45 results about "Granzyme" patented technology

The invention discloses a preparation method and application of a granzyme B response near-infrared two-region ratiometric fluorescent probe (DCGA). The DCGA combines the NIR-II dual-emission fluorescence characteristic of rare earth ions with a ratio-type signal response mode, the sensitivity and signal stability of in-vivo fluorescence imaging are greatly improved, ultralow or enhanced F1060nm fluorescence signals are respectively shown before and after interaction with granzyme B (GzmB), F1525nm fluorescence signals are almost kept unchanged, and the DCGA can be used for detecting the in-vivo fluorescence imaging of the granzyme B (GzmB). Therefore, the self-calibration ratio fluorescence imaging GzmB activity change is realized. The DCGA is applied to tumor treatment of immunotherapy drugs, and responders and non-responders of immunotherapy can be distinguished in a non-invasive early stage through ratio fluorescence signals of the DCGA. Therefore, the fluorescent probe can be used as an effective GzmB active NIR-II ratio fluorescence imaging tool, and is expected to provide powerful support for immunotherapy research, precision medicine and personalized diagnosis and treatment.

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

The invention relates to a three-dimensional cellular microcompartment or an assembly of three-dimensional cellular microcompartments of ovoid, cylindrical, spheroidal or spherical shape or substantially ovoid, cylindrical, spheroidal or spherical shape, the smallest dimension of which is between 200 and 400 μm, comprising an external hydrogel layer defining an internal part, said internal part having a granzyme B content of less than 1 μg / ml of medium and comprising between 500 and 5000 lymphocytes forming a three-dimensionally grouped culture. The invention also relates to a method for producing such a microcompartment or microcompartment assembly.

To provide a composition for forming enzyme-containing particles which enables simple and inexpensive formation of enzyme-containing particles, enzyme-containing particles having excellent hydrolyzability in the presence of water, a molded body which can achieve both excellent durability of a resin and excellent biodegradability, and an enzymatic decomposable resin composition which enables simple and inexpensive formation of the molded body.SOLUTION: A composition for forming enzyme-containing particles contains a modified polymer which enables formation of a polymer that has a polymerizable group and is hydrolyzable, an enzyme which does not decompose a polymer that is obtained by polymerization of the modified polymer and is hydrolyzable, and a polymerization initiator for polymerizing the modified polymer, where the modified polymer contains modified polycaprolactone having a polymerizable group.SELECTED DRAWING: Figure 3

The purpose of the present invention is to provide: an antibody that binds to CD25 and has internalizing activity; an antibody-drug conjugate that contains the antibody and has antineoplastic activity; a pharmaceutical product that uses the antibody-drug conjugate and has a therapeutic effect on tumors; and a pharmaceutical product that uses the antibody-drug conjugate and has a therapeutic effect on tumors. A method for treating a tumor using an antibody-drug conjugate or a pharmaceutical product; and the like. The present invention provides a CD25 antibody or an antigen-binding fragment of the antibody, which is characterized by (1) having no IL-2 blocking ability and (2) having an activity of internalizing into a CD25-expressing cell by binding to CD25. The antibody or the antigen-binding fragment of the antibody and a cytotoxic active compound are made into a conjugate, thereby exhibiting the ability to remove regulatory T cells and / or the ability to promote the proliferation of granzyme-positive CD8-positive cells.

An object of the present invention is to prepare a novel food-derived exosome composition and to provide a cancer inhibitor or an agent for preventing decrease in tissue elasticity or an agent for improving elasticity containing a novel active ingredient. As a result of intensive studies on the purification process, the inventors have found that an exosome can be extracted from yeast mash and moromi by a unique production method. The inventors have found that the exosome recovered from the yeast mash and the moromi has a cancer cell proliferation inhibition ability, an ability to promote increase in the amount of granzyme, and an ability to promote expression of collagen and elastin. Accordingly, the inventors provide a composition for treating or preventing cancer and an agent for preventing decrease in tissue elasticity or an agent for improving elasticity, containing exosomes derived from yeast mash and moromi of sake.

The invention relates to the technical field of biomedical materials, and discloses a preparation method of an injectable composite support material for denasal endoscopic skull base reconstruction, and the method comprises the following steps: preparing a component A aqueous solution and a component B non-aqueous phase paste; the component A comprises a hyaluronic acid derivative grafted with dopamine and alginate. The component B is paste in which calcium salt solid-phase particles, enzyme, polymer microspheres and nanoscale fumed silica are dispersed in a non-aqueous phase dispersion medium, and the nanoscale fumed silica is used for inhibiting solid-phase particle sedimentation. According to the method, the prepared component A and the prepared component B are respectively packaged in a double-component application device. According to the invention, active components are isolated in a non-aqueous phase, and controllable operation time, firm adhesion to tissues and mechanical support provided by polymer microspheres are realized through a staged curing mechanism of ionic crosslinking and enzymatic crosslinking during use; the problem that an existing material is difficult to consider storage stability, operation convenience and composite functionality at the same time is solved.

