116 results about "Immune microenvironment" patented technology

Measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9), which determination may be referred to herein as a two gene score (TGS), powerfully predicts overall survival in patients with NHL, particularly overall survival in the context of anthracycline-based chemotherapy or co-treatment with anthracycline-based chemotherapy and anti-CD20 immunotherapy. It is shown herein that increased levels of LMO2 and TNFRSF9 correlate with a positive patient response and improved prognosis.

The invention relates to a CAR-T cell specifically targeting CD19 antigen and stably expressing PD-1 antibodies at high levels as well as an application of the CAR-T cell. Specifically, the T cell ofthe invention contains and expresses a coding sequence of a CAR (chimeric antigen receptor) recognizing CD19 antigen and a coding sequence of the PD-1 antibodies; and / or expresses the CAR recognizingCD19 antigen and the PD-1 antibodies. The T cell can overcome immune microenvironment suppression, promotes apoptosis of tumor cells, develops an anti-tumor immune response, and can be applied to treatment of multiple types of malignant tumors.

The invention relates to CAR-T cells with specifically targeted Muc1 antigens capable of stably expressing PD-1 antibodies at high levels, as well as usage thereof. Specifically, the CAR-T cells provided by the invention have a coding sequence of a chimeric antigen receptor expressing and recognizing Muc1 antigens and a coding sequence of PD1 antibodies; and / or the CAR-T cells comprise chimeric antigen receptors expressing and recognizing the Muc1 antigens, as well as PD-1 antibodies. The chimeric antigen receptors provided by the invention sequentially comprise, from N-terminals to C-terminals, membrane protein signal peptides, anti-Muc1 membrane proximal single-chain antibodies, hinge regions of which the lengths are 50 amino acid residues or above, transmembrane regions, intracellular domains of costimulatory signaling molecules and immunoreceptor tyrosine-based activation motifs. The CAR-T cells provided by the invention are capable of overcoming inhibition of immune micro-environment, promoting apoptosis of tumor cells, and exerting anti-tumor immune response; and thus, the CAR-T cells provided by the invention can be used for treating a multiple kinds of Muc1-positive malignant tumors.

The invention provides a culture and cryopreservation method for a prostatic cancer organoid with a tumor immune microenvironment. The culture and cryopreservation method comprises the following steps: separating mononuclear cells and autoserum from peripheral blood, and stimulating the mononuclear cells by using a CD28 antibody and IL-2; separating tumor cells from a prostatic cancer tissue sample; mixing the tumor cells with a culture medium and a temperature-sensitive hydrogel, and then carrying out culturing and subculturing to obtain a tumor organoid precursor; stimulating the tumor organoid precursor by using IFN-gamma, and then conducting dissociating to form stimulated tumor cells; mixing the stimulated tumor cells with the stimulated mononuclear cells, conducting stimulating witha PD-1 antibody, mixing the stimulated mixture with the temperature-sensitive hydrogel, and carrying out culturing; and cryopreserving the tumor organoid with a cryopreservation solution containing FBS and the temperature-sensitive hydrogel. With the method in the invention, the success rate of culturing of organoids with a tumor microenvironment can be greatly improved at low cost.

The invention provides a PD-1 gene silenced CD133-targeting CAR T cell and application thereof. The PD-1 gene silenced CD133-targeting CAR T cell is characterized in that a preparation method thereofcomprises the following steps: firstly importing CRISPR-Cas9 and a transposon system into PBMC by using a nucleofection system, activating a T cell, and conducting T cell expansion to obtain the PD-1gene silenced CD133-targeting CAR T cell. The PD-1 gene silenced CD133-targeting CAR T cell provided by the invention can solve PD-1 pathway mediated immunosuppression and prevent tumor metastasis andrecurrence. In comparison with PD-1 or PD-L1 antibody combination therapy, the PD-1 gene silenced CD133-targeting CAR T cell can effectively avoid systemic toxicity problems and accurately regulate the immune microenvironment.

