72 results about "Intravenous IG" patented technology

The invention provides a multifunctional self-bionic nano vaccine for treating breast cancer. The multifunctional self-bionic nano vaccine comprises MnOx nano particles serving as inner cores and fusion cell membranes wrapping the surfaces of the inner cores of the MnOx nano particles, the fused cell membrane is obtained by fusing a remodeled 4T1 cell membrane and a remodeled DC cell membrane. According to the invention, the nano vaccine can play an immunotherapy role in treating breast cancer under the condition of subcutaneous injection. After subcutaneous peritumoral injection, the multifunctional autologous bionic nano vaccine can target tumor tissues to play an in-situ chemical power treatment role, chemotactic to drainage lymph nodes to realize efficient T cell immune response to play an immunotherapy role, and main organs of the whole body are less gathered, so that the vaccine is safe and reliable; the SPNE prepared in the prior art can cause a certain liver aggregation effect after intravenous injection, and great toxic and side effects are generated.

Described herein are methods for treating antibody mediated rejection of transplanted organs using inhibitors of IL-6. In one embodiment, the IL-6 inhibitor is Tocilizumab and is administered simultaneously or sequentially with intravenous immunoglobulin (IVIG).

Disclosed in the present invention are a targeted immunotolerance vaccine, a preparation method therefor, and use thereof. The present invention separately modifies a rheumatoid arthritis-related autoantigen peptide and CTLA4 Ig with DSPE-PEG (DP) to prepare a targeted formulation DP-antigen peptide and a targeted formulation DP-CTLA4, which are then mixed to obtain the vaccine. The vaccine described in the present invention, after intravenous injection, binds to albumin in vivo by means of DSPE, "hitchhiking" on albumin to target and enrich in inflammatory lesions, the spleen, the liver, and other tolerance-inducing sites, inhibiting T cell activation, and inducing anergy and apoptosis of rheumatoid arthritis autoantigen-specific T cells, thereby achieving immunotolerance treatment and prevention of rheumatoid arthritis.

The invention discloses a brain glioma animal model construction method based on an AAV mediated immune microenvironment. The method comprises the following steps: selecting an immunodeficient mouse at the right age; human CD34 + hematopoietic stem cells are injected for immune system reconstruction; human CD45 + immune cells in the peripheral blood PBMC are detected; the method comprises the following steps: selecting tumor tissues with high-expression brain glioma marker genes, carrying out rapid qPCR (quantitative polymerase chain reaction) or targeted RNA-seq immunohistochemical multiple verification, and screening consistent tumor tissues; the method comprises the following steps: physically dicing tumor tissues, treating the tumor tissues with pretreatment liquid, digesting the tumor tissues into single-cell suspension, and inoculating the single-cell suspension into a mouse cranium; an AAV vector carrying a specific immune regulation gene is injected into the tail vein of the mouse, and the brain glioma immune microenvironment is regulated; when it is observed that the tumor tissue grows stably and has immune cell infiltration characteristics, construction of the brain glioma animal model is completed. Compared with an existing model, the brain glioma model which is more stable, more scientific and closer to the human immune background is provided, and the brain glioma model is suitable for related immunotherapy drug screening and mechanism research.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

Provided herein are gene editing systems and compositions directed to effectuate in vivo edits in the LPA gene. Treatment or prevention of cardiovascular disease through disruption of the production of apo(a) through genetic editing and the reduction of the blood lipoprotein(a) [Lp(a)] concentration is disclosed herein. Disclosed are nickase-based gene editing systems designed to effectuate the installation of insertions and / or deletions (indel variants) and / or non-synonymous variants in the coding sequence of LPA. The nickase-based gene editing systems generally comprise one or more mRNAs that encode one or more nickases and a plurality of guide oligonucleotides (e.g., gRNAs) and may be delivered in vivo to a mammalian subject in need thereof via a suitable delivery system, such as lipid nanoparticles (LNPs) (with or without GalNAc targeting moieties) intravenously, or otherwise, administered to a patient as potentially a once-and-done therapeutic. The manufacturing, use, and formulation of the gene editing systems and compositions are also disclosed.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APCs.

