93 results about "CD86" patented technology

The invention is applicable to the technical field of biological pharmacy, and provides application of a novel nano drug-loading delivery system of exosome-loaded ginsenoside Rh2. The ginsenoside Rh2 and the MSC-derived exosome are subjected to blending ultrasonic treatment to realize exosome drug loading, and a novel Rh2-coated MSC-exo nano drug loading delivery system is synthesized. Animal experiments show that the Rh2 (at) MSC-exo novel nano drug-loading delivery system can be targeted to ectopic intimal lesions and has an inhibition effect; the expression level of an M1 type macrophage marker CD86 is enhanced, and the expression level of an M2 type macrophage marker CD206 is inhibited; the m6A level and the METTL3 expression level of ectopic endometrial tissues are reduced; according to the present invention, RNA-seq and MIP-seq sequencing is adopted to determine that WNT2 is the potential target of the Rh2 (at) MSC-exo novel nanometer drug loading delivery system affecting ectopic inner membrane m6A modification;

The invention relates to the technical field of cellular immunotherapy, in particular to application of efonidipine in preparation of a dendritic cell immunologic adjuvant. The invention provides an application of efonidipine in preparation of a dendritic cell immunologic adjuvant. It is found that efonidipine can promote maturation, migration and antigen presentation functions of DCs, and the homing ability of DCs and CD8 + T cell activation are remarkably improved. The activation aspect of efonidipine on DCs comprises improvement of expression of maturation indexes CD80, CD40 and CD86, expression of a migration index CCR7, activation of CD8 + T cells by antigen presentation and the like. The efonidipine used in the invention is a drug approved by FDA for clinical treatment of cardiovascular diseases, the application of the efonidipine in immunotherapy is found, new use of old drugs is realized, and the efonidipine has great economic value.

This invention relates to CTLA-4 protein compositions and their use in the mitigation of autoimmune adverse events associated with cancer immunotherapy.

The invention provides a construction method and application of a gene modified K562 cell line, and belongs to the technical field of biological medicines. According to the invention, two viruses CD86-4-1BBL and mbIL-21 are respectively subjected to gene transduction packaging by adopting a third-generation lentivirus four-plasmid packaging system, a K562 cell line is infected by the lentiviruses CD86-4-1BBL and mbIL-21, and a monoclonal cell line capable of stably expressing CD86, 4-1BBL and mbIL-21 proteins is obtained through screening. According to the method, cell lines with the cloning numbers of V5-E9, V10-A5, V5-D6 and V6-D7 are obtained through screening, the four cloning cell lines can serve as feeder cells for stimulating NK cell amplification after being amplified and subjected to irradiation treatment, NK cell amplification can be effectively promoted, the amplification multiple of the NK cells reaches up to 6000-8000, and large-scale preparation and production of the NK cells for treatment are met.

The invention belongs to the technical field of nanogel preparations, and particularly relates to application of nanogel to preparation of anti-tumor drugs or preparation of the anti-tumor drugs. Experiments find that nanogel with proper hardness can promote expression of M1 related proteins CD86 and iNOS, and up-regulate expression of CD86 mRNA and iNOS mRNA, so that M2 type tumor related macrophages are reversely polarized into M1 type tumor related macrophages. Further research finds that after the nanogel is used for carrying out reverse polarization treatment on M2 type tumor-related macrophages, tumor cell proliferation can be inhibited, tumor cell apoptosis can be induced, and tumor cell phagocytosis can be realized. In addition, the nanogel with proper hardness is directly delivered into the tumor in an intratumor injection manner, so that the growth of the tumor can be effectively inhibited.

The invention relates to the field of cell biology, and particularly relates to a preparation method of a pancreatic cancer-related antigen-loaded polypeptide, which is characterized in that factors such as GM-CSF, IL-4, IFN-gamma, TNF-alpha, IL-1beta, IL-6, PGE2, Poly I: C, R848 and the like are added to promote mononuclear cells to be activated into DC cells, pancreatic cancer PANC-1, MIA PaCa-2, BxPC-3, KP4 and SW1990HM antigens are loaded, and not only is DC cell maturation promoted, but also pancreatic cancer-related antigens are loaded. The positive rate of CD83 + CD86 of the DC cells cultured by the method is 94.16%, and the secretion amount of IL-12p70 in a cell supernatant is (645.38 + / -36.49) pg / mL. By adopting the culture method disclosed by the invention, the maturation rate of the DC cells can be improved while the DC cells are activated, so that the culture method for promoting the maturation and amplification of the DC cells loaded with the pancreatic cancer antigen is achieved.

