536 results about "Immune checkpoint" patented technology

The invention provides a method for drug screening and disease model construction of liver organoid, relates to the technical field of medical research, and adopts multi-modal data acquisition, fusion and intelligent analysis and quantum computing processing to optimize comprehensive application of data, so that the richness, accuracy and analysis efficiency of the data are remarkably improved, and the risk of drug screening and disease model construction of liver organoid is reduced. Multi-source data of genomics, transcriptomics and the like are collected comprehensively, an accurate research system of immune-hepatic disease interaction based on organoid is constructed, an in-vivo complex immune-hepatic disease microenvironment can be highly simulated, the proportion and activation state of immune cells are accurately regulated and controlled in an in-vitro model, functional and phenotypic changes of the immune cells are monitored in real time, and the immune-hepatic disease interaction accuracy is improved. According to the present invention, the interaction mechanism between the immune cells and the liver organ cells is deeply revealed, such that the accurate information basis is provided for the accurate determination of the drug action target, the development of the innovative drug for the immune check point or tumor microenvironment regulation is easily achieved, and the pertinence and the success rate of the drug research and development are substantially improved.

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

The invention discloses a lung adenocarcinoma prognosis risk prediction model and a construction method and application thereof, and belongs to the technical field of biomedical detection. The lung adenocarcinoma (LUAD) prognosis model is successfully constructed by systematically analyzing the immune infiltration related gene (CAFRG) of tumor-associated fibroblasts (CAF), and the application value of the lung adenocarcinoma (LUAD) prognosis model in prediction of patient prognosis is verified. The CAFRG risk score is negatively related to the immune microenvironment score and is remarkably related to immune checkpoint gene expression, which suggests that a high-risk patient may have the characteristic of immune escape. Furthermore, based on TIDE tool analysis, the patients in the low-risk group have more active T cell immune response. The risk score is also closely related to the sensitivity of antitumor drugs, especially Doramapimod. Therefore, a new theoretical basis is provided for personalized treatment of lung adenocarcinoma, and a new direction is provided for future clinical research.

The invention provides an immunodetection method of a multi-index immune checkpoint detection kit, which belongs to the technical field of immunodetection and comprises three main stages of sample preparation, immune reaction and data analysis. The method comprises the following steps: firstly, carrying out centrifugal separation to obtain a plasma sample, and preparing a fluorescent microsphere coupled capture antibody and biotin labeled detection antibody compound; then carrying out immune reaction, forming a sandwich type immune complex through specific binding, and adding streptavidin marked by phycoerythrin for signal amplification. Detecting a fluorescence signal by adopting a flow cytometer to obtain an original data matrix; a contribution feature vector, a utility feature vector and an expression feature matrix are extracted through a feature decomposition algorithm, and a deep learning model of a total-score-total structure is established for data analysis. Finally, a detection report containing a quantitative result, an importance score and reliability evaluation is generated, and the technical problem that in the prior art, the analysis accuracy of a multi-index immune checkpoint detection result is insufficient is solved.

The invention belongs to the technical field of engineered probiotics, and particularly relates to engineered probiotics for radiosensitization and tumor metabolism regulation as well as a preparation method and application of the engineered probiotics. The engineering probiotics comprise probiotics and core-shell type metal nanoparticles which are loaded on the probiotics and are synthesized through a biological directional mineralization effect; the core of the core-shell type metal nanoparticle is a palladium element, and the outer layer of the core-shell type metal nanoparticle is a palladium element and a gold element. The engineering probiotics provided by the invention have excellent enzyme catalysis performance and can target and retain in tumor sites, and through the synergistic effect of all components in the engineering probiotics, adenosine metabolism is effectively inhibited, secretion of pro-inflammatory cytokines is enhanced, tumor microenvironment is promoted to be converted into an inflammatory state, up-regulation of immune checkpoints is inhibited, and the immune checkpoints are inhibited. And T cells are inhibited from being transformed into depletion phenotype and transformed into effect type from depletion type. After the SBRT and the immune checkpoint inhibitor are combined for use, the growth of tumors can be effectively inhibited, and the effect of enhancing immune radiotherapy is achieved.

A photosensitizer chimera targeting PD-L1 protein, and a preparation method therefor and a use thereof. The photosensitizer chimera is of an X-R-G structure, wherein X is a photosensitizer unit, R is a linker, G is a polypeptide unit targeting PD-L1 protein, the photosensitizer is a porphyrin photosensitizer, and the excitation light wavelength of the photosensitizer is longer than 550 nm; the molar absorption coefficient at the maximum absorption wavelength longer than the wavelength of 550 nm is greater than 1000 M -1cm-1; the quantum yield of a triplet state exceeds 0.01; the linker is selected from the following structural formulas, wherein the amino side of the linker is connected to the photosensitizer unit, the carboxyl side of the linker is connected to the polypeptide unit, and n is an integer of 0-50; the binding constant of the polypeptide and h-PD-L1 is less than 20 µm. Combination therapy of immune checkpoint blockade and cytotoxicity induced by the photosensitive chimera based on photodegradation of PD-L1 protein in PD-1 / PD-L1 can cause stronger immune response than monotherapy, and thus the photosensitive chimera has great potential in enhancing antitumor therapy.