The invention relates to a cell membrane bionic drug-loaded carbon dot nano-material as well as a preparation method and application thereof. The nano-composite is prepared by the following steps: preparing carbon dots, cross-linking to form a reduction responsive carbon dot nano-cluster, sequentially loading chemotherapeutic drugs and coating a cancer cell membrane to form a nano-vaccine. After the nano vaccine is injected into the body of a mouse through caudal vein, the enrichment of the nano vaccine in a tumor part can be enhanced by utilizing the active tumor targeting characteristic of a cancer cell membrane, and tumor cells can be induced to generate immunogenic death through carried chemotherapy drugs and photothermal therapy, so that chemotherapy / photothermal / immune combined therapy on tumors is realized; the obvious anti-tumor effect is realized. In addition, as a nano vaccine, after subcutaneous injection, the nano vaccine can also utilize the tumor antigen carried by a cancer cell membrane and the adjuvant characteristics of the carbon dots to activate the anti-tumor immunity of an organism so as to prevent tumors, and has potential clinical application value.

To provide a pharmaceutical formulation comprising trehalose for use in treating myopathies, neurodegenerative diseases, or tauopathies associated with abnormal protein aggregation.SOLUTION: A pharmaceutical formulation comprising a therapeutically effective amount of trehalose is provided, wherein the pharmaceutical formulation is for use in a method for treating a disease associated with abnormal protein aggregation and / or inclusion bodies formation in myocytes, neurons, or extracellular compartments, or for alleviating at least one symptom associated therewith in a human subject in need thereof, the method comprising intravenously administering to the subject a pharmaceutical formulation comprising 0.1% (w / v) to 50% (w / v) of trehalose. An injectable aqueous pharmaceutical formulation comprising a therapeutically effective amount of trehalose is also provided.SELECTED DRAWING: None

The invention discloses a preparation method and application of tumor exosome loaded gamma delta T cells. The tumor exosome-loaded gamma delta T cells are researched to be used for treating lung cancer, after the gamma delta T cells and the tumor cell exosome-loaded gamma delta T cells are co-cultured with lung cancer tumor cells respectively, a large number of tumor cell exosome-loaded gamma delta T cells surround the tumor cells, the tumor cells are attacked, and the tumor cell exosome-loaded gamma delta T cells are used for treating lung cancer. And the gamma delta T cells do not attack surrounding tumor cells. The tumor cell exosome loaded gamma delta T cells are intravenously injected into multiple lung cancer patients, compared with the prior art, the proportion of CD3 + and CD4 + positive cells is remarkably increased after 4 cycles and 6 months after treatment, the proportion of CD8 + positive cells is remarkably reduced, the ratio of CD4 + / CD8 + is remarkably increased after 6 months, and the number of NK cells is remarkably increased after 4 cycles after treatment, so that the tumor cell exosome loaded gamma delta T cells can be used for treating the lung cancer patients. The tumor exosome loaded gamma delta T cell has a good anti-tumor effect.

This invention discloses a method for preparing NK cells, the NK cells obtained thereby, and their applications. The method includes: sorting NK cells from peripheral blood of an allogeneic donor; culturing them in a serum-free medium containing CD3 monoclonal antibody, CD16 antibody, and IL-2, without the need for a feeder layer; preferably, IL-21 is added for amplification on days 3-5 of culture, and the cells are cultured for 20-40 days. This method yields non-genetically modified NK cells, among which CD56... bright The NK cells comprise >90% of the cell line and highly express a variety of activating and functional molecules. These NK cells effectively clear Aβ oligomers and senescent cells, and alleviate neuroinflammation. In treatment, intracranial injection achieves equivalent or better efficacy with only about 1 / 10th the dose administered intravenously, significantly clearing Aβ deposits in the brains of AD model mice and improving pathology.

A stable pharmaceutical formulation according to the present invention comprises: (A) Ixekizumab; and (B) a histidine buffer. A stable pharmaceutical formulation according to the present invention comprises an antibody, has excellent long-term storage stability on the basis of having excellent stability especially under accelerated conditions and severe conditions, and can be administered intravenously or subcutaneously.

Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response during intravenous PEGylated uricase therapy in gout patients is provided. Routine SUA monitoring can be used to identify patients receiving PEGylated uricase who may no longer benefit from treatment and who are at greater risk for infusion reactions.

The present invention provides a preparation process of a human immunoglobulin preparation for intravenous injection, which belongs to the field of protein production technology. The preparation process provided by the present invention comprises: dissolving the component II+III precipitate with a precipitation dissolving solution containing 0.8%-1.2% sodium dihydrogen phosphate and 0.66%-1.0% sodium citrate, adding low-temperature ethanol, adding a filter-aid mixed powder for filter pressing, wherein the weight ratio of diatomaceous earth, cellulose and silicon dioxide in the filter-aid mixed powder is 4-5:2-3:1-1.5. The human immunoglobulin preparation for intravenous injection prepared by the present invention has an anti-complement activity of only 5%-7%, has good thermal stability, and a purity of up to 99.3%-100%.