The invention relates to a fusion polypeptide and application thereof, and particularly, the fusion polypeptide comprises a part capable of blocking a PD-1 / PD-L1 signal, CD86 or a functional active fragment thereof and / or a part capable of activating an immune response. The invention also provides application of the polypeptide.

To provide variant CD86 polypeptides, immunomodulatory proteins comprising variant CD86 polypeptides, and nucleic acids encoding the proteins, having therapeutic utility for a variety of immunological and oncological conditions.SOLUTION: Provided is a variant CD86 polypeptide, comprising an extracellular domain or an IgV domain or specific binding fragment thereof, the variant CD86 polypeptide comprising one or more amino acid modifications among specific amino acid sequences.SELECTED DRAWING: Figure 24A

The invention discloses an immunologic adjuvant containing paris polyphylla glucomannan for the first time, and belongs to the technical field of biological medicines. The immunologic adjuvant containing the paris polyphylla glucomannan can promote the phagocytic function of macrophages, promote the secretion of NO and TNF-alpha, promote the maturation of dendritic cells, up-regulate the expression quantity of CD40, CD86 and MHCII, and promote the secretion of TNF-alpha, IL-6 and IL-12. In-vivo experiments show that the immunologic adjuvant containing the paris polyphylla glucomannan can significantly improve the antigen-specific IgG, IgG1 and IgG2a antibody levels, induce Th1 and Th2 type immune responses at the same time, increase the proportion of CD3 + and CD3 + and CD4 + cells in splenic lymphocytes and enhance humoral immunity and cellular immunity levels at the same time. The paris polyphylla gulcomannan in the immunologic adjuvant is obtained by extracting and purifying paris polyphylla plants of alaginaceae, the weight-average molecular weight of the paris polyphylla gulcomannan is 50-800 kDa, monosaccharide composition of the paris polyphylla gulcomannan is mannose and glucose, the ratio of the mannose to the glucose is (10: 1)-(20: 1), and the second site or the third site of the mannose is substituted by acetyl. The invention further discloses a preparation method of the immunologic adjuvant containing the paris polyphylla glucomannan and application of the immunologic adjuvant containing the paris polyphylla glucomannan to preparation of a vaccine preparation or a vaccine composition.

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.

To provide an allogeneic tumor cell vaccine.SOLUTION: Provided is an allogeneic tumor cell vaccine, comprising: (1) a population of proliferation-incompetent, live, genetically engineered tumor cells expressing one or more tumor-specific antigens, the population comprising at least three stably expressed immunomodulatory molecules, at least three immunomodulatory molecules being OX40 ligand (OX40L), CD27 ligand (CD70), and CD28 ligand (CD28L) including CD80, CD86, or both, to induce one or more subpopulations of PBMCs to proliferate in response to the expressed immunomodulatory molecules and subsequently enter an effector phase to kill tumor cells, and the subpopulations of PBMC cells comprising one or more of T lymphocytes, natural killer (NK) cells, dendritic cells (DCs), or B lymphocytes; and (2) a pharmaceutically acceptable carrier.SELECTED DRAWING: None

The invention belongs to the technical field of vaccines, and particularly relates to a manganese-based platelet carrier vaccine based on a biomimetic mineralization technology and application of the manganese-based platelet carrier vaccine in immunotherapy. A manganese-based shell is deposited on the surface of a platelet, immunocompetence molecules such as CD40L and PF4 are expressed on the surface of the platelet, dendritic cells (DC) can be activated by directly contacting or secreting cell factors, and antigen presentation is promoted; in addition, deposited manganese ions can activate a cGAS-STING pathway, and meanwhile, CD40 / CD80 / CD86 / MHC-II costimulatory molecular expression on the surface of the DC is up-regulated. The vaccine adjuvant provided by the invention can be used for loading an antigen to form a three-in-one vaccine complex of the antigen (loaded on a platelet membrane), the platelet and a manganese shell, so that not only is the natural targeting capability of the platelet retained, but also DC cross presentation is enhanced through continuous release of manganese ions, finally CD8 + T cells are synergistically activated to react with an antibody, and the immune response of the antigen is enhanced. The antiviral immune response of the body is enhanced.