Provided is use of a new immune checkpoint PIEZO1 pathway in tumor T-cell therapy. A PIEZO1 inhibitor can be used for treating cancers, improving the killing ability of T cells, and improving the therapeutic effect of an immune checkpoint inhibitor.

The invention provides application of TRMT61A and its inhibitor tetramethylthiuram disulfide in tumor immunotherapy, and relates to the technical field of biological medicine, clinical research proves that RNA m1A methyltransferase TRMT61A is highly expressed in tumor tissues and is related to poor prognosis of tumor patients, and can be used as one of tumor therapy targets. Meanwhile, high expression of the TRMT61A is related to poor prognosis of a tumor patient receiving anti-PD-1 immunotherapy, and after anti-PD-1 antibody immunotherapy is carried out on the patient with low TRMT61A expression level in the tumor of the patient, pathological complete relief is easier. Tetramethylthiuram disulfide inhibits TRMT61A, inhibits m1A modification regulation of TRMT61A on PD-L1 mRNA, increases PD-L1 protein expression, and is combined with a PD-1 antibody drug to significantly enhance the immunotherapy effect of the anti-PD-1 immune checkpoint drug in treating malignant tumors.

The present invention provides multiplex assays for improved scoring of tumour tissues stained with an immune checkpoint protein such as VISTA. Methods of ranking multiple tumour tissues and of diagnosing cancer patients are also provided. The methods disclosed are also useful for identifying patient responsive to anticancer therapy.

The invention relates to the technical field of biological medicine, and particularly discloses application of spirolactone in preparation of a synergist of an immune checkpoint inhibitor. The application finds that spirolactone can enhance the effect of the immune checkpoint inhibitor on treating liver cancer, has no toxic or side effect on animals, and improves the tumor killing ability of infiltrating NK cells. Animal experiments show that the progress of the liver cancer can be remarkably inhibited by combining the spirolactone with the immune checkpoint inhibitor, and the tumor killing capability of infiltrating NK cells can be improved by combining administration, so that the spirolactone can be used as an auxiliary medicine for clinically improving or enhancing the immune checkpoint to treat the liver cancer (HCC).

The invention provides a nucleic acid aptamer agonist conjugate as well as a preparation method and application thereof. The nucleic acid aptamer agonist conjugate is prepared by coupling a nucleic acid aptamer, a connexon and an STING agonist, the nucleic acid aptamer agonist conjugate can be used as a medicine to recognize a target spot on the surface of a tumor cell in a targeted manner and enter the cell to start a cGAS-STING signal channel so as to realize an anti-tumor effect. The variety of STING agonists and the variety of connexons are also screened, so that the aptamer agonist conjugate not only has the advantages of easiness in transmembrane and cell entry, strong tumor permeability, long half-life period, small toxic and side effects and the like, but also has a strong inhibition effect on triple-negative breast cancer. The aptamer agonist conjugate can also be combined with an immune checkpoint blocking therapy to further realize long-acting and efficient inhibition of tumor growth.

The present disclosure is generally related to methods of reducing the frequency and / or severity of adverse events in subjects undergoing checkpoint inhibitor immunotherapy using natural killer (NK) cells.

To create an antibody that inhibits an immune checkpoint function based on interaction between VSIG4 and Siglec-7 and exhibits antitumor activity, and to provide an anti-tumor immune response activator which includes the antibody as an active ingredient.SOLUTION: The present invention provides an anti-tumor immune response activator including an antibody that inhibits intermolecular interaction between VSIG4 and Siglec-7 or a functional fragment thereof.SELECTED DRAWING: Figure 9

Aspects of the disclosure relate to methods for enhanced combination immune checkpoint inhibition therapy utilizing RNAi, including by intratumoral administration of chemically-modified double stranded nucleic acid molecules directed against genes encoding PD-1, BRD4, CTLA-4, TIGIT, and / or CBL-B.

Disclosed are compositions, kits, and methods for identifying genes that are involved in T-cell trafficking. In particular, the compositions, kits, and methods may be used to identify genes involved in T-cell trafficking and / or infiltration into tumors such as genes that encode immune checkpoint regulators and / or stimulatory agents. The disclosed compositions, kits, and methods utilize the Sleeping Beauty® transposon system in a mouse tumor model to identify genes that are involved in T-cell trafficking and infiltration into tumors. The genes identified in the disclosed methods may provide immunotherapy targets in the tumor microenvironment. The identified genes may be utilized in order to develop therapies that enhance T-cell trafficking and infiltration into tumors and / or T-cell killing of tumors such as in chimeric antigen receptor (CAR) T cell therapies.