The invention discloses an application of bee venom lipid nanoparticles, which relates to the technical field of biological science and a pharmaceutical carrier. The bee venom lipid nanoparticles of the invention are composed of bee venom hybrid polypeptide and phospholipid and cholersteryl ester. The immune activation and anticancer agent prepared by the bee venom lipid nanoparticles is used fortargeting antigen presenting cells, and activates antigen presenting cells to improve the immune microenvironment, so as to generate a systemic immune response and inhibit tumor growth and metastasiseffect; the agent is also used to target and activate dendritic cells, macrophages, and B cells to inhibit the production of distant tumors; and the agent is also used to target hepatic sinusoidal endothelial cells and induce them to release a variety of immune factors to inhibit tumor liver metastasis. The immune activation and anticancer agent prepared by the bee venom lipid nanoparticle has notoxic and side effects, does not depend on the tumor type, and has good anti-tumor effect.

The invention discloses a scoring method for quantifying a TIME infiltration mode; the score for quantifying the TIME infiltration mode is called as a TIME index (TI), the TI is an excellent prognosisprediction index in hepatocellular carcinoma and pancreas carcinoma, and the performance of the TI in predicting immunotherapy response is superior to that of other 11 biomarkers. The results can strengthen the understanding of the immune microenvironment and guide more effective personalized treatment, and the TIME1 is characterized by immune cell depletion and cell proliferation and correspondsto immunodeficiency types; tIME2 is characterized by being in an immunosuppression state, and a potential immune escape mechanism of each phenotype is emphasized corresponding to immunosuppression: TIME1 is characterized by tumor infiltration leukocyte deficiency and tumor antigen presentation capability defects; the TIME2 has more immunosuppressive cells; the TIME3 is rich in immunosuppressive cytokines and immune checkpoint molecules.

The invention discloses repair spray containing high-concentration human mesenchymal stem cell extracts for a small pet and a preparation method of the repair spray. The repair spray mainly comprises the high-concentration mesenchymal stem cell extracts. Mesenchymal stem cells can secrete various cell factors in the culture process, the cell factors can penetrate into an endomembrane base layer, endomembrane tissue differentiation, vessel regeneration and granulation tissue growth are promoted, injured skin tissue structure regeneration and repair are promoted, generation of scar connective tissues is decreased, a skin immune microenvironment is regulated, and bacterial infection and inflammatory reaction of wound tissues are decreased. By a continuous mesenchymal stem cell starving method, high-concentration human umbilical cord mesenchymal extracts can be obtained in a short time. The repair spray containing the high-concentration mesenchymal stem cell extracts is applicable to repair of eczema, chronic surface ulcers and various skin injuries.

The invention belongs to the field of medicine and relates to application of a CD73 ADC and particularly relates to application of the CD73 ADC in preparation of a drug which can kill high-expressiontumor cells in CD73- and activate a tumor immune microenvironment by inhibiting a CD73 adenosinase pathway. Compared with the prior art, the application verifies unique double technical effects of theCD73-ADC, wherein on one side, the CD73 ADC can directly kill the high-expression tumor cells in the CD73- and on the other side, the CD73 ADC activates the immune microenvironment by inhibiting theCD73 adenosinase pathway; and the dual-overlaid pharmacological mechanism is characterized by being efficient and low-toxicity and providing a new strategy for treatment of refractory tumors.

The invention belongs to the field of tissue engineering, and particularly relates to a bionic degradable artificial nerve conduit for regulating and controlling immune microenvironment and guiding regeneration by utilizing a topological structure. The bionic degradable artificial nerve conduit comprises a shell (1) and inner fibers (2), wherein the shell (1) adopts a first material with degradation time of 12-24 months; and the inner fibers (2) are made of a second material with the degradation time of 3-10 months. The bionic degradable artificial nerve conduit has the beneficial effects thatthe macrophages can be regulated and controlled by the internal fibers, so the macrophages are polarized into M2 phenotypes for promoting tissue regeneration, and nerve regeneration is further promoted; the degradation speed of the shell is matched with a nerve scar formation period, so infiltration of surrounding tissue is effectively prevented, and formation of scar tissue is avoided; and the shell is provided with pores, so nutrient exchange and substance transfer of nerve cells in the regeneration process are not influenced.

