35 results about "Dc vaccine" patented technology

The invention provides an applicable population screening method and application of a glioma dry-like cell sensitized DC vaccine, peripheral blood of a patient before and after inoculation of the glioma dry-like cell sensitized DC vaccine is obtained, mononuclear cells are extracted, CD8 + T cells are respectively separated from the mononuclear cells through a magnetic bead sorting method, and the CD8 + T cells are separated from the mononuclear cells. The method comprises the following steps: uniformly inoculating CD8 < + > T cells into an ELISPOT cell culture plate coated with an IFN-gamma antibody for culture, respectively setting an experimental group and a positive control group for culture, adding A2B5 < + > glioma cell lysis buffer into the experimental group and adding phytohemagglutinin into the positive control group, and carrying out ELISPOT staining on the cultured cells to obtain the secretion amount of FN-gamma before and after treatment of a patient. According to the secretion amount of the FN-gamma, patients with specific immune response to the glioma dry-like cell sensitization DC vaccine are screened, so that the glioma dry-like cell sensitization DC vaccine is conveniently popularized and applied, and the immune mechanism of the glioma dry-like cell sensitization DC vaccine is researched.

Disclosed are modified DAP12 and methods of their use for enhancing immune responses and for treating cancer.

The present disclosure belongs to the field of biotechnology, and specifically relates to a preparation method for an adenovirus p53 (Ad-p53)-loaded dendritic cell (DC) vaccine. The present disclosure includes steps of peripheral blood collection and peripheral blood mononuclear cell (PBMC) separation, PBMC sorting, DC activation, Ad-P53-transfected DC and DC vaccine preparation. P53 can be expressed on a surface of DC as a tumor-associated antigen (TAA) through DC purification, specific multiplicity of infection (MOI) and infection modes, and the Ad-P53-transfected DC has obvious antigen presentation effect, which can be used as a vaccine to activate T cells to kill tumors.

The invention discloses a preparation method and application of a dendritic cell vaccine. The preparation method of the dendritic cell vaccine comprises the following steps: designing a new antigen mRNA sequence; preparing virus-like particles containing annular mRNA according to a new antigen mRNA sequence; dC is transfected through virus-like particles containing annular mRNA, and the DC vaccine of the tumor new antigen is obtained. The DC vaccine of the annular mRNA can be individually designed and prepared according to an amino acid sequence or a nucleotide sequence of a tumor neoantigen, accurate application of different individuals is realized, the stability of the annular mRNA in cells is higher, the annular mRNA can be directly expressed in the cells, and antigen information is more efficiently ingested and presented by the DC.

The invention discloses a novel immune enhancement system, which comprises a specific TLR4 agonistic polypeptide and a CD40 single-domain antibody. According to the polypeptide, a KLAKLAK core module is adopted, penetrating peptide and hydrophobic groups are modified, and an NF-kappa B / MAPK pathway can be effectively activated; the antibody is obtained through shark immune screening and has high affinity to CD40. When in combined application, the GM-CSF / IL-4-containing medium synergistically promotes the maturation of dendritic cells, so that the expression of CD80 / CD86 / MHC-II is improved by more than 2 times, the secretion amount of IL-12 reaches 165 pg / mL, and the proliferation rate of T cells is improved to 48.6%. Animal experiments show that the T cell stimulation index of a combined group reaches 6.2, and the serum IFN-gamma level is improved by 9 times. The composition provided by the invention can significantly enhance the DC vaccine efficacy, and has important application value in the field of tumor immunotherapy.

The invention discloses a preparation and delivery strategy of a dendritic cell targeting vaccine. The vaccine delivery platform comprises: a) an antibody having a DC targeting function, which is selected from a targeting antibody of CD205; and b) a carrier antigen which is obtained by fusion expression of the antibody affinity molecule integrated with the non-natural amino acid and the antigen epitope or the antigen epitope splicing protein. According to the present invention, the CD205 antibody is adopted, the antigen epitope fusion protein containing the antibody affinity molecule is prepared through the UAA integration technology, and the fusion protein can be subjected to proximity induction coupling with the CD205 antibody through the UAA affinity molecule so as to achieve the efficient self-assembly of the CD205 and the antigen epitope; the vaccine delivery platform provided by the invention can realize accurate, efficient and switchable antigen delivery, provides a simple, convenient and flexible DC vaccine design strategy suitable for different antigens, and has a wide immunotherapy application prospect.