Provided are an immune checkpoint inhibitor containing as an active ingredient a substance that inhibits the interaction of integrin and immunosuppressive receptor (referred to hereinafter as LILR) B3 and a therapeutic agent for immune checkpoint-related disease containing as an active ingredient a substance that inhibits the interaction of integrin and LILRB3.

The invention relates to a preparation method and application of a targeted pancreatic cancer immune checkpoint diagnosis and treatment integrated nanoprobe, which can realize integration of sonodynamic therapy and MRI imaging of pancreatic cancer cells with high expression of VISTA, realize targeted SDT therapy of pancreatic cancer and visual evaluation of the therapeutic effect, have good biological safety, and can be applied to diagnosis and treatment of pancreatic cancer cells with high expression of VISTA. SDT visual treatment of targeted pancreatic cancer is realized at a cellular level, and SDT combined immunotherapy of pancreatic cancer is realized at an animal level. The method comprises the following steps: (1) preparing Fe3O4 nanoparticles by using a solvothermal method; (2) preparing Fe3O4 (at) SiO2 nano particles; (3) preparing Fe3O4 (at) SiO2 (at) TiO2 nano particles; (4) preparing Fe3O4 (at) TiO2 by adopting an alkaline hydrothermal corrosion auxiliary crystallization method; and (5) modifying the nanoprobe with a VISTA antibody through an electrostatic adsorption method, and finally successfully constructing the garland-shaped nanoprobe.

Embodiments of the present disclosure relate to a composition that comprises a recombinant plasmid (RP) with a sequence of nucleic acids. The sequence comprise a start region, an end region and an insert positioned between the start region and the end region. The insert encodes for a sequence of micro interfering ribonucleic acid (miRNA) that may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is an immune checkpoint protein.

Described herein are fusion proteins comprising an extracellular domain of an immune checkpoint receptor and a cytoplasmic domain of an activating receptor. Also described herein are fusion proteins comprising a cytoplasmic domain of an immune checkpoint receptor and an extracellular domain of an activating receptor. The present disclosure further provides methods of use of such fusion proteins.

The present invention provides a system for drug delivery that utilizes a hydrogel to deliver a bioactive agent to stimulate three-level lymphatic structure formation within a mature tumor and enhance immune checkpoint blocking. Provided herein is an injectable hydrogel that can stimulate the formation of immune structures within a tumor, improve cancer prognosis and therapeutic response. The invention provides application of the system to treatment of cancer. Methods of making the drug delivery system are also provided.

The invention relates to the technical field of antibodies, in particular to a complex of an antibody and IL-2 and application of the complex. The present invention provides a complex of an antibody and IL-2, comprising: an immune checkpoint antibody and an IL15R [alpha] receptor domain covalently linked, and an IL-2 / 15 chimera (S-unit molecule) or a variant thereof non-covalently complexed with the IL15R [alpha] receptor domain. By means of the creative design, IL-2 molecules are gradually dissociated from the complex to achieve a short half-life period, and an immune checkpoint antibody achieves a long half-life period due to the fact that an Fc structural domain is combined with FcRn circulation. As a result, the half-lives and administration dosages of the two molecules can be matched to each other.

The invention discloses a PD1 gene engineering exosome preparation for cancer immunotherapy and a preparation method of the PD1 gene engineering exosome preparation. The invention provides a method for preparing an exosome for expressing PD1, and further provides any one of the following applications of the exosome as a drug carrier, delivery of drugs, preparation of tumor treatment products, preparation of postoperative tumor recurrence resistant products, preparation of postoperative tumor metastasis resistant products and the like. Genetically recombinantly engineered exosomes can be used to enhance the response of cancer immune checkpoint blocking therapies. The research also provides a new strategy with a prospect, and is used for enhancing the PD1 / PDL1 treatment effect, and postoperative tumor recurrence or metastasis is resisted by reconstructing the immunity of a patient, so that the overall prognosis is consolidated.

The invention discloses application of a TEAD1 palmitoylation inhibitor VT103 in preparation of a PD-1 immune checkpoint antibody sensitization drug, and belongs to the technical field of tumor immunotherapy. It is confirmed for the first time that TEAD palmitoylation inhibition can overcome immunotherapy drug resistance of MSS tumors by regulating and controlling the state of the microsatellite, a brand new action target is provided for clinical development of immune checkpoint inhibitor sensitizing drugs, microsatellite instability is induced firstly, then immunotherapy is carried out in a combined mode, and therefore the treatment effect is improved.