The invention provides an efficient and low-toxin tumor therapeutic agent and a preparation method and application thereof, and particularly provides IL-12 / CD62L fusion protein. Anti-tumor T cells are modified through slow viruses containing IL-12 / CD62L fusion genes, and by means of specific cleavage and release induced by activation of CD62L tumor antigen dependence, release of cell membrane surface IL-12 activated through tumor antigens is achieved. A is shown through experiments, fixed-point and timed release of IL-12 can be achieved locally on tumors attacked by the T cells, so that the immune microenvironment of T cell-tumor tissue is changed, and accordingly the anti-tumor immune effect is the maximum. Besides, the toxic and side effects are remarkably reduced.

The invention provides an M1 type macrophage exosome vaccine as well as a preparation method and application thereof. The M1 type macrophage exosome vaccine is characterized in that an exosome vaccine M1Ag-Exos is obtained by enabling M1 type macrophages to uptake a specific tumor antigen Ag and then extracting an exosome of the M1 type macrophages carrying the tumor antigen Ag. According to the M1 type macrophage exosome vaccine, the exosome vaccine capable of adjusting the tumor immune microenvironment is constructed to enhance the immunotherapy efficiency, and polarization of tumor-related macrophages and the remarkable immune activation effect of a tumor vaccine are achieved through the M1 type macrophage exosome; the tumor-related macrophages are polarized into M1 type, so that the macrophages are converted from a state of promoting tumor invasion and metastasis by immunosuppression into a state of supporting tumors by immunity; meanwhile, through immunoregulation on the tumor microenvironment, the tumor vaccine can promote proliferation and activation of T cells more efficiently, and growth and metastasis of the tumors are effectively inhibited.

The invention discloses an application of a proteasome inhibitor in anti-cancer drugs. The proteasome inhibitor comprises Carfilzomib (carfilzomib), Bortezomib (bortezomib), MLN9708 (ixazomib), MG132and the like. The targeted cancer is a cancer in which macrophage polarization participates, i.e., a tumor in which the macrophage type is mainly M2 type in a tumor microenvironment, including a solidtumor and a hematologic tumor, and also including an in-situ cancer and a transplanted cancer. It is found through a large amount of creative work that the proteasome inhibitor converts M2 type TAM in the tumor immune microenvironment into M1 type TAM, thereby improving the tumor microenvironment, promoting the phagocytic effect of macrophages on tumor cells and increasing infiltration of immunecells on tumors to inhibit tumor growth.

The invention provides a hypoxia-related gene marker combination for hepatocellular carcinoma and application thereof. A hypoxia score obtained by using the hypoxia-related gene marker combination can better reflect the hypoxia exposure condition of hepatocellular carcinoma tissues, and the hepatocellular carcinoma is subjected to typing and prognosis analysis. Meanwhile, the hypoxia-related gene marker combination is used for comprehensively exploring the change of hypoxia-related molecular markers in the hepatocellular carcinoma from multiple aspects of genomics, epigenomics, transcriptomics, proteomics and the like, a more complete hepatocellular carcinoma hypoxia-related molecular landscape is described, meanwhile, the immune microenvironment change of liver cancer is analyzed, and more valuable information is provided for diagnosis and treatment of the hepatocellular carcinoma.

The invention belongs to the field of clinical medicine, and relates to a model for predicting the curative effect of hepatocellular carcinoma immunotherapy based on 5 genes and a construction method thereof. The model for predicting the immunotherapy effect of hepatocellular carcinoma comprises five genes, namely lactic dehydrogenase A (LDHA), phosphatide phosphoramidate heterogeneous enzyme (PPAT), a bead fiber structural protein 1 (BFSP1), a nuclear receptor sub-fiber 0 group B member 1 (NR0B1) and 6-phosphatide-2-kinase / fructolase-2,6-diphosphatase 4 (PFPFB4). The invention also provides a construction method of the model for predicting the curative effect of hepatocellular carcinoma immunotherapy based on the 5 genes. Herein, the new immune microenvironment model based on 5 genes is established, so that the effect of a patient on HCC immunotherapy can be effectively predicted, and the 5 genes can be used as potential biomarkers to be clinically applied.

The present invention discloses an anti-TLP2 antibody. Said anti-TLR2 antibody can inhibit tumor, specially can inhibit the metastasis of B16 melanin tumor. Said anti-TLR2 antibody not only can block TLR2 activity, but also can obviously reduce number of metastatic foci of lung. At the same time, said invention finds that the bleomycin and said anti-TLR2 antibody have good synergistic action.