The invention provides a dendritic cell vaccine for treating bone and soft tissue sarcoma as well as a preparation method and application of the dendritic cell vaccine. The dendritic cell vaccine comprises mature dendritic cells obtained by co-culturing sarcoma cell lysate and immature dendritic cells. The lysates of seven sarcoma cells are used as dendritic cell vaccine antigens, the problem that an existing DC vaccine is single in loaded antigen is solved, antigen presentation and T cell activation are enhanced, wide immune response is excited, immune escape is reduced, and the dendritic cell vaccine is not limited by the type of MHC of a patient, is high in universality and can benefit more patients.

The application belongs to the field of biological pharmacy, and particularly relates to application of a Caerin polypeptide combined with a dendritic cell vaccine in preparation of a drug for treating breast cancer. The application finds that F1 / F3 significantly inhibits proliferation of 4T-1 cells and induces cell death in vitro, significantly inhibits growth of a primary tumor, reduces lung metastasis, and prolongs overall survival in vivo, and inoculation of a DC vaccine loaded with a tumor-related antigen can reduce tumor growth and enhance T cell activation in draining and non-draining lymph nodes. Compared with a vaccine loaded with a whole antigen (DCV1), a DC vaccine (DCV2) combined with F1 / F3 induced 'programmed death antigen' exhibits stronger anti-tumor activity, although TNF-alpha and IL-12 secretion thereof is lower. Therefore, the application combines the F1 / F3 polypeptide with the DCV2 to prepare a drug for treating breast cancer, effectively improves the treatment effect on the tumor, and highlights the importance of a combined immunotherapy strategy.

The invention discloses a method for preparing a dendritic cell vaccine through in-vitro amplification and induction of hematopoietic stem cells, and belongs to the field of biomedicine.The amplification induction method specifically comprises the following steps that firstly, peripheral blood is collected, the collected peripheral blood is diluted, and then peripheral blood mononuclear cells are separated; according to the invention, the conditions that cells enter an inflammatory emergency state due to a large dose of IL-4 in a traditional scheme, metabolic routes such as cell glycolysis are highly activated, ROS release is caused by oxidative stress, and cell dysfunction is caused by abnormal metabolism are avoided, and a cell combination closest to real DC cell phenotype and function in a human body can be obtained; the antigen presentation of the DC vaccine is improved to the maximum extent, meanwhile, hematopoietic stem cells can be partially differentiated to a myeloid system, DC progenitor cells and DC precursor cells, effective amplification of dozens of times can be achieved in quantity, and the technical bottleneck that the clinical curative effect is limited due to insufficient cell quantity is solved.

The invention provides a microvesicle-loaded DC vaccine as well as a preparation method and application thereof, DC is taken as a carrier, microvesicles are loaded, and the DC-loaded microvesicles are derived from hepatoma carcinoma cells Hepa1-6; the preparation method comprises the following steps: (1) culturing liver cancer Hepa1-6 cells, exposing the cells in an ultraviolet environment for irradiation, then collecting cell supernatant, and extracting MPs; (2) obtaining bone marrow single cells, firstly inducing the bone marrow single cells into imDC (imDC), and then inducing the bone marrow single cells into mature DC (mDC); and (3) incubating the DC and the MPs to obtain the DC vaccine loaded by the microvesicles. The invention also discloses an application of the DC vaccine loaded by the microvesicles in preparation of drugs or preparations for treating liver cancer. The DC vaccine loaded by the microvesicles can promote the activation of CD8 + T cells and the killing ability to liver cancer cells. According to the present invention, the liver cancer cells can be specifically killed without damaging other tissues, the specific recognition and killing function of the T cells on the tumor cells can be enhanced, and the tumor immune escape can be easily overcome.

The invention belongs to the technical field of nano biomedicine, and particularly discloses a preparation method of a galangin-loaded bionic nano dendritic cell (DCs) vaccine and application of the galangin-loaded bionic nano dendritic cell (DCs) vaccine in ovarian cancer treatment. The inner core of the vaccine is galangin (GA)-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles, and the shell of the vaccine is formed by coating a DCs film carrying tumor antigens. The nano DC vaccine retains the antigen presentation function of natural DCs, and the GA loaded on the nano DC vaccine can induce tumor cells to generate immunogenic cell death. By means of the design, the vaccine can efficiently load specific tumor-associated antigens, and the homing capacity of the vaccine to lymph nodes and tumor microenvironments is remarkably enhanced. Experiments show that GA-NPs (at) DCV is used for treating subcutaneous tumor and in-situ ovarian cancer mouse models.

