140 results about "Cell response" patented technology

The invention belongs to the field of biological medicine, and particularly relates to a mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition and application of the mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition in tumor treatment, and amino acid sequences of the neoantigen polypeptide are shown as SEQ ID No.2, 13, 16 and 17. Four tumor neoantigen polypeptides really having immunogenicity are obtained through screening, the obtained tumor neoantigens are compatible with PolyI: C to prepare the vaccine preparation, and after mice are treated by the MC38 tumor vaccine preparation, the growth of tumors can be effectively inhibited; and the survival time of the mouse is prolonged, and the new antigen vaccine preparation generates very effective T cell reaction in the tumor-bearing mouse body.

Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.

The invention discloses a culture medium optimization method and system based on metabolic stimulation. The method comprises the following steps: (1) constructing a relation model of component concentration difference and cell response amount at each culture moment relative to an initial culture moment; (2) taking a preset cell response amount or a weighted value of a plurality of preset cell response amounts as an optimization target, and searching an optimal component concentration difference by adopting a global optimization algorithm; and (3) determining a control quantity according to a preset culture scheme by taking the optimal component concentration difference as a control target, obtaining a culture solution component addition concentration of the culture medium or the culture medium series under the culture scheme by adopting an optimal control algorithm, and developing a culture medium formula of the preset culture scheme. According to the method, synergistic adjustment among components of the culture medium at different culture moments is considered; modeling analysis is carried out on data by adopting machine learning, so that the research and development period of culture medium optimization can be shortened, and repeated tests are reduced. Meanwhile, nonlinear correlation among different components in the culture medium can be considered.

In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.

The invention discloses an alpha nuclide drug in-vitro cellular response prediction method and system based on multi-module mathematical modeling and a medium, and the method comprises the steps: constructing a basic parameter input module, a pharmacokinetic prediction module, a cell absorbed dose calculation module and a biological effect prediction module which are connected in sequence; a three-compartment dynamical model and a micro-dose learning point kernel convolution and DNA damage repair dynamical model are integrated, and full-chain and quantitative simulation from drug distribution, microscopic energy deposition to cell survival is achieved. The method overcomes the defects that an existing empirical model cannot accurately reflect the high LET characteristic of alpha particles, neglects the bystander effect and repair dynamics and the like, and the prediction precision is remarkably improved. According to the method, the curative effects of different drugs, cell lines and dosage schemes can be quickly simulated on a computer, the research and development cost and period are greatly reduced, and an efficient theoretical tool is provided for new drug screening and dosage optimization.

To identify lipid metabolites that control Th17 cell differentiation and lipid biosynthetic enzymes involved therein, and based on that, to provide a screening method for a therapeutic agent for diseases caused by excessive Th17 cell responses.SOLUTION: Provided is 1-oleoyl-lysophosphatidylethanolamine (LPE(1-18:1)) as a lipid metabolic product that controls Th17 cell differentiation. Since LPE(1-18:1) binds to RORγt with high specificity and promotes differentiation into Th17 cells, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained by selecting a compound that inhibits the binding of LPE(1-18:1) to RORγt. Also provided are five lipid metabolic enzymes (Gpam, Gpat3, Lplat1, Pla2g12a, and Scd2) that are responsible for the biosynthesis of LPE(1-18:1) and control Th17 cell differentiation. By selecting a compound that inhibits the activity or expression of these lipid metabolic enzymes, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained.SELECTED DRAWING: None

In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.

The present disclosure relates to compositions and methods of altering an immune cell response in a subject in need thereof, said method comprising administering an inhibitory agent that inhibits VPS72 activity and / or expression in an immune cell of the subject.

In various embodiments immunogenic nanoparticles are provided that are capable of raising an immune response directed against SARS-CoV-2. In certain embodiments the immunogenic nanoparticles comprise mRNA multi-epitope vaccines that can be used in combination with or independent of other covid-19 vaccines (e.g., the spike protein mRNA vaccine(s)) to invoke a strong CD8+ or CD4+ T-cell as well as neutralizing antibody producing B-cell responses. In certain embodiments this vaccine is based on the rational combination of well-conserved T- and B-cell epitopes identified COVID-19 and viral variants.