The invention relates to the field of biological medicine, in particular to a lipidosome hybridized nano-vesicle vaccine loaded with piperazosin, a preparation method of the lipidosome hybridized nano-vesicle vaccine and application of the lipidosome hybridized nano-vesicle vaccine in preparation of anti-tumor drugs. The lipidosome hybrid nano-vesicle vaccine loaded with the prazosin, disclosed by the invention, can be used for inhibiting autophagy and inducing the death of immunogenic cells of tumors. The pirazosin-loaded liposome hybrid nano-vesicle vaccine can activate and promote the maturation of bone marrow-derived dendritic cells, the expression of costimulatory factors CD80 and CD86 is obviously increased, and the antigen presentation is better promoted. The lipidosome hybrid nano-vesicle vaccine loaded with the prazosin can promote infiltration of mature dendritic cells and T cells in tumor tissues, can remarkably inhibit tumor growth, can remodel a tumor microenvironment as a tumor vaccine, and effectively improves the immunotherapy effect.

The invention relates to a method for detecting an immune state in thymus hyperplasia tissue in an EB (Epstein-Barr) virus infection state, which comprises the following steps of: constructing a kit comprising a quantum dot coupled CD19 antibody and a quantum dot coupled CD86 antibody; after the conjugate of the quantum dot and the specific antibody is specifically combined with an antigen on a B cell in a tissue slice sample, marking of the quantum dot on a costimulatory molecule on the surface of the B cell is realized; and judging the immune state of the thymus hyperplasia tissue according to a marking result. The quantum dot coupling antibody can be directly combined with an antigen on a tissue slice to realize direct marking of the quantum dot coupling antibody on the tissue slice, so that the B cell surface costimulatory molecules in a thymus hyperplasia tissue microenvironment are quantified and positioned, the relationship between the B cell surface costimulatory molecules and thymus hyperplasia-related autoimmune diseases is determined, and the accuracy and the sensitivity of the B cell surface costimulatory molecules in the thymus hyperplasia tissue microenvironment are improved. The immune state of the thymus hyperplasia tissue microenvironment can be evaluated, and autoimmune diseases can be predicted.

The invention relates to the technical field of cellular immunotherapy, in particular to application of drafenib mesylate in preparation of a dendritic cell (DCs) immunologic adjuvant. The invention provides an application of drafenib mesylate in preparation of a dendritic cell immunologic adjuvant. It is found that darfenib mesylate can promote the maturation and migration functions of DCs, and the migration ability of DCs is remarkably improved. The DCs activation aspect of the darfenib mesylate comprises improvement of expression of maturation indexes CD80, CD40 and CD86 and expression of a migration index CCR7. Darrafenib mesylate used in the invention is a chemotherapeutic drug approved by FDA for clinical treatment of patients with BRAF V600 mutation positive non-resectable or metastatic melanoma, the application of Darrafenib mesylate in immunotherapy is discovered, new use of old drugs is realized, and the Darrafenib mesylate has significant economic value.

Provided herein are particles comprising a fusion molecule comprising an adhesion molecule linked to a co-stimulatory molecule or an activating molecule; the present invention relates to fusion molecules, as well as vectors such as lentiviral vectors comprising the fusion molecules, cells comprising the fusion molecules, and methods of using the fusion molecules. The particle may be a lentiviral particle that displays a fusion molecule on a surface of the particle, the fusion molecule comprising: a) a CD58 extracellular domain or a functional fragment thereof, b) an antigen-binding fragment of an anti-CD3 antibody, and c) a CD80 or CD86 extracellular domain or a functional fragment thereof; and a viral glycoprotein (G protein).

The invention relates to the technical field of biology, and discloses a kit for predicting clinical pregnancy outcome of first-time frozen embryo transplantation. The kit comprises immune cells and immune factors in blood, the immune cells comprise CD19 < + > B cells, CD3 < + > T cells, CD4 < + > Th cells, CD8 < + > Ts cells, CD4 < + > / CD8 < + > ratio cells, CD56 < + > NK cells, CD68 < + > monocytes, CD86 < + > M1 sample monocytes, D206 < + > M2 sample monocytes and CD163 < + > M2 sample monocytes; the immune factors comprise IL-1beta, IL-2r, IL-6, IL-8 and TNF (Tumor Necrosis Factor)-alpha. According to the application, the importance of the peripheral blood CD163 + M2 sample mononuclear cell on predicting the continuous pregnancy of first embryo implantation of an FE T patient is confirmed, and the peripheral blood CD163 + M2 sample mononuclear cell is prompted to be possibly a biomarker of an FET period.

The invention discloses a polypeptide with tumor cell killing activity. The specific molecular target or the fusion polypeptide thereof is co-cultured with autoimmune cells of a subject, and then the autoimmune cells are transfused back into the body of the subject, so that targeted killing of tumor cells is realized, and the purpose of treating tumors is achieved. The dendritic cell (DC) load positive rate activated by the molecular target is greater than 90%. Furthermore, the activated DC cells highly express CD80 and CD86 on the surface, and can effectively present tumor antigens to T lymphocytes, thereby inducing to generate CTL cells with the capability of specifically recognizing cancer cells.