The invention belongs to the field of immunology, and relates to an immune cell-derived extracellular vesicle and application thereof, the targeted extracellular vesicle is generated by immune cells, and the membrane of the targeted extracellular vesicle comprises at least one protein with a membrane fusion function and at least one targeting part. A nucleic acid sequence containing a targeting antibody and a protein with a membrane fusion function is used as an exogenous gene, immune cells are used as production cells to prepare the EV, and the EV which expresses the targeting antibody on the membrane surface and is high in membrane fusion efficiency is prepared. The EV internally contains granzyme and other toxic molecules, the targeting molecules are combined with tumor cell surface antigens, membrane fusion protein promotes the membrane fusion rate, the EV can directly deliver the granzyme and other toxic molecules to tumor cell cytoplasm, and the toxic molecules play an excellent tumor killing effect. The result shows that the apoptosis rate of the immune EV in the experimental group for remarkably inducing the apoptosis of the SK-BK-3 cells in vitro can reach 85-95%.

Cyclic peptides that bind to granzyme B and are useful for imaging granzyme B, salts thereof, pharmaceutical compositions comprising the same, diagnostic and therapeutic uses, and methods of making such compounds are disclosed. Compounds useful as radiotracers for positron emission tomography (PET) and / or single photon emission tomography (SPECT) imaging are also provided. Further disclosed is the use of the compounds as imaging agents for granzyme B.

The invention relates to: a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising an IL-2 protein and a CD80 protein; and a method for preparing natural killer cells by using same. Particularly, a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising IL-2 or a variant thereof and CD80 or a fragment thereof, of the present invention; promotes the proliferation of natural killer cells, induces the expression of CD16 and NKp46, and increases the expression and secretion of granzyme B and perforin, thereby being effectively usable in the preparation of natural killer cells having an excellent anticancer immune function.

The application belongs to the technical field of biological medical materials, and particularly relates to a granzyme B specific response nano probe and a preparation method and application thereof. The granzyme B specific response nano probe comprises a near-infrared down-conversion nano probe, and a pentapeptide IEFDK-fluorescence quenching modification group is modified on the surface of the near-infrared down-conversion nano probe; the pentapeptide IEFDK-fluorescence quenching modification group is derived from a pentapeptide IEFDK-fluorescence quencher with a structure shown in formula (1). The granzyme B specific response nano probe provided by the application can specifically respond to granzyme B, realize immune effect monitoring of a tumor site, and thus realize detection of tumor immune responses after different radiotherapy schemes are processed. Formula (1).

An object of the present invention is to prepare a novel food-derived exosome composition and to provide a cancer inhibitor or an agent for preventing decrease in tissue elasticity or an agent for improving elasticity containing a novel active ingredient. As a result of intensive studies on the purification process, the inventors have found that an exosome can be extracted from yeast mash and moromi by a unique production method. The inventors have found that the exosome recovered from the yeast mash and the moromi has a cancer cell proliferation inhibition ability, an ability to promote increase in the amount of granzyme, and an ability to promote expression of collagen and elastin. Accordingly, the inventors provide a composition for treating or preventing cancer and an agent for preventing decrease in tissue elasticity or an agent for improving elasticity, containing exosomes derived from yeast mash and moromi of sake.

The invention belongs to the technical field of pharmaceutical compositions for removing senescent cells, and discloses a pharmaceutical composition for removing senescent cells and a preparation method and application thereof, and the pharmaceutical composition for removing senescent cells contains NK cells and fisetin. According to the pharmaceutical composition for removing senescent cells, the fisetin and the NK cells are combined for use, on one hand, the fisetin can enable the NK cells to easily recognize senescent cells; on the other hand, fisetin can relieve inhibition of SASP factors on NK cell activity, enough amount of cytotoxic particles such as perforin and granzyme are synthesized and released in NK cells, the killing efficiency on senescent cells is high, fisetin can directly trigger an apoptosis pathway of the senescent cells, and the effect of killing the senescent cells is achieved. The NK cells release cytotoxic particles to further accelerate death of the senescent cells, and fisetin and the NK cells have a synergistic effect, so that the senescent cell clearing efficiency is high.