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 invention relates to the field of biological pharmacy, in particular to a DC vaccine, drug-loaded nanoparticles and a preparation method and application of the DC vaccine and the drug-loaded nanoparticles. The composition provided by the invention comprises 0.1 to 50 mM of a cellular pathway inhibitor, mOVA-loaded LNPs containing a tumor antigen, and 0.01 to 50 [mu] g / mL of a cellular pathway agonist. According to the construction and preparation method of the DC vaccine and drug-loaded PLGA nano-particle co-delivery system, the DC vaccine is combined with the agonist-loaded PLGA nano-particles for use, so that T cells are effectively and specifically activated, and an efficient anti-tumor effect is achieved. The combination mode obviously improves the tumor inhibition effect, and the effect is better than that of separate use.

The invention relates to the technical field of biological medicines, in particular to a dendritic cell vaccine for multiple myeloma as well as a preparation method and application of the dendritic cell vaccine, and the dendritic cell vaccine is obtained by co-culturing dendritic cell vaccines MOLP-8, RPMI-8226, NCI-H929, U266B1 and MM1. S whole cell line lysates and dendritic cells. According to the present invention, the whole cell line lysates of MOLP-8, RPMI-8226, NCI-H929, U266B1 and MM1. S are adopted as the antigen of the DC vaccine, and the mixed lysates contain rich tumor antigens, can activate the immune system, and can generate the cytotoxic T cells aiming at the multiple myeloma antigens so as to specifically kill the tumor cells. The DC vaccine prepared by the invention not only stimulates T cells to generate more IFN-gamma, but also induces to generate stronger tumor killing T cells, and provides a new thought for research and development of multiple myeloma DC vaccines.

The invention discloses a DC vaccine and application of the DC vaccine and NKG2D-CAR-T cells combined with the DC vaccine in preparation of drugs for treating tumors and drugs for enhancing the curative effect of the CAR-T cells. According to the combined immunotherapy method for enhancing the curative effect of the CAR-T cells and the application of the combined immunotherapy method, the CAR-T cells are prepared from the NKG2D-CAR expressed on the T cells, the CAR-T cells and the DC vaccine loaded with the tumor antigen RAE1 are co-cultured, the killing and multiplication capacity of the NKG2D-CAR-T cells, the secretion and activation level of cell effector factors and the like are studied, and the CAR-T cells and the DC vaccine loaded with the tumor antigen RAE1 are used for enhancing the curative effect of the CAR-T cells. Therefore, the influence of the DC vaccine on the anti-tumor aspect of the NKG2D-CAR-T cells is evaluated. The invention further provides an osteosarcoma animal model, preparation thereof and application of the osteosarcoma animal model in an in-vivo experiment in which the DC vaccine is combined with NKG2D-CAR-T cells to remarkably improve the tumor killing capacity. The invention also discloses a DC vaccine which can obviously improve the tumor killing ability of NKG2D-CAR-T cells, the activation and proliferation level is obviously improved, and in-vivo research finds that the survival rate of mice is obviously improved, and a very good tumor growth inhibition effect is achieved.

Provided herein are methods and materials for treating cancer (e.g., ovarian cancer) using Th17 DC vaccines, optionally in combination with immune checkpoint inhibitors.

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 belongs to the field of biological pharmacy, and particularly relates to application of a Cererin polypeptide combined dendritic cell vaccine in preparation of a medicine for treating breast cancer. It is found that F1 / F3 significantly inhibits proliferation of 4T-1 cells in vitro, induces cell death, significantly inhibits growth of primary tumors in vivo, reduces lung metastasis and prolongs the overall lifetime, and inoculation of a DC vaccine loaded with tumor-associated antigens can reduce tumor growth and enhance T cell activation in drainage and non-drainage lymph nodes. Compared with a vaccine (DCV1) loaded with a holoantigen, the DC vaccine (DCV2) combined with a programmed death antigen induced by F1 / F3 shows higher anti-tumor activity, although the secretion of TNF-alpha and IL-12 is lower. Therefore, the F1 / F3 polypeptide and the DCV2 are combined to prepare the medicine for treating the breast cancer, the tumor treatment effect is effectively improved, and the importance of a combined immunotherapy strategy is highlighted.