To provide means of suppressing immune checkpoints based on signaling pathways independent of the PD1 pathway, and to provide methods for in silico search for genes belonging to signaling pathways independent of the PD1 pathway.SOLUTION: Provided are an immune checkpoint inhibitor and anticancer drug resistance suppressant, including a kynureninase inhibitor. Also provided are a method for predicting the prognosis of a cancer patient or the sensitivity of a cancer patient to an anticancer drug based on kynureninase activity, and a method for screening genes related to immune checkpoints based on mutual information.SELECTED DRAWING: None

The invention belongs to the technical field of pharmaceutical preparations, and relates to a bionic nano-drug delivery system for targeted regulation of microglial cell immune function, in particular to a bionic nano-drug delivery system for targeted regulation of microglial cell immune function and having the effect of an immune checkpoint inhibitor and application of the bionic nano-drug delivery system in brain glioma immunotherapy. The drug delivery system is a bionic nano drug delivery system prepared from an oleanolic acid nanocrystal core (OA-core), an M0 or M2 type macrophage membrane and an acid-sensitive lipid material connected with immune checkpoint antagonistic polypeptide. The bionic nano-drug delivery system constructed by the invention can realize co-loading of small molecule drugs and polypeptide drugs and precise delivery and graded release of focus parts, regulates and controls the brain glioma immune process in a multi-target manner, synergistically enhances the anti-glioma immune effect, and has a wide application prospect.

The present disclosure provides prophylactic methods for using an immune checkpoint inhibitor to prevent neoplasia in a Lynch Syndrome subject that lacks detectable tumors and has not received a prior anti-cancer therapy such as immunotherapy. In some embodiments, the Lynch Syndrome subject does not harbor germline mutations in POLE or POLDI and / or comprises a hereditary mismatch repair deficient (dMMR) germline mutation.

Provided are cytokine fusion proteins comprising a first cytokine fused to a second cytokine, for example, interleukin-2 (IL-2) or interferon-β (IFN-β) fused to the N-terminus of tumor necrosis factor-α (TNF-α), and related compositions and methods of use thereof for treating cancers, either as standalone agents or in combination with autologous tumor vaccines and / or immune checkpoint modulatory agents.

Provided herein are method for identifying a subject as having or at risk of having myocarditis and / or myositis based on the detection of the level of cytotoxic CD8+ T-cells and / or inflammatory myeloid cells, and / or on the detection of the level of expression of a TNF signaling via NFκB, an interferon-α signaling, an interferon-γ signaling, an IL2 / STAT5 signaling, a hypoxia signaling and / or a complement signaling in CD45+ immune cells. The identification of such patients is used in methods of treating a subject having or at risk of having myocarditis and / or myositis, methods of treating cancer, and methods of treating immune checkpoint therapy (ICT)-related myocarditis and / or ICT-related myositis. The methods of treatment include the administration of a therapeutic compound to inhibit IL-1β and TNF.

The invention discloses a method for enhancing mechanical force of CAR-T cells on target cells to overcome mechanical immune checkpoints of SFs and application, and relates to the technical field of crossing of immunotherapy and biomechanics, in particular to CAR-T cells targeting fibroblast activated protein. The invention discloses a CAR-T (chimeric antigen receptor T-T) cell and SFs (small-form-factor s) DNA (deoxyribonucleic acid) nano connector for connecting the CAR-T cell with the SFs, the formation of a CAR cluster and mechanical force transmission are promoted by shortening the membrane spacing of an immune synaptic interface to 16-28nm, the DNA nano connector is formed by self-assembling complementary tetrahedral DNA structures, and the TDS comprises a single-stranded DNA vertex S4 with the length of 24-58 nucleotides. According to the method for enhancing the mechanical force of the CAR-T cells on the target cells to overcome the mechanical immune checkpoints of the SFs and the application, the escape and killing problems of the soft target cells are solved, the soft target cells are efficiently removed, and the killing rate of the CAR-T cells treated by DNJ-17 on the SFs is remarkably increased.

The invention relates to the technical field of biological medicine, in particular to application of cordyceps sinensis polysaccharide in preparation of a medicine for enhancing the treatment effect of a PD-1 antibody on tumors. According to the invention, the cordyceps sinensis polysaccharide and the PD-1 antibody are combined for use, so that the treatment effect on colorectal cancer is remarkably improved. The combined application of the cordyceps sinensis polysaccharide and the PD-1 antibody not only utilizes the immunoregulation effect of the cordyceps sinensis polysaccharide and the immune checkpoint blocking effect of the PD-1 antibody to improve the tumor inhibition rate, but also discloses the ability of the cordyceps sinensis polysaccharide to regulate the composition and function of intestinal flora, which is a key mechanism for enhancing the curative effect of the PD-1 antibody. According to the invention, a synergistic effect mechanism during combined application is defined for the first time, and a new theoretical basis is laid for future research and drug development.