Systems, compositions, and methods are described that utilize three dimensional tumor models incorporating tissue barrier (such as a stromal barrier) around tumor cells in culture, which permit replication in vivo immune cell response to tumor cells. Such tumor models are used to accurately assess appropriate therapeutic modes and protocols that are likely to be effective against the individual's tumor. Such tumor models can be used to selectively expand immune cells that are responsive to tumor cells utilized in the model. Such an expanded population of immune cells can subsequently be utilized therapeutically.

T cell responses are exquisitely antigen-specific and directed against peptide epitopes displayed by human leukocyte antigen (HLA) on the surface of presenting cells. In particular, class II HLA (HLA-II) is remarkably polymorphic, which allows for presentation of diverse peptide antigens to T cells, but also forms the basis for genetic associations with diverse immunopathologies across the spectrum of infectious disease and autoimmunity. Here, Applicants employ monoallelic immunopeptidomics to retrieve over 200,000 unique peptides presented by 41 HLA-II heterodimers covering major alleles across diverse ancestries. Applicants leveraged this expansive dataset to develop computational models that predict peptide antigens based on HLA-II binding properties and infer informative features of the protein antigens from which these peptides derive. Combining both peptide and (contextual) protein features, Applicants develop Context Aware Predictor of T cell Antigens (CAPTAn) to discover novel T cell epitopes from prokaryotes in the human microbiome and the viral pandemic pathogen SARS-COV-2.

A system and method for analyzing mechanical properties of biological tissues combines light-sheet fluorescence microscopy with mechanical perturbation capabilities. The system integrates a MEMS-based compression device, high-speed light-sheet scanner, and digital image correlation analysis to characterize viscoelastic properties of three-dimensional cellular structures. The system enables quantification of spatially-resolved mechanical characteristics and cellular responses through volumetric strain analysis, correlating mechanical properties with fluorescence-based cellular markers. Implementation with maternal-fetal interface models demonstrates capabilities in analyzing tissue mechanics during cellular invasion processes. The system provides applications in studying mechanical interactions in biological processes including embryonic development, cancer metastasis, and wound healing. The disclosed methodology enables unprecedented analysis of mechanical property dynamics at cellular interfaces in three-dimensional tissue environments.

The present invention relates to the treatment of Tauopathies. In this study, the inventors worked on an optimized treatment of Tauopathies, including AD and primary Tauopathies. Previously, the inventors evidenced that Tau pathology is associated with deleterious T-cell-mediated processes that contribute to promote Tau-related detrimental neuroinflammation and cognitive deficits. Considering the unique capacity of immunosuppressive Tregs to inhibit both CD4+ and CD8+ T cell responses, the inventors raise the hypothesis that amplifying Tregs may allow controlling Tau-driven T-cell-mediated detrimental processes in the course of AD and other Tauopathies. They thus evaluated preclinically the impact on disease progression of an optimized IL-2-based Treg-targeting immunomodulatory treatment in the THY-Tau22 mouse model of Tauopathy. They chronically treated THY-Tau22 mice with an optimized IL-2-based treatment, i.e. complexes of IL-2 and anti-IL-2 antibodies (termed herein IL-2C) in order to modulate Tau-associated detrimental T cell responses. Their data supports that this treatment amplifies Tregs more efficiently and selectively than "regular" low dose IL-2 treatment. Furthermore, they hereby showed that IL-2C has a beneficial effect on cognitive deficits since treated THY-Tau22 mice tend to acquire and retain spatial information more potently than untreated littermates. Thus, the invention relates to an IL-2 / anti-IL-2 complex (IL-2C) for use in the treatment of Tauopathies.

