybrid carrier. According to the preparation method, materials such as scar fibroblast cell membrane protein, a cation carrier and siRNA are adopted, hybridization of a cell membrane and the cation carrier is achieved through an ultrasonic co-extrusion technology, and the carrier is endowed with immune escape and homologous targeting capacity; high-efficiency loading of TGF-beta1 siRNA is realized by utilizing electrostatic self-assembly, so that a bionic transdermal delivery system with an active targeting characteristic is constructed. The bionic hybrid carrier not only provides an innovative thought for root therapy of hypertrophic scars, but also opens up a new way for gene intervention of other skin fibrosis and inflammation related diseases, and has important clinical transformation value.

The invention discloses a CAR-T drug resistance marker, a CAR-T drug resistance mediating preparation composition and application thereof, and relates to the technical field of biological medicine, the technical key points are as follows: the marker is FADD protein and OR10J1 protein, an activator targeting the downstream of FADD or an activator targeting the downstream of OR10J1 is combined with CAR-T, and the CAR-T drug resistance mediating preparation composition can be prepared into a drug-resistant drug-resistant drug. According to the present invention, the mutation of the FADD signal channel or the OR10J1 signal channel can be eliminated, the tumor immune escape caused by the mutation of the FADD signal channel or the OR10J1 signal channel can be overcome, the new strategy is provided for the CAR-T treatment to overcome the liver cancer immune escape, the strategy can be used for the escape of other types of the immune-killed tumors by using the channel, and the new idea is provided for the treatment of the drug resistance or the recurrence caused by the CAR-T treatment.

This invention discloses a near-infrared cyclic metallic iridium (III) photosensitizer and its synthesis method. The BDP-Ir prepared by the method of this invention can be used at low doses (IC50). 50 =68nM) at low power (10mW·cm) ‑2 It exhibits high photosensitivity under 808nm excitation, successfully solving the problem of sacrificing both excitation wavelength and photosensitivity efficiency; at the same time, its synergistic biomimetic artificial nano-hybrid delivery system can effectively enhance the tumor targeting and immune escape ability of photosensitizers.

The invention discloses application of a targeted Nup85 inhibitor in preparation of a medicine for preventing or treating hepatocellular carcinoma, and relates to the technical field of biological medicine and tumor immunotherapy. The invention provides an application of a targeted Nup85 inhibitor in preparation of a medicine for preventing or treating hepatocellular carcinoma. The inhibitor prevents and / or treats hepatocellular carcinoma by enhancing CD8 + T cell functions, enhancement of the CD8 + T cell functions is realized by regulating STAT1 / CCL5 / CXCL10 pathways, and Nup85 reduces expression of CCL5 and CXCL10 by inhibiting nuclear translocation of phosphorylated STAT1, so that infiltration and activation of CD8 + T cells are inhibited. The invention discloses an immune escape mechanism that Nup85 inhibits CD8 + T cell infiltration by inhibiting p-STAT1 nuclear translocation and down-regulating CCL5 / CXCL10 expression in liver cancer for the first time, provides a new liver cancer immunotherapy target, and broadens the application of nucleopore protein in tumor immunotherapy; the target Nup85 inhibitor can be obtained through a conventional means, a new clinical application direction of the target Nup85 inhibitor is defined, and the target Nup85 inhibitor has good clinical transformation and development prospects.