The invention discloses a construction method of a tumor immune microenvironment prediction model based on RNAseq. The method comprises the first step of determining 24 cell types related to the tumormicroenvironment; the second step of selecting 301 marker genes preferably according to the cell types obtained according to the above step; the third step of calculating the gene expression amount TPM using kallisto software, calculating the average expression amount of a corresponding marker gene of each cell type and then taking a log value as the relative abundance of the cell type. Accordingto the construction method, the average expression amount of the corresponding marker gene of each cell type is calculated, that is, the average value of a set of marker genes, and the result is relatively more stable and less affected by the relative error compared with calculation of the single marker gene.

The present invention provides a CAR-T cell self-expressing a PD-1 immunological checkpoint inhibitory antibody and targeting a chimeric antigen receptor of ErbB receptor family and a use thereof. TheT cell comprises a coding sequence expressing the chimeric antigen receptor targeting the ErbB receptor family and a coding sequence of the PD1 antibody; and / or expressing the chimeric antigen receptor targeting the ErbB receptor family and the PD1 antibody. The T cell has better proliferation and activation ability than those of a T cell singly targeting the chimeric antigen receptor of the ErbBreceptor family, can overcome inhibition of an immune microenvironment, promotes apoptosis of tumor cells, and exerts an anti-tumor immune response and a tumor cell killing function.

The invention discloses an immune cell containing a tumor antigen recognition receptor and application of the immune cell. The immune cell containing the tumor antigen recognition receptor expresses hyaluronidase, wherein the hyaluronidase comprises: a) a full-length protein anchored to the immune cell; or b) a soluble protein secreted to the outside of the immune cell. The invention also discloses application of the immune cell in preparation of drugs for treating tumors. According to the immune cell containing the tumor antigen recognition receptor, an effect of normalizing a tumor immune microenvironment by changing the extracellular matrix structure of the microenvironment can be changed, so that the immune cell can effectively approach and kill tumor cells. With the help of the soluble PH20 protein, the immune cell containing the tumor antigen recognition receptor can also improve the tumor microenvironment and effectively kill the tumor cells.

The invention relates to the technical field of bio-medicine, in particular to application of PINK1 serving as a diagnostic marker in construction of a lung squamous cell carcinoma prognosis prediction model. The biomarker PINK1 and other clinical indexes are used in a combined mode, and lung squamous cell carcinoma prognosis detection can be assisted. According to the invention, screening and construction are carried out after full transcriptome sequencing and machine learning of a lung squamous cell carcinoma specimen based on large-sample anti-tumor immuno-therapy, so that the prognosis condition of a lung squamous cell carcinoma patient can be efficiently and accurately predicted; and meanwhile, according to the correlation between the risk and different immune cell infiltration levels, immune-related pathways, key immune checkpoint inhibitor expression levels and the like, comprehensive evaluation of the tumor immune micro-environment is achieved, effective guidance is provided for clinicians to make a treatment decision on lung squamous cell carcinoma patients, invalid treatment is reduced, and therefore, the treatment cost and discomfort experience of the patients are reduced.

The invention discloses application of SFRP4 as a gastric cancer prognosis marker, belongs to the field of tumor molecular biology, and further discloses application of the SFRP4 as a treatment target in preparation of gastric cancer treatment drugs, expression up-regulation of the SFRP4 in gastric cancer tissues is remarkably related to poor prognosis; the SFRP4 is obviously related to abundance of various lymphocytes, immunomodulators and chemotactic factors in gastric cancer tissues, so that the survival time of a patient can be better predicted, even the state of an immune microenvironment can be evaluated, and the SFRP4 is a potential useful and reliable biomarker for guiding immunotherapy and determining prognosis of the gastric cancer patient. The invention also provides an application of the SFRP4 combined with CD8 + T as a gastric cancer prognosis marker, the gastric cancer prognosis can be better predicted by combining the SFRP4 combined with the CD8 + T, and the good prognosis of a patient is prompted by the low expression of the SFRP4 and the high infiltration of CD8 + T cells in a tissue sample.