The invention relates to application of beta-glucan in preparation of a preparation for reducing the expression quantity of related genes of skin extracellular matrix inflammation. The structure of the beta-glucan is formed by connecting structural units. The invention also provides a biomarker, the biomarker is a gene related to skin extracellular matrix inflammation, and the gene comprises any one or a combination of at least two of IL1A, IL1B, IL1R1, IL1RAP, IL6, NFKB2, FOSB, FOSL1, JUN, JUND, CCL2, PTGS2, MMP10, MMP12, MMP13, CXCL8, CD86, PLAU, GADD45A, TNFSF18, TNFRSF10B, TNFRSF12A, TNFRSF14 or TNFRSF21.

The application discloses an antigen-engineered nanovesicle vaccine (AN-FV) and a preparation method and application thereof. The vaccine is formed by fusion of vesicles of tumor cell membranes obtained by pretreatment of functionalized nanometer preparations and vesicles of mature dendritic cell membranes; the functionalized nanometer preparations contain autophagy inhibiting siRNA and an immunogenicity enhancer, and can synergistically improve MHC-I expression of tumor cells and antigen immunogenicity. The vaccine of the application simultaneously presents high-density MHC-I-antigen peptide complexes and CD80 / CD86 costimulatory molecules on the surface of a single particle, simulates an immune synapse in a nanometer scale, and thus efficiently activates tumor-specific T cells. The vaccine integrates antigen source engineering, physiologicalization of costimulatory signals and nanometer platform integration, and provides a new scheme for overcoming the treatment bottleneck of immune "cold" tumors such as pancreatic cancer.

This document provides methods and materials involved in assessing immune system profiles. For example, methods and materials for performing flow cytometry to determine the number of CD4+ lymphocytes, CD8+ lymphocytes, regulatory T cells, B cells, NK cells, granulocytes, CD14+HLA-DRlo / neg monocytes, and / or CD86+ monocytes per unit volume (e.g., cells per μL or mL) of whole blood (e.g., fresh, un-manipulated whole blood) obtained from a mammal (e.g., a human) are provided.

The invention belongs to the technical field of biological medicines, and particularly relates to application of crizotinib in induction of tolerant dendritic cells (tDCs). The invention provides an application of crizotinib in induction of tolerant dendritic cells. It is found that crizotinib can serve as an efficient inducer of tDCs, the activation state of DCs can be remarkably inhibited, the maturation function of DCs can be inhibited, the immune stimulation capacity of DCs can be reduced, then activation of T cells is inhibited, and therefore the crizotinib plays a role in treating immune diseases such as GVHD. In the invention, the inhibition of crizotinib on DCs comprises reduction of expression of maturation indexes CD80, CD40 and CD86. The crizotinib used in the invention is an ALK / ROS1 inhibitor approved by FDA and is mainly used for treating non-small cell lung cancer, the application of the crizotinib in immunotherapy is found, new use of old medicines is realized, and the crizotinib has great economic value.

The invention provides a tumor-associated fibroblast targeting nano adjuvant as well as a preparation method and application thereof, and belongs to the field of nano drugs. The nano adjuvant (named as PF9PEI and alpha PC NPs) provided by the invention is coupled with PEI25K modified by 3-perfluorobutyl-1, 2-epoxypropane by utilizing a PD-L2 targeting peptide nrirgenyryh, so that an efficient gene vector (PF9PEI) is formed, and is used for loading an alpha PD-L1-P2A-CD86 plasmid. According to the nano adjuvant, CAFs can be reprogrammed into engineered antigen presentation CAFs by expressing a costimulatory molecule CD86, so that T cell immunity of breast cancer specificity is activated, and T cell failure is retarded at the same time. Besides, the engineered CAFs generated by the nano adjuvant generate alphaPD-L1 locally, so that the immune escape mechanism of breast cancer cells is effectively blocked, and the immune surveillance function of T cells is recovered. After radiotherapy, by using the nano adjuvant for treatment, the generation of central memory T cells is promoted, the progress of the same solid tumor is inhibited, the tumor metastasis is eliminated, and the tumor recurrence is inhibited.

Various cells, stem cells, and stem cell components, including associated methods of generating and using such cells are provided. In one aspect, for example, an isolated cell that is capable of self-renewal and culture expansion and is obtained from a subepithelial layer of a mammalian umbilical cord tissue. Such an isolated cell expresses at least three cell markers selected from CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105, and does not express at least three cell markers selected from CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR.