20 results about "Antigenic stimulation" patented technology

This invention provides a chimeric antigen receptor comprising an NFIX-encoding gene, a self-cleaving peptide sequence F2A, and a CAR-encoding sequence. The NFIX-encoding gene is located upstream and is linked to the CAR-encoding sequence via the self-cleaving peptide sequence F2A. The sequence of the NFIX-encoding gene is shown in SEQ ID NO. 01, and the sequence of the self-cleaving peptide sequence F2A is shown in SEQ ID NO. 03. This invention also provides a chimeric antigen receptor T cell expressing the aforementioned chimeric antigen receptor. This invention further provides the application of the aforementioned chimeric antigen receptor or the aforementioned chimeric antigen receptor T cell in the preparation of drugs for treating cancer. This invention improves the antitumor therapeutic effect of CAR-T cells by introducing the NFIX expression element into engineered T cells, thereby enhancing their functional stability, proliferative capacity, and cytotoxic activity under continuous antigen stimulation.

The invention relates to a method for predicting the evolution of an immune response in a subject towards an effector or suppressor response, based on cellular plasticity determined by the cytokine milieu generated after antigenic stimulation. The invention also allows for evaluating the generation of antigen-specific memory regulatory T cells in the evolution of the immune response. The invention also relates to a kit for carrying out the method according to the invention.

A synthetic cytokine signaling system includes an engineered cytokine receptor chain and optionally an engineered cytokine ligand chain. The engineered cytokine receptor chain encodes a membrane-bound chimeric cytokine receptor comprising an intracellular domain of IL9R and an extracellular domain of a cytokine receptor such as IL2Rβ, IL4R, IL7R, IL9R, IL21R, etc. The engineered cytokine ligand chain encodes a corresponding cytokine ligand that can be membrane bound or secreted. Immune cells modified with the synthetic cytokine signaling system can display a variety of improved characteristics compared with unmodified immune cells, such as the zero or reduced dependency on IL2 when cultured in vitro, enhanced activation upon antigen stimulation, increased cytotoxicity against target cells, and more preferred migration to tumors and improved tumor control capacity when transferred in vivo.

Provided is an engineered TGFβ receptor system to be expressed in immune cells (e.g., T cells) that is repurposed, upon TGFβ binding, to transduce immunosupportive interleukin 9 (IL-9) signaling rather than the usual immunosuppressive TGFβ signaling mediated by endogenous TGFβ receptors expressed in the immune cells. The engineered TGFβ receptor system includes two engineered chimeric TGFβ receptor chains, with their extracellular portions respectively encoding the extracellular domains of TGFβR1 and TGFβR2, and their intracellular portions respectively encoding the intracellular domains of IL9R and IL2γ. T cells modified with such engineered TGFβ receptor system exhibit strong JAK-STAT signaling, and high survival and proliferation capacity upon TGFβ stimulation, especially under repeated antigen stimulation. Such engineered immune cells are expected to have an enhanced persistence and improved control in treating solid tumors which is commonly characterized to have a TGFβ-enrich immunosuppressive environment.

The invention provides a monoclonal antibody of immunoglobulin A. The monoclonal antibody is a monoclonal antibody of specific immunoglobulin A secreted by a mouse anti-human immunoglobulin A monoclonal antibody hybridoma cell line 5F5A4F3 strain, can be used for quantitatively detecting the concentration of RBD-IgA generated by stimulation of a specific antigen, and also can be used for quantitatively detecting the concentration of the immunoglobulin A. The immunoglobulin A monoclonal antibody can be used for detecting the immunoglobulin A monoclonal antibody, can also be used for quantitatively detecting the concentration of total IgA generated by mucosal immunity, and is good in linearity, high in sensitivity, strong in specificity, suitable for evaluating the immune effect of vaccines, and also suitable for screening and monitoring the IgA antibody level in large-scale people.

Compositions for the treatment of cancer that include CAR T cells in which expression of FOXO3 expression is silenced are disclosed in various aspects. In various other aspects, methods for preventing or delaying a development of dysfunction in a CAR T cell associated with chronic antigen stimulation are described that include silencing the expression of FOXO3 by the CAR T cell.

The present disclosure provides inducible constructs comprising transcription initiation and / or transcriptional regulatory elements. These constructs can be used to drive gene expression in response to specific cellular conditions (e.g., in the context of antigenic stimulation). In some embodiments, the constructs are incorporated as part of regulatory circuits useful for controlling the expression and regulation of cells expressing the engineered receptor.