The invention relates to the technical field of anti-tumor treatment drugs, in particular to application of beta-glucan combined with an anti-tumor drug in anti-tumor treatment. Beta-glucan is beta-glucan polysaccharide derived from yeast and comprises beta-1,3 / 1,6 glucan, and structurally, a yeast beta-glucan main chain is formed by connecting glucose monomers through beta-(1, 3) bonds, and a side chain is connected to the main chain by glucose through a beta-(1, 6) glycosidic bond; and beta-glucan and an antibody or a small molecule drug are applied in a combined mode, the anti-tumor effectis achieved by improving the tumor immune microenvironment, beta-glucan can promote natural immune effector cells to kill complement-conditioned tumor cells through a complement CR3 dependence mechanism, and multiple animal tumor models show that compared with any monotherapy, the situation that the beta-glucan and a complement activator or an anti-tumor antibody are combined for treatment can remarkably delay the tumor growth, and the total lifetime can be prolonged.

The invention discloses fibrin gel containing adriamycin-entrapped platelet exosome and PD-L1 monoclonal antibody as well as a preparation method and application thereof, and belongs to the technical field of medicines, and compared with an adriamycin solution, the adriamycin-entrapped platelet exosome can be better combined with tumor cells, induce death of immunogenic tumor cells and promote anti-tumor immune response. Meanwhile, the blood platelet exosome loaded with adriamycin can enter blood circulation through damaged blood vessels, and tumor cells in circulation are tracked and removed. The aPD-L1 is released at the tumor site at the same time, so that a PD-1 / PD-L1 pathway can be blocked, and the tumor killing effect of cytotoxic T cells is recovered. The combination of the two strategies can trigger stronger T cell immune response, and obviously improves the tumor immune microenvironment. The method provided by the invention provides a new strategy and more choices for the combination of chemotherapy and immunotherapy, and meets the urgent demand on efficient preparations in clinic.

The invention relates to the technical field of biomedicine, in particular to an EGFP-Wnt2 fusion protein antigen, a Wnt2 monoclonal antibody and an application of a Wnt2 monoclonal antibody. The EGFP-Wnt2 fusion protein antigen is mainly a fusion protein of EGFP and a full-length amino acid sequence of a humanized Wnt2 signal-erasing peptide. The EGFP-Wnt2 fusion protein antigen comprises an EGFPamino acid sequence, a TEV restriction enzyme cutting site and a FLAG tag sequence, and the Wnt2 signal-erasing peptide full-length amino acid sequence, a 6* His tag sequence and an anti-Wnt2 monoclonal antibody can be used for inhibiting immune escape and growth of tumor cells. When the Wnt2 monoclonal antibody disclosed by the invention is combined with the human Wnt2 antigen secreted by cells,the promotion of the cell on the formation of an inhibitory immune microenvironment in a tumor is antagonized, and the immune escape and growth of the tumor cell are inhibited. The Wnt2 monoclonal antibody provided by the invention can be used in immune treatment of solid tumors such as esophageal squamous carcinoma, gastric cancer, pancreatic cancer, colorectal colon cancer, lung cancer, breastcancer, glioma, liver cancer and the like.

The present invention provides liposomes co-carrying CD73 antibody and doxorubicin and its preparation method and application, wherein, the liposomes co-carrying CD73 antibody and doxorubicin is a lipid core coated with doxorubicin, The CD73 antibody is modified outside the lipid core, and the CD73 antibody is modified on the surface of the lipid core by coupling to the phospholipid PEG active ester micelles. The liposomes co-carrying CD73 antibody and doxorubicin provided by the invention reduce the drug resistance and side effects of doxorubicin in the treatment of triple-negative breast cancer, improve the biodistribution of doxorubicin in the body, and increase the bioavailability , and reversed the immune microenvironment in the tumor of triple-negative breast cancer, turning it into a hot tumor, and achieved a better therapeutic effect on triple-negative breast cancer.