The application belongs to the technical field of biological medicine, and specifically discloses a method for applying induced pluripotent stem cell-derived exosomes in a DC vaccine. The application provides a preparation method of a tumor vaccine, which comprises the following steps: using induced pluripotent stem cell exosomes to sensitize DC cells to obtain the tumor vaccine. The induced pluripotent stem cell-derived exosomes provided by the application have the characteristics of uniform particle size, low toxicity, good cell compatibility, high yield and the like. The DC vaccine provided by the application has the abilities of tumor treatment, tumor prevention and tumor metastasis inhibition, and has low toxicity, and is a simple, practical and applicable technology and method. The application solves the problems of tumorigenicity, large volume, interception by lung and other tissues, difficulty in being taken up by DC, only tumor prevention ability and the like of the existing induced pluripotent stem cell vaccine, and solves the problem of lack of antigen source in the construction of the DC vaccine.

The present invention discloses the application of Glycyrrhiza inflata polysaccharide in the preparation of drugs for treating and / or preventing liver cancer, belonging to the technical field of vaccine adjuvants. The crude Glycyrrhiza inflata polysaccharide GiP and the homogeneous Glycyrrhiza inflata polysaccharide GiP-B1 provided by the present invention have relatively significant antitumor activities when acting synergistically with dendritic cells (DCs). At the same time, the crude Glycyrrhiza inflata polysaccharide GiP and the homogeneous Glycyrrhiza inflata polysaccharide GiP-B1 can also promote the maturation of the phenotype of bone marrow-derived DCs in normal mice and improve the antigen presentation function of DCs. The DC vaccine loaded with tumor antigen prepared by the present invention can promote the maturation of DCs, up-regulate the expression of surface marker molecules of DCs, and has a certain immunotherapeutic effect on H22 liver cancer-bearing mice. The Glycyrrhiza inflata polysaccharide can be used as a DC vaccine adjuvant for the preparation of drugs for treating and / or preventing liver cancer.

The invention discloses a nano tumor DC vaccine for simulating dendritic cells as well as a preparation method and application of the nano tumor DC vaccine, belongs to the technical field of biological medicines, and discloses a novel nano tumor DC vaccine for simulating dendritic cells, which is formed by ultrasonic fusion of an engineered DC cell membrane and ferrous folate nanoparticles. The DC cell membrane is extracted, and a key molecular structure on the DC cell membrane is reserved as a vaccine main body, so that the risk of a living cell vaccine can be greatly reduced; the FFNP not only can be used as an immunologic adjuvant to increase the number of CD8 + T cells in a tumor immune microenvironment, but also can be used as a DC cell membrane filler to enlarge the surface area of the DC cell membrane and maintain better trafficability of the sphere-like structure of the vaccine. According to the present invention, the molecular biology, the material science and the bioinformatics are adopted to determine that the Hybrid DC has DC antigen presentation, lymph node homing and killing T cell activation capacities, can improve the tumor immune microenvironment, and can reverse the immunosuppression phenomenon;

The present invention discloses an adjuvant for enhancing the efficacy of dendritic cell vaccines and its application, belonging to the field of biotechnology. The present invention discloses an adjuvant AOAA for enhancing the efficacy of dendritic cell vaccines, which can significantly enhance the immunogenicity of DCs, upregulate the expression of proinflammatory factors IL-6, IL-12, IL-23, TNFα and co-stimulatory molecules CD80 and CD86 in DCs, and promote DC-mediated CD4 + T cells and CD8 + The ability of T cells to differentiate into IFNγ-secreting effector T cells; moreover, AOAA can be used in the preparation of DC vaccines to enhance the anti-tumor effect of DC vaccines.

The present invention discloses the tumor immunotherapy use and preparation method of NRTUA-DC obtained by stimulating DCs with non-toxic Toxoplasma gondii (NRTUA). The present invention discovers for the first time that the NRTUA-DC vaccine obtained in vitro by activating isolated mouse dendritic cells (DCs) with non-replicating uracil auxotrophic atoxic Toxoplasma gondii (NRTUA) is significantly effective in treating CT-26 mouse colorectal cancer. This overcomes the limitation of conventional dendritic cell (DC) vaccines in terms of poor anti-tumor therapeutic effect, provides a stimulator that better activates the antigen presentation ability of DCs, and reveals its anti-tumor immunoregulatory effect.