A chimpanzee adenovirus vector from newly discovered and isolated chimpanzee adenovirus with unique HVR sequences and a method of its construction and application thereof, with higher viral titer, and provides a method for determining its viral titer. The chimpanzee adenovirus circular vector is constructed through a shuttle plasmid, and knocks out E1 and E3 to construct a replication-defective chimpanzee adenovirus vector. The chimpanzee adenovirus vector described in this article has no preexisting antibody in the population, and the knockout of E1 and E3 is safe. At the same time, it is significantly different from human adenovirus type 5 E1 in 293 cells, which can greatly avoid recovery mutation (RCA) and make it safer. The novel coronavirus vaccine has strong stability and does not cause mutations after multiple passages, and it can induce strong humoral immunity and cellular response in mouse models.

The invention provides a Chinese herbal medicine composition blood vessel protection effect prediction method and system based on deep learning. The method comprises the following steps: firstly, acquiring spectral data of Chinese herbal medicines, and separating characteristic signals of active components through an optical filtering unit; a principal component dimension reduction module and a molecular polarity sensing layer of a deep neural network are utilized to analyze phase offsets of different polarity components, feature weights are dynamically adjusted, a correlation model of spectrum parameters and active component concentrations is established, and a component characteristic spectrum is generated. And then, dynamically distributing the wave band weight of the characteristic spectrum through a multi-channel attention module, comparing the wave band weight with a target activity threshold interval in a vascular cell response database, and optimizing the characteristic spectrum. And finally, inputting the optimized characteristic spectrum into a neural network model, and outputting a quantized value of the blood vessel protection effect after matching characteristic dimensions. The spectral characteristics of the Chinese herbal medicines are dynamically analyzed through deep learning, and the blood vessel protection effect is accurately quantified.

Methods are provided for the step-wise generation of endothelial cells. Also provided are methods for generating pure populations of such cell types and derivatives thereof. The instant disclosure also provides methods of screening for cellular responses of the generated cell types and derivatives thereof. Treatment methods making use of the generated cell types and derivatives thereof are also provided. The instant disclosure also provides systems, compositions, and kits for practicing the methods of the disclosure.

The present disclosure relates to a method for designing a personalized cancer vaccine, using a B cell-reactive neoantigen, the method comprising the steps of: receiving a peptide sequence extracted from cancer tissue and allelic sequence data of B cell receptors; calculating the preferential binding strength between amino acids in the peptide sequence and allelic sequences of B cell receptors; and calculating B cell epitope prediction scores by inputting the preferential binding strength between amino acids to a trained neural network model.

A polymeric nanoparticle is disclosed which comprises:(i) at least one disease-associated antigen which is capable of producing a T-cell response, wherein the disease-associated antigen is encapsulated in the nanoparticle;(ii) at least one adjuvant; and(iii) a dendritic cell targeting moiety which is attached to the outer surface of the nanoparticle.Use of the nanoparticle for treating diseases associated with abnormal cell growth or an infection is also disclosed.

In order to provide a new agent for hair pigmentation treatment in subjects, the present invention suggests an active agent for use in the treatment of hair pigmentation, wherein the active agent activates, enhances, inactivates, blocks or dampens the cellular response of the taste receptor TAS2R50 or interferes with the expression of said receptor. Furthermore, the present invention is directed to the use of said active agent as a medicament, a cosmetic or a food supplement in therapeutical or non-therapeutical treatment of hair pigmentation. In addition, the invention is directed to a corresponding cosmetic or medical hair pigmentation regulating or modulating composition or food supplement.