The invention provides a method for reconstructing a colorectal cancer organoid immune microenvironment. The method comprises the following steps: constructing a colorectal cancer organoid by using fresh colorectal cancer tissue; obtaining peripheral blood, then performing erythrocyte lysis, and separating lymphocytes by adopting a lymphocyte separating medium; enriching CD3 <+> T cells; and digesting the organoids into single cells, co-culturing the single cells and the cultured CD3 <+> T cells according to a ratio of 1: (10-30), and constructing the colorectal cancer patient-derived organoids immune microenvironment according to the steps. According to the method for reconstructing the colorectal cancer organoid immune microenvironment provided by the invention, fresh colorectal cancer tissue from the same individual and CD3 <+> T cells from peripheral blood are co-cultured to obtain the organoid immune microenvironment, it is, from cellular morphology and ATP values, shown that immune cells have an obvious killing effect on organoids of CRC patients, and an in-vitro experimental basis is provided for immunotherapy of clinical autologous T cell transfusion.

The invention relates to a pharmaceutical composition for tumor immunotherapy, and provides a new application of radionuclide or a marker thereof, and the new application is an application of the radionuclide or the marker thereof in remodeling a tumor immunological microenvironment. The invention also provides a pharmaceutical composition for tumor immunotherapy of a human body or a mouse. The pharmaceutical composition is prepared from radionuclide or the marker thereof and an immune checkpoint inhibitor according to a specific ratio. The invention also provides a kit for tumor immunotherapy. The kit contains the pharmaceutical composition for tumor immunotherapy of human bodies or mice. According to the pharmaceutical composition provided by the invention, the tumor immune microenvironment can be remodeled while the tumor is detected through radionuclide or the marker thereof, so that the tumor growth speed is remarkably reduced through the immune checkpoint inhibitor, and the lifetime is prolonged. The pharmaceutical composition disclosed by the invention has a good synergistic effect, and the kit disclosed by the invention is convenient to use and easy to realize clinical popularization.

The invention belongs to the technical field of genetic engineering and biomedical engineering, and particularly discloses a mesenchymal stem cell preparation used for glioma immunotherapy and meanwhile capable of realizing magnetic resonance tracing. The mesenchymal stem cell preparation comprises mesenchymal stem cells capable of simultaneously secreting interferon-beta (IFN beta) and realizingmagnetic resonance (MR) imaging. The mesenchymal stem cells are jointly modified with IFN beta and FerritinH genes, can adjust the tumor immune microenvironment by secreting an immunomodulatory factorIFN beta, and exerts an inhibition effect on glioma growth; and meanwhile, through FerritinH reporter gene magnetic resonance (MR) imaging, the stem cells after transplanting are monitored dynamically, non-invasively and systematically in real time at the living body level, the experimental basis is provided for promoting stem cell therapy clinical transformation, a new means is provided for deeply illuminating the stem cell action mechanism, and the important scientific significance and clinical application prospects are achieved in aspects of stem cell therapy and transgenic therapy of glioma.

The invention belongs to the field of biological medicines, and relates to a dual-modified engineered bacterium and application thereof, in particular to an engineered bacterium externally coupled with an immune checkpoint inhibitor and internally coded with a tyrosinase gene, a pharmaceutical composition containing the dual-modified engineered bacterium and application of the pharmaceutical composition. Wherein the engineered bacterium is preferably escherichia coli. By utilizing the engineered bacteria, melanin expression and distribution which are controllable in space and time are obtained, melanin is similar to an inhibitor in distribution, and the melanin and the inhibitor are combined to enhance a dual-immune activation effect and synergistically reprogram a tumor immune microenvironment. The engineered bacterium can significantly inhibit tumor growth and prolong the lifetime by being singly used or combined with a conventional tumor treatment mode or medicine. The pharmaceutical composition containing the bacteria or the application of the pharmaceutical composition not only overcomes the difficult tumor inner barrier, but also has good permeability, and can uniformly and enduringly disperse the anti-tumor drug into the whole tumor.

The invention relates to the technical field of medical biology, in particular to a tumor combined treatment preparation with a cell exosome loaded excitation reagent and a photosensitizer and application thereof. The tumor combined treatment preparation is a carrier for loading an excitation reagent, a photosensitizer and a biological reducing drug in a glial cell exosome differentiated space, and the excitation reagent can excite the photosensitizer to react and emit light and is used for replacing laser; the biological reducing drug is loaded on glial cell exosomes and is used for penetrating deep tissues to perform immune microenvironment regulation and control. The tumor combined treatment preparation has no toxic or side effect on normal tissues, can penetrate through the blood-brain barrier (BBB), is small in drug resistance and cannot cause tumor cell metastasis.