101 results about "Cell response" patented technology

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 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.

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 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.

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 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).

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.

A method of preparing cells for therapeutic use is provided in which a population of progenitor cells is cultured under cell culture conditions that promote progenitor cell differentiation, the cell culture conditions comprising the presence of G-CSF, GM-CSF, IL-3, and TNF; to produce a population of granulocytic cells. The produced granulocytic cells are useful in methods of treatment, including the treatment of cancer and infections, and the modulation of inflammatory cell responses.

Systems and methods for identifying cellular responses to candidate drugs, including treatment cycling, are described. These systems and methods utilize rapid response readout in combination with gentle removal and / or exchange of the analyte fluid. The systems and methods can be used, for example, in T-cell epitope mapping, T-cell diagnostics, and other cell-based high-throughput screening methods.

A method for preparing cells for therapeutic use is provided, comprising culturing a population of progenitor cells under cell culture conditions that promote progenitor cell differentiation, including the presence of G-CSF, GM-CSF, IL-3, and TNF, to generate a population of granulocyte-producing cells. The generated granulocyte-producing cells may be useful in therapeutic methods, including the treatment of cancer and infections, and may also be useful in modulating inflammatory cell responses.

The present disclosure provides compositions and methods useful for inducing a Th1 cell response in a subject suffering from Hepatitis B. As described herein, the compositions of the disclosure comprise HBsAg having S, Pre-S1 and Pre-S2 proteins and an aluminum phosphate adjuvant. In a preferred embodiment, the immunogenic composition comprises at least 20 μg / ml of HBsAg antigen and the amount of non-adsorbed antigen is at least 30%.

The present disclosure provides tumor neoantigenic peptide sequences and nucleotide sequences encoding such peptide sequences; a vaccine or immunogenic composition capable of raising a specific T-cell response comprising one or more of the neoantigenic peptides, or comprising nucleic acid encoding one or more of the neoantigenic peptides; an antibody, or an antigen-binding fragment thereof, a T cell receptor (TCR), or a chimeric antigen receptor (CAR) that specifically binds such neoantigenic peptides; methods of producing such antibodies, TCRs or CARs; polynucleotides encoding such neoantigenic peptides, antibodies, CARs or TCRs, optionally linked to a heterologous regulatory control sequence; immune cells that specifically bind to such neoantigenic peptides; and dendritic cells or antigen presenting cells that have been pulsed with one or more of the neoantigenic peptides; and methods of using such products in particular therapeutic uses of these products.

The invention relates to a cell culture reactor in a full temperature control mode, and relates to the technical field of cell culture reaction equipment. The cell culture reactor in the full temperature control mode comprises a shell, a heating cavity is formed in the shell, a bottom plate and a bottom heater are arranged in the heating cavity, the bottom plate is used for placing a cell reaction bag, the bottom heater is used for heating the bottom plate, a cavity heating mechanism is further arranged in the shell, and the cavity heating mechanism is used for heating the cell reaction bag. And the cavity heating mechanism comprises a heating fan, and the heating fan is used for heating gas in the heating cavity. The device has the effect of ensuring the heating uniformity of the cell reaction bag.

The present disclosure provides tumor neoantigenic peptide sequences and nucleotide sequences encoding such peptide sequences; a vaccine or immunogenic composition capable of raising a specific T-cell response comprising one or more of the neoantigenic peptides, or comprising nucleic acid encoding one or more of the neoantigenic peptides; an antibody, or an antigen-binding fragment thereof, a T cell receptor (TCR), or a chimeric antigen receptor (CAR) that specifically binds such neoantigenic peptides; methods of producing such antibodies, TCRs or CARs; polynucleotides encoding such neoantigenic peptides, antibodies, CARs or TCRs, optionally linked to a heterologous regulatory control sequence; immune cells that specifically bind to such neoantigenic peptides; and dendritic cells or antigen presenting cells that have been pulsed with one or more of the neoantigenic peptides; and methods of using such products in particular therapeutic uses of these products.

To provide vaccines and methods.SOLUTION: Described herein are methods for identifying optimized antigenic pathogen polypeptides capable of inducing a broadly neutralizing immune response and associated T-cell responses to a pathogen, and nucleic acid sequences encoding such polypeptides. Also described are methods for determining whether a broadly neutralizing immune response is induced in a subject following immunization with an optimized antigenic pathogen polypeptide or a nucleic acid encoding the optimized pathogen polypeptide. Further described are nucleic acid molecules, polypeptides, vectors, cells, fusion proteins, pharmaceutical compositions, and their use as vaccines against pathogens, especially against emerging or re-emerging pathogens (particularly RNA viruses).SELECTED DRAWING: None

The invention is directed to methods for determining antigen-specific T cells. In some embodiments, methods of the inven-tion may be implemented by the steps of reacting under interaction conditions one or more antigens with T cells in a plurality of subsets of a tissue sample, such as peripheral blood; sorting antigen-interacting T cells from other T cells; separately sequencing for each subset recombined nucleic acid encoding a segment of a TCR chain from a sample of T cells prior to exposure to antigen and from a sample off cells isolated based on their interaction with antigen, thereby form-ing a clonotype profile for the former sample and the latter sample for each subset; and identifying as antigen-specific T cells those T cells associated with a clonotype whose fre-quency increases in the latter sample relative to its frequency in the former sample.

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.

A mesoscopic unit cell analysis method for bending mechanical behaviors of a three-dimensional braided composite material relates to the field of mechanical property analysis, and comprises the following steps: obtaining mesoscopic characteristics and geometric parameters of a material, and establishing a mesoscopic unit cell finite element model with in-plane periodicity and thickness consistent with that of a sample; the method comprises the following steps: enabling a four-point bending sample to be equivalent to an in-plane periodically distributed thin plate structure, establishing association between macroscopic thin plate deformation and mesoscopic unit cell deformation based on a homogenization method, and deducing periodic boundary conditions; applying a boundary condition on the mesoscopic unit cell finite element model to simulate a mesoscopic mechanical response under a four-point bending load; and macroscopic bending performance parameters are obtained through microcosmic stress field homogenization treatment. According to the method, the in-plane periodic mesoscopic unit cell finite element model with the thickness consistent with that of the sample is established, the periodic boundary condition and the homogenization method are combined, macroscopic thin plate deformation and unit cell mesoscopic response are associated, and the applicability problem caused by non-periodicity of a traditional unit cell model in the thickness direction under the bending load is solved.