The present invention provides intravenous pharmaceutical compositions comprising engineered plant virus-based nanoparticles for the treatment or prevention of autoimmune conditions. The nanoparticles display immunodominant peptides that induce immune tolerance in a subject when administered intravenously. The invention further provides methods of manufacturing virus-based nanoparticles, including production in plant expression systems and optional viral inactivation, to render them suitable for therapeutic use in mammals. Also provided are methods of intravenous administration of the pharmaceutical compositions to a subject in need thereof for treating or preventing autoimmune conditions.

The invention relates to the technical field of tumor cell killing, in particular to a method for in-vivo detection of the tumor cell killing effect of NK cells, and the method comprises the following steps: S1, taking killing of male C57BL / 6 mouse NK cells on Hela cells and other types of human-derived tumor cells under in-vivo conditions as a model, and taking the Hela cells as a contrast; s2, grouping the selected mice, and correspondingly performing intraperitoneal injection of isotype IgG, an anti-NK1.1 antibody and an anti-mouse NKG2D monoclonal antibody; s3, preparing a cell mixed solution of to-be-detected tumor cells and Hela cells; s4, injecting the cell mixed liquid into the body of the mouse in a caudal vein injection manner; s5, killing each group of mice, and taking lungs to prepare a single-cell suspension; s6, detecting the number of CFSE positive cells and the number of PKH26 positive cells in the mouse lung single-cell suspension by adopting a flow cytometer; and S7, calculating the survival rate of the tumor cells to be detected. The method well solves the problem that the killing effect of the NK cells on the human tumor cells is difficult to accurately and truly evaluate in the prior art.

The invention belongs to the field of nucleic acid editing, and particularly relates to the technical field of regularly clustered interval short palindromic repeat (CRISPR). Specifically, Cas9 or smaller Cas-SF01 (a Cas12i3 variant) is utilized to reasonably design and construct a compact mRNA-delivered epigenetic suppressor in an engineering manner, and an optimized mRNA structure, lipid nanoparticle (LNP) delivery, OFF-E-V2 mRNA optimized by single intravenous injection and selected guide RNA (gRNA) targeting mouse PCSK9 are combined, so that circulating PCSK9 protein is reduced by about 90%, corresponding LDL-C level is reduced by about 55%, and the PCSK9 protein is reduced by about 90%. The effect lasts for at least 180 days. Compared with a corresponding object based on Cas9, an editor based on Cas-SF01 shows higher specificity, and off-target methylation events are fewer. The optimized LNP formulations also exhibit good safety. These findings establish a powerful and versatile platform for promoting a transient delivery-based engineered mRNA editor to achieve precise and lasting epigenetic silencing in vivo therapy.

The present invention relates to the treatment of diseases associated with inflammation including solid cancers. More particularly, certain methods relate to the administration (e.g., intravenously) of polyhedrin protein (PODS) crystals for the delivery of one or more therapeutic proteins. This enables targeted release of low doses of the therapeutic protein at sites of the disease.

IT-139, sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)], is an intravenously administered small molecule compound. In preclinical anti-tumor and mechanism of action studies, IT-139 showed activity against a broad range of tumor types, including those which are resistant to standard anti-cancer agents (e.g., platinums, vinca alkaloids, taxanes, anthracyclines). This activity is believed to arise from IT-139's novel mechanism of action that targets the GRP78 pathway. It was found that up-regulation of GRP78 is a key cancer cell survival pathway. Downregulation of GRP78 using IT-139 removes this resistance pathway allowing for chemotherapy and immuno-oncology agents to be more effective in treating cancer.

The present application provides compositions and methods for increasing safety, selectivity, and efficacy of transduction of human cells, including human long-term repopulating and hematopoietic stem cells (LT-HSC) and human cancer cells, by adenovirus vectors through multiplexed targeting of virus attachment and internalization receptors. Multiplexing targeting Ad vector receptor specificities through the combination of i) restricting fiber-specific attachment receptors, ii) deleting the RGD amino acid motif from the penton base protein, and iii) inserting into Ad penton base protein of peptides that lack the RGD amino acid motif and enable vector interaction with integrin classes expressed on target cells, allows for the improvement of safety, selectivity, and efficacy of vector-mediated transduction of human cells in vitro and after intravenous vector administration in vivo.