A synthetic cytokine signaling system includes an engineered cytokine signaling chain encoding a transmembrane polypeptide that contains a particular variant intracellular domain of IL9R and an extracellular domain of a cytokine receptor such as IL2Rβ, IL4Rα, IL7Rα, IL9R, and IL21R. Depending on whether a functionally compatible cytokine ligand domain is fused on the N-terminus, the engineered cytokine signaling chain may be in a self-activating form, or optionally may be in a non-self-activating form. In the latter case, the synthetic cytokine signaling system may further include an engineered cytokine ligand chain encoding a corresponding cytokine ligand that can be membrane-bound or secreted. Immune cells modified with the synthetic cytokine signaling system displays improved characteristics compared with unmodified immune cells, such as the zero or reduced dependency on IL-2 when cultured in vitro, enhanced activation upon antigen stimulation, increased cytotoxicity against target cells, and improved tumor control capacity when transferred in vivo.

The present invention provides an influenza granule for poultry and a preparation method thereof, belonging to the technical field of poultry medicines. After carboxylating multi-walled carbon nanotubes, they are compounded with the composite selenium / germanium polysaccharide obtained by fermenting Flammulina velutipes, Lentinula edodes, Grifola frondosa, and Nostoc commune Vaucher, to prepare a polysaccharide-compounded carbon nanotube. Additionally, the obtained composite selenium / germanium protein is coupled with citric acid and cecropin, complexed with bismuth salts, and then compounded with the polysaccharide-compounded carbon nanotube to prepare the influenza granule for poultry. The influenza granule for poultry prepared by the present invention has high bioavailability, good safety, low cytotoxicity, can effectively inhibit virus replication, reduce the viral load, relieve the symptoms caused by the virus, enhance the immune function of the body, and when used together with an immunogen or a vaccine, can assist the antigen to stimulate the body to produce an immune response and improve the antibody expression level, having broad application prospects.

The invention provides a drug-loaded group B neisseria meningitidis and a preparation method and application of a vaccine thereof. The preparation method comprises the following steps: (1) co-incubating attenuated group B neisseria meningitidis by using sulfonated NHS-biotin to obtain biotinylated attenuated group B neisseria meningitidis; (2) after the Pam3CSK4 and the MDP are respectively coupled with the BSA (bovine serum albumin), the Pam3CSK4 and the MDP are respectively coupled with the streptavidin, so that a Pam3CSK4-BSA-streptavidin conjugate and an MDP-BSA-streptavidin conjugate are obtained; and (3) carrying out mixed incubation on the biotinylated attenuated group B neisseria meningitidis, the Pam3CSK4-BSA-streptavidin conjugate and the MDP-streptavidin conjugate, so as to obtain the drug-loaded group B neisseria meningitidis. According to the invention, a remarkable synergistic interaction effect is generated in the aspect of an antigen stimulation effect, the defect of weak immunogenicity of attenuated group B neisseria meningitidis is overcome, and the application prospect is relatively good.

The invention belongs to the technical field of tumor immunotherapy, and particularly relates to an anti-mesothelin antibody and application thereof.Three high-affinity murine antibodies are found and subjected to humanized treatment; the affinity is obviously higher than that of an SS1 antibody. Second-generation CAR-T cells based on the antibody are constructed on the basis, the in-vitro killing effect is better than that of traditional SS1 CAR-T, the CAR-T cells in a humanized form have the tumor cell killing capacity equivalent to that of a mouse source, and meanwhile the cell depletion level within 0-14 days under antigen stimulation is remarkably reduced. The chimeric antigen receptor T cell disclosed by the invention has very strong killing activity on mesothelin positive tumor cells, does not have immunogenicity by using a fully humanized antibody as scfv, and can be repeatedly administrated to enhance the treatment effect of the CAR-T cell.

The invention relates to an IgG4 antibody specifically combined with dermatophagoides pteronyssinus extract and a preparation method thereof. The screening method comprises the following steps: 1) stimulating a lymph node organ with an antigen; 2) analyzing the stimulated lymph node organoid by combining single cell sequencing and an immune repertoire, and screening a potential IgG4 sequence; (3) preparing the potential IgG4 sequence into potential antibody protein in an in-vitro expression manner; and 4) respectively carrying out ELISA detection and biological layer interference technology verification on the potential antibody protein, wherein the antibody which can be specifically combined with the antigen is the IgG4 antibody. An antigen binding fragment of the obtained IgG4 antibody is formed by connecting a heavy chain fragment and a light chain through a disulfide bond, the nucleotide sequence of the heavy chain fragment is shown as any one of SEQ ID No: 1