The invention provides a cell reaction bag with a double-gas-path ventilation device, the cell reaction bag comprises a reaction bag body, a ventilation device and a stirring device, the ventilation device comprises a ventilation disc, the ventilation disc is provided with a first hole group and a second hole group, and the ventilation disc is internally provided with a first channel and a second channel which are respectively communicated with the first hole group and the second hole group; the bottom of the ventilation disc is provided with a first air inlet and a second air inlet which are communicated with the first channel and the second channel respectively. According to the ventilation device disclosed by the invention, two groups of holes with different sizes and corresponding channels are arranged, so that double-gas-path ventilation is formed, different gases can be respectively introduced, large bubbles are generated on the outer side of the ventilation disc, and micro bubbles are generated on the inner side of the ventilation disc; the gas dissolving efficiency is improved, uniform gas distribution is ensured, and uniform growth of cells is facilitated; different requirements on gases such as oxygen and carbon dioxide in the cell culture process can be accurately controlled, and a more suitable gas environment is provided for cell growth.

The present application relates to an imaging quality test method, device and equipment for an X-ray linear array detection device, wherein the method includes: determining the direction of motion of an X-ray linear array detection object and the detection line position of the X-ray linear array detection device; performing clarity detection of the optical path imaging of the X-ray linear array detection device based on the direction of motion and the detection line position; performing signal-to-noise ratio, noise signal mutual interference and pixel response consistency detection of the optical path imaging of the X-ray linear array detection device respectively; and collecting the results of the signal-to-noise ratio detection, clarity detection, noise signal mutual interference detection and pixel response consistency detection to obtain the imaging quality test result of the X-ray linear array detection device. During the whole process, the imaging quality of the X-ray linear array detection device is respectively tested for clarity, signal-to-noise ratio, noise signal mutual interference and pixel response consistency, and the imaging quality test of the X-ray linear array detection device is performed from four dimensions.

The present invention discloses a method for amplifying or detecting full-length transcriptome cDNA containing full-length poly(A). The method includes: (1) single-cell reaction preparation; (2) terminal extension: using 10×barcoded gel beads with Poly(dT) as a template to extend the ends of transcripts with poly(A) to obtain single-stranded product 1; (3) template replacement: performing reverse transcription on the product 1, adding 3 bases C to the 3' end after the reverse transcription product; and adding a TSO primer for reaction to obtain product 2; (4) PCR amplification: performing PCR amplification on the product 2. The present invention improves the library construction throughput of single-cell full-length transcriptomes and fills the technical gap that current single-cell transcriptome detection cannot detect full-length poly(A).

To provide peptide-based vaccines for inducing immune response and production methods and uses thereof.SOLUTION: The present disclosure relates to novel peptide-based vaccines, methods of manufacturing the novel peptide-based vaccines and uses thereof for delivering peptide antigens to induce an immune response, and in particular a T cell response to a subject. The present inventors have developed novel compositions and methods of manufacturing peptide-based vaccines that overcome at least one of the limitations of current peptide-based vaccine approaches. The novel peptide-based vaccine compositions and methods of manufacturing disclosed herein account for the variability in the physical and chemical properties of peptide antigens and are therefore generalizable for any peptide antigen.SELECTED DRAWING: None

Disclosed herein are branched chain amino acid transaminase 1 (BCAT1) inhibitors and uses thereof. More specifically, disclosed are BCAT1 inhibitors that limit amino acid metabolism essential for CD4+ T-cell responses and their use in preventing, improving, or treating inflammatory disease or autoimmune disease. By identifying that BCAT1 acts as a major regulator in the inflammatory response of CD4+ T-cells, it is possible to regulate the inflammatory response by CD4+ T cells secreting interleukin-17 (IL-17), which is a major immune cell of autoimmune diseases, by utilizing a BCAT1 inhibitor.

The invention provides a novel vaccine adjuvant and application of the novel vaccine adjuvant in preparation of the vaccine adjuvant. The BCG-PSN and vaccine induced RBD specific IgG antibody and neutralizing antibody level are equivalent to those of an aluminum adjuvant, the BCG-PSN and vaccine induce Th1 biased T cell reaction, the induced T cell response level is obviously higher than that of the aluminum adjuvant, and K18-hACE2 mice are protected from being affected by Delta variant induced lung lesions. As a vaccine adjuvant, BCG-PSN has wide compatibility and safety, and has no toxic or side effect.