The invention relates to the technical field of biological medicines, in particular to a method for screening a high-activity dendritic cell vaccine by utilizing CD39 and TIM3, which comprises the step of sorting and / or identifying mature dendritic cells by utilizing biomarkers CD39 and TIM3. According to the invention, CD39 and TIM3 are taken as biomarkers for sorting the mo-DC, the high-activity mo-DC vaccine can be screened out, and experimental results show that the high expression of the biomarkers such as CD11C, HLA-DR and CD197 in the mo-DC vaccine obtained by the method is realized; meanwhile, the experimental result also shows that the T cell proliferation proportion of the CD39 + TIM3 + DC stimulation group is obviously higher than that of the DC stimulation group, which indicates that the DC sorted by the CD39 and TIM3 has strong immune response induction capability and is obviously higher than that of the un-screened moDC-DC group.

The invention discloses a preparation method of a traditional Chinese medicine polysaccharide assisted pancreatic cancer DC vaccine. The preparation method comprises the following steps: extracting mouse bone marrow dendritic cells; the preparation method comprises the following steps: cracking and centrifuging mouse bone marrow dendritic cells through a red blood cell lysis solution, cleaning a culture medium, and culturing in a special culture medium to obtain immature dendritic cells; collecting the PANC2 pancreatic cancer cells subjected to amplification culture, counting, putting into a cryopreservation tube, and preparing a tumor antigen by a low-temperature and normal-temperature repeated freezing and thawing method; the preparation method comprises the following steps: co-culturing immature dendritic cells and tumor antigen for 12-24 hours, adding traditional Chinese medicine polysaccharide, continuously culturing until the dendritic cells are mature, and re-suspending the co-cultured cells in normal saline to obtain the pancreatic cancer DC vaccine. The prepared traditional Chinese medicine polysaccharide assisted pancreatic cancer DC vaccine has the advantages of high maturity, enhanced phenotypic signal molecule expression and the like, and can effectively inhibit tumor cell growth when being independently applied to a pancreatic cancer tumor-bearing mouse model.

The present application relates to the technical field of biomedicine, and relates to the preparation of a dendritic cell vaccine for pancreatic cancer and the use thereof in the preparation of a drug for treating pancreatic cancer. The preparation method comprises the preparation of Panc-1 and AsPC-1 lysates, the preparation of immature dendritic cells, and the preparation of a DC vaccine loaded with the Panc-1 and AsPC-1 lysates.

The present application relates to the technical field of biological medicine, and more particularly to a method for screening high-activity dendritic cell vaccine by using CD39 and TIM3, which comprises the steps of sorting and / or identifying mature dendritic cells by using biomarkers CD39 and TIM3. The present application takes CD39 and TIM3 as biomarkers for sorting mo-DC, and can screen high-activity mo-DC vaccine. Experimental results show that the mo-DC vaccine obtained by using the method has high expression of biomarkers such as CD11C, HLA-DR and CD197. Meanwhile, the experimental results also show that the T cell proliferation ratio of the CD39+TIM3+DC stimulation group is significantly higher than that of the DC stimulation group, indicating that the DC sorted by using CD39 and TIM3 has strong ability to induce immune response, and is significantly higher than the mo-DC group without screening.

The present application relates to a kind of renal cancer therapeutic DC vaccine based on the immune peptide activation of HERV-E protein source and its preparation method, and the preparation method includes the following steps: obtaining immature DC cell;Synthesis HERV-E protein source immune peptide;Immune peptide and immature DC are co-cultured in DC activation culture medium for 1 day to DC maturation.The renal cancer therapeutic DC vaccine obtained by the way of immature DC loaded with HERV-E immune peptide is more stable in character, and has strong anti-tumor capacity, can effectively inhibit the progress of renal cancer.

The present application belongs to the field of medical immunology, and particularly relates to a polypeptide composition specifically binding to HLA-A2 typing and application, the polypeptide composition is selected from one or more polypeptides derived from antigen proteins Survivin, Her2, CEA, hTERT, MAGE-A3, EGFR, gp100 or p53, the polypeptide derived from each antigen protein contains an antigen epitope or a variant of the antigen epitope of each antigen protein.The polypeptide composition is presented and activates specific CD8+ cytotoxic T lymphocytes by loading antigen presenting cells to achieve the targeted toxicity effect on tumor cells.The polypeptide composition of the present application and the tumor vaccine, DC vaccine, pharmaceutical composition derived therefrom can significantly activate immune effector cells, especially T cells, significantly improve the secretion level of the activated related cytokines and the killing level on tumor cells, and have potential clinical value.