The invention provides a porcine circovirus type 5 Cap protein, a virus-like particle, an elisa plate, an ELISA kit and application thereof, and belongs to the technical field of animal viruses. The invention provides a porcine circovirus type 5 Cap protein with an amino acid sequence as shown in SEQ ID NO. 1. The porcine circovirus type 5 Cap protein provided by the invention has the advantages of stable structure and good antigenicity, can be specifically combined with a circovirus type 5 antibody in a serum sample, and can be self-assembled into 60 virus-like particles. The ELISA plate and the ELISA kit for detecting the porcine circovirus type 5, provided by the invention, have the advantages of strong specificity and high sensitivity, and can accurately detect whether a blood sample contains the porcine circovirus type 5 or not. The porcine circovirus type 5 virus-like particle provided by the invention has the advantages of high yield, good uniformity and strong stability, and can be subsequently prepared into a porcine circovirus type 5 subunit vaccine.

Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and / or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin / granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and / or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.

Compounds of Formula (I) and Formula (II), which are capable of binding to granzyme B. Also provided herein are pharmaceutical compositions comprising such for use in, for example, imaging Granzyme B and / or treating immunoregulatory abnormalities.

The invention is directed to compounds of Formula (I) and their pharmaceutically acceptable salts, which may be suitable for imaging Granzyme B activity and hence are useful in binding and imaging Granzyme B in patients with cancer or inflammatory diseases.

Compositions and methods are provided for the cell-mediated targeted killing of diseased cells based on the presence of an intracellular antigen, rather than a surface-bound marker. The targeting cells are modified to express a cytotoxic protein that is delivered into a targeted cell, and after delivery is selectively activated by the presence of a cytoplasmic protein of interest. In one embodiment of the invention, the cytotoxic molecule is a Granzyme B (GrB) polypeptide. In the compositions of the invention, GrB is modified to render its cytotoxic enzymatic functions inactive, until the presence of an intracellular antigen unlocks the GrB molecule to enable enzymatic activities.

Novel cyclic peptides that bind to granzyme B and may be suitable for imaging granzyme B, their salts, pharmaceutical compositions containing them, diagnostic and therapeutic uses, and methods for producing such compounds are disclosed. Additionally, compounds useful as radiotracers for positron emission tomography (PET) and / or single photon emission computed tomography (SPECT) imaging are provided. The use of the compounds as imaging agents for granzyme B is further disclosed.

This invention relates to a granzyme B-targeting complex, a radiopharmaceutical, and their imaging applications in tumor immunotherapy, belonging to the field of nuclear medicine diagnostics. The complex is covalently modified, triggering a covalent group proximity effect by recognizing the binding of a peptide to granzyme B, achieving irreversible covalent linkage between the probe and the target protein. This significantly enhances the probe's selective retention at the target site and extends the imaging time window. After radionuclide labeling, the complex can be prepared into a radiopharmaceutical for nuclear medicine imaging; the labeling process is simple and exhibits good stability. This radiopharmaceutical allows for non-invasive, specific, and quantitative monitoring of granzyme B expression levels via PET or SPECT, reflecting the activity status of immune cells in vivo. This invention has significant clinical application value and promising prospects for the early and accurate prediction and dynamic monitoring of tumor immunotherapy efficacy.

The invention discloses application of ganoderenic acid A in enhancing the killing function of T lymphocytes. The ganoderenic acid A is lanolin alkyne alkyl type triterpenoid, and it is proved that the ganoderenic acid A can promote T lymphocytes to release granzyme, perforin and interferon within the concentration range of 5-10 [mu] M, and then the killing function of the T lymphocytes is promoted. The early foundation is laid for the ganoderenic acid A to become an immunoregulation small molecule medicine in the future, and it is indicated that the ganoderenic acid A is expected to become a recognized XinJin immune activator.

The invention provides application of B cell granzyme B as a target spot in preparation of a product for treating myocardial infarction or heart failure, and belongs to the technical field of biomedicine. The invention provides the effect of inhibiting the expression of B cell granzyme B and treating myocardial infarction or heart failure for the first time. Animal experiments show that by inhibiting the expression of B cell granzyme B, the cardiac function after myocardial infarction can be improved, the expression of heart failure indexes after myocardial infarction can be reduced, the expression of inflammatory factors in the heart after myocardial infarction can be inhibited, and cardiac fibrosis caused by myocardial infarction can be improved. The application has the advantages that the myocardial infarction or the heart failure can be improved by inhibiting the B cell-derived granzyme B for the first time, a new prevention and treatment drug research and development approach and a drug action target are provided for the treatment of the myocardial infarction and / or the heart failure, and the application value is very important.