Provided are a broad-spectrum anti-COVID-19 vaccine immunogen composition, and the preparation and a use thereof. Specifically, provided is an immunogen composition, comprising an RBD recombinant chimeric antigen, wherein the chimeric antigen comprises S protein RBD domains from two or more COVID-19 subtypes, or functional fragments thereof. The immunogen composition can further comprise a multimerization domain and a T-cell immunogen domain. Further provided are a use of the immunogen composition, a corresponding encoding molecule therefor, a vector, and / or a host cell in preparing an anti-COVID-19 vaccine. The vaccine can induce a broad-spectrum protective effect against a prototype strain and various currently prevalent variants, and can also elicit a potent cross-protective T-cell response, thereby achieving effective and broad-spectrum prevention against COVID-19 and achieving a protective effect against other coronaviruses.

The invention relates to the technical field of active ingredient extraction, and particularly provides an extraction method for classifying and screening active ingredients, raw materials are subjected to low-temperature freeze-drying pretreatment by adopting supercritical CO2, and treatment is performed for 4-6 hours under the conditions of minus 40-minus 20 DEG C and 8-12 MPa, so that the active ingredients are reserved to the greatest extent; through gradient ultrasonic-assisted extraction of ultrapure water, a 50% ethanol solution and a 95% ethanol solution, step-by-step separation of water-soluble, alcohol-soluble and fat-soluble components is realized; carrying out multi-dimensional purification by using a composite chromatographic column containing a 0.2 mu m ceramic membrane layer, a macroporous adsorption resin layer and a sephadex layer; a two-channel biosensor array is adopted to synchronously detect a cell response signal and a molecule binding signal, and components with the activity intensity reaching 80% or above are screened; and finally, carrying out vacuum rotary evaporation concentration and spray drying to obtain a finished product, and completing system purity verification through a high performance liquid chromatography-mass spectrometry technology to form a complete quality control system.

The invention discloses a laminar flow micro-fluidic chip and method for detecting spatial heterogeneous drug distribution influence, the chip comprises a fluid layer and a control layer, the fluid layer comprises a first main inlet and a second main inlet, the fluid layer further comprises a plurality of independent cell culture chambers of an array, the control layer comprises a control valve inlet and a pneumatic valve array, and the control valve inlet is communicated with the pneumatic valve array. The independent cell culture chamber is composed of a concave cavity, the independent cell culture chamber is provided with two semicircular enclosures, a first channel inlet and a second channel inlet are formed in the independent cell culture chamber, and peristaltic pump subunits are arranged on the first channel inlet and the second channel inlet. Laminar flow control is achieved by integrating the pneumatic valve and the peristaltic pump, and chemical gradient generation and cell response monitoring of micron-sized spatial resolution are achieved through automatic control.

A method for measuring kinetics of Ca2+ flux in differentially responding T cells that form monolayer on the glass surface in response to antigenic peptides or live target cells comprising: immobilizing T cells labeled with Ca2+ sensitive fluorophore on the glass bottom of a well, covered with capturing antibody or a capturing protein that bind to non-stimulatory T-cell surface receptor; adding to the well a single or multiple peptide epitopes that binds to the cell surface MHC molecules to be presented for recognition by cognate T cells; the stimulatory signal could also be delivered by live target cells that display peptide epitope(s); wherein the recognition of stimulatory of pMHC by the peptide specific T cells leads to increase of intracellular Ca2+ level and fluorescence intensity in the responding T cells, which is then identified after the subtracting fluorescence intensity for every T cell before and after the addition of the peptide antigens; scoring each responding T cell into a category according to three categories including: a rapid and sustained T-cell response, an oscillatory response, or a delayed and oscillatory response; and measuring changes in number of an individual T cells with increased intracellular fluorescence as function of time provides the kinetic curve of the TCR-mediated Ca2+ signaling.

In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.