This invention discloses a method for improving a mouse model of ANCA-associated vasculitis induced by anti-GBM antibodies, relating to the field of animal model construction. The method involves subcutaneously injecting mice with 20 μg rMPO on Day 0; administering 10 μg rMPO on Day 7; subcutaneously injecting 250 μg / kg GCSF daily from Day 11 to 15; and injecting 100 μl of goat anti-GBM serum via the tail vein on Day 16 to obtain the improved mouse model. This method improves the existing anti-GBM antibody-induced ANCA-associated vasculitis mouse model by injecting GCSF. This model enhances the disease severity in ANCA-associated vasculitis mice, specifically reflecting the disease in renal pathology and proteinuria, making the differences more obvious and effectively improving the success rate of model establishment.

Provided are methods for clinical treatment of complement-associated conditions comprising administering to the patient an anti-C5 antibody, or antigen binding fragment thereof, wherein the anti-C5 antibody, or antigen binding fragment thereof, is administered (or is for administration) subcutaneously according to a particular clinical dosage regimen (i.e., at a particular dose amount and according to a specific dosing schedule). In one embodiment, the patient has previously been treated with eculizumab (SOLIRIS®) or ravulizumab (ULTOMIRIS®); particularly intravenously administered SOLIRIS® or ULTOMIRIS®.

The present invention discloses a method for constructing an animal model of glioma based on AAV-mediated immune microenvironment, comprising: selecting immunodeficient mice of appropriate age; injecting human CD34+ hematopoietic stem cells for immune system reconstruction; detecting human CD45+ immune cells in peripheral blood PBMC; selecting tumor tissues that highly express glioma marker genes, performing rapid qPCR or targeted RNA-seq immunohistochemistry multiple verification, and screening tumor tissues that meet the requirements; physically cutting the tumor tissue and treating it with a pretreatment solution, digesting it into a single cell suspension, and inoculating it into the mouse's skull; injecting an AAV vector carrying a specific immune regulatory gene into the mouse's tail vein to regulate the glioma immune microenvironment; when the tumor tissue is observed to grow stably and have immune cell infiltration characteristics, the construction of the glioma animal model is completed. Compared with existing models, the present invention provides a more stable, more scientific, and more human immune background glioma model, which is suitable for related immunotherapy drug screening and mechanism research.

The present disclosure provides agents and methods for preventing or treating tuberculosis using RNA. The RNA encoding variants of antigens of Mycobacterium tuberculosis ox of fragments thereof is formulated and administered in a way that the variants are produced by cells of a subject, in particular after intramuscular or intravenous administration of the RNA.

The present invention provides a method for treating an adenovirus infection or a disease associated with an adenovirus infection.　The present invention provides a pharmaceutical composition for the treatment of an adenovirus infection or a disease associated with an adenovirus infection, said pharmaceutical composition comprising a brincidofovir, a pharmaceutically acceptable salt thereof, or a solvate thereof. The treatment comprises: (i) intravenously administering 0.38-0.42 mg / kg of brincidofovir, a pharmaceutically acceptable salt thereof, or a solvate thereof to a human subject twice per week; or (ii) intravenously administering 18-22 mg / administration of brincidofovir, a pharmaceutically acceptable salt thereof, or a solvate thereof to a human subject twice per week.

The invention relates to the use of empty liposomes of defined lipid composition or mixtures of empty liposomes of defined lipid composition and to the use of other lipid bilayers or monolayers of defined lipid composition for the treatment and prevention of bacterial infections. It has been found that such liposomes, in particular a two- and a four-component mixture of liposomes comprising cholesterol and sphingomyelin, liposomes consisting of sphingomyelin, liposomes comprising sphingomyelin and phosphatidylcholine, and liposomes comprising cholesterol and phosphatidylcholine efficiently sequestrate a variety of toxins secreted by bacteria, thus preventing binding of bacterial toxins to target cells and toxin-induced lysis of the target cells. Injected intravenously, liposome mixtures prevented death of laboratory mice infected with lethal doses of Staphylococcus aureus or Streptococcus pneumoniae.

Beta-hydroxybutyrate (BHB) mineral salts and / or beta-hydroxybutyrate (βHB) free acid in combination with 1,3-butanediol (1,3-BD) were used to induce ketosis, achieving blood ketone levels of (2-7 mmol / L), with or without dietary restriction. A combination of the ketogenic compounds, βHB acid and / or βHB salt in together with 1,3BD was more than additive. What has been unknown until now, and what was unexpected is that the specific combination of the partially buffered βHB free acid, (created as a mixture of βHB free acid and βHB salt), together with 1,3-BD in a particular combination is far more than additive. When used together this mixture raises serum levels far higher, up to 70% higher, than would be expected by using 1,3BD together with βHB salt and / or BHB acid. The synergistic combination is 5 times more powerful at raising serum βHB than the enantiomerically pure acid or salt alone and 1.23 times more powerful than the corresponding enantiomerically pure ester compounded from βHB and 1,3-BD. Given the far higher potency, it is now possible to deliver a suitably buffered formulation orally or intravenously in order to achieve a variety of therapeutic benefits without exceeding unsafe salt loads which have in the past, prevented the widespread use of ketone salt and acid. The concurrent co-administration of these compounds is useful to improve metabolic health, cognitive performance, physical performance, enhance disease prevention, mitigate the damage of Ischemia Reperfusion Injury and provide a fuel substrate that is not affected by glucose impairment associated with neurodegenerative diseases. Elevated serum ketones have demonstrated to improve the cognitive function in persons suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's Diseases by providing fuel starved neurons a direct source of fuel, that unlike glucose, is not effected by the glucose and pyruvate dehydrogenase impairments described extensively in the brains of patients suffering from neurodegenerative diseases. This invention results in rapid keto adaptation, which is useful for the avoidance of glucose withdrawal symptoms or “keto flu” commonly experienced by individuals initiating a ketogenic diet. It also minimizes the loss of lean body mass during dietary restriction and does not adversely impact lipid profiles.

The application discloses application of recombinant human USP13 protein in preparation of a drug for treating diabetic cardiomyopathy, and belongs to the technical field of biological medicines.The application first proves that the expression of USP13 in myocardial tissue and serum is significantly reduced under the condition of diabetic cardiomyopathy (DCM); the recombinant human USP13 protein can obviously reduce the level of myocardial cell active oxygen, reduce the expression of NLRP3 inflammasome and active Caspase3 protein in a DCM in-vitro model induced by high sugar / palmitic acid; in a DCM mouse model injected with the recombinant human USP13 protein through a tail vein, myocardial cell apoptosis is inhibited, and the expression of NLRP3 inflammasome and the synthesis of TNF-alpha in the heart of the animal are reduced.USP13 is a human protein, has no obvious toxic side effects, is high in safety, is small in immunological rejection in theory, provides a new effective drug for the clinical treatment of DCM, and has important clinical application value and industrialization prospect.

The application provides a serum proteomics and machine learning-based Kawasaki disease intravenous immunoglobulin (IVIG) resistance biomarker combination and screening method, and belongs to the technical field of medicines. The method comprises the following steps: (1) on the basis of establishing strict inclusion criteria and typing criteria, collecting whole blood samples of IVIG reaction type and non-reaction type Kawasaki disease children before treatment; (2) using DIA proteomics technology for systematic screening and differential protein identification; (3) weighted co-expression network analysis, screening of protein modules significantly related to IVIG non-reaction phenotype; (4) combined with LASSO-Logistic regression and SVM-RFE for multi-step feature screening, identifying five biological markers significantly related to IVIG resistance: PLA2G4A, SNX17, PURB, CERS3 and CASP1 (5) based on the marker expression level, using the pROC package for ROC analysis and calculating AUC; (6) analyzing the correlation between the marker and the clinical index related to Kawasaki disease; (7) after limma processing in the independent transcriptome set GSE18606, using glm to construct a multivariate binary logistic regression prediction model and perform ROC analysis. Through independent transcriptome dataset verification, the biomarker combination screened by the application can realize effective prediction of Kawasaki disease IVIG resistance, and shows good prediction performance and clinical application value.

The application discloses a myocardial ischemic injury marker CAPG and application thereof. The application finds that down-regulation of CAPG expression can improve myocardial cell apoptosis and heart function after myocardial infarction by injecting AAV9-shCAPG virus into the tail vein of a mouse model of myocardial infarction. The application first discloses a new use of macrophage capping protein (CAPG) as a therapeutic target and a diagnostic target of myocardial ischemic injury, provides a new drug action target for diagnosis and treatment of myocardial ischemic injury, and has very important clinical transformation value. As a diagnostic marker of myocardial ischemic injury, CAPG can be conveniently detected by using an existing enzyme-linked immunosorbent assay kit, has the advantage of rapid detection, and can be conveniently detected by only extracting a small amount of peripheral venous blood of a patient.