The invention relates to the technical field of tumor immunotherapy, in particular to application of an AKR1B1 inhibitor and an immune checkpoint inhibitor in preparation of antitumor drugs and a pharmaceutical composition containing the AKR1B1 inhibitor and ICIs. After the AKR1B1 inhibitor is combined with the immune checkpoint inhibitor, the following technical effects are achieved: 1, the tumor growth is obviously inhibited: in a mouse breast cancer model and a lung cancer model, the tumor growth inhibition rate of the epalrestat single drug is about 30%; the inhibition rate of a PD-1 single drug is about 30%-40%; the inhibition rate of combined treatment is remarkably improved to 65%, and an obvious synergistic anti-tumor effect is shown. 2, the anti-tumor immune response is enhanced, and the activity of CD8 positive T cells can be remarkably improved by the epalrestat single drug; the combined treatment can improve the proportion of cytokines (such as granzyme B and interferon g) secreted by CD8 positive T cells in tumors. 3, the safety is high: under the administration dosage, no obvious drug toxicity is observed in the heart, liver, spleen, kidney and lung of the mouse;

Compounds of Formula (I) and Formula (II) that are capable of binding to granzyme B. Also provided herein are pharmaceutical compositions comprising the compounds, for example, for imaging and / or treating immunomodulatory abnormalities of granzyme B.

This invention discloses a method and application for single-cell nucleus dissociation suitable for tissue sections. The method includes: S1, obtaining tissue sections to be processed, attaching them to a carrier surface, and then adding an incubation buffer for incubation; wherein the incubation buffer contains Tris-HCl, NaCl, MgCl2, micro / nano particles, RNase inhibitors, bovine serum albumin, and a nonionic surfactant; S2, transferring the incubated product to a centrifuge tube, gently mixing by pipetting to obtain a nucleus dissociation buffer; S3, filtering and centrifuging the nucleus dissociation buffer, collecting the precipitate, and resuspending it to obtain a nucleus suspension. This single-cell nucleus dissociation method is mild and efficient. The nucleus suspension obtained using this method has high purity of single nuclei and low cytoplasmic debris, and can be directly used for downstream omics analyses such as high-throughput single-cell nuclear sequencing, spatial transcriptomics, and ATAC-seq, demonstrating high application value.

The disclosure describes immune cells that express granzyme protease(s), methods of producing and methods of using the immune cells for the treatment of cancer.

The application discloses a fluorescence hybridization chain reaction biosensor based on the existence of granzyme B and application thereof, and realizes real-time detection of T cell effector molecules by establishing a fluorescence hybridization chain reaction biosensor based on the existence of active granzyme B, and has the characteristics of short amplification time, simple operation, high amplification efficiency, simple reaction system and high economic benefit. By introducing peptide nucleic acid into the hybridization chain reaction system, the cutting of the substrate by granzyme B is successfully used as the starting recognition event of the hybridization chain reaction, and after the cutting of the peptide substrate in the peptide nucleic acid by granzyme B, the foothold is exposed, the strand displacement reaction is mediated, the fluorescence signal is restored after amplification, and a new strategy of using the hybridization chain reaction for detecting active cytokines is provided. The strategy makes the hybridization chain reaction using fluorescence as a signal output mode applicable to active protein detection, and has the advantages of a simple reaction system, few operation steps and low detection cost.

The invention relates to a method for activating NK (Natural Killer) cells and application thereof, in particular to application of an LINC02577 inhibitor in preparation of an NK cell activating medicine. Experiments show that the expression quantity of the LINC02577 is reduced in the NK cell activation process, so that the LINC02577 can be used for preparing a kit for detecting NK cell activation; meanwhile, the knock-down LINC02577 is found to be capable of effectively promoting expression of NK cells CD107a and granzyme B, promoting secretion of IFN-gamma and TNF-alpha and promoting the killing activity of the NK cells on leukemia cells, so that the knock-down LINC02577 can be used for preparing the medicine for promoting activation of the NK cells, and the NK cells with the knock-down LINC02577 can be used for preparing the medicine for treating leukemia.

The invention belongs to the technical field of medicines, and particularly relates to application of indole-3-carbinol in preparation of thyroid cancer immunotherapy drugs. Through cell and animal experiments, the indole-3-methanol can be used for remarkably enhancing the curative effects of thyroid cancer immunotherapy and targeted therapy by inhibiting the activity of WWP1 ubiquitin ligase, stabilizing STAT6 protein expression, inhibiting TDO2-mediated tryptophan metabolism and remodeling an immune microenvironment. Indole-3-A is clear in action mechanism and high in safety, and has important clinical application value. In a mouse model, single use of indole-3-carbinol can significantly inhibit thyroid cancer growth and enhance CD8 + T cell infiltration and granzyme B activity, and the effect of indole-3-carbinol is equivalent to that of a PD-1 monoclonal antibody; the combination of indole-3-methanol and PD-1mAb can synergistically enhance the anti-tumor immune response and significantly inhibit tumor growth. The pharmaceutical composition is especially suitable for immunotherapy of drug-resistant or advanced refractory cases, and shows a remarkable synergistic effect compared with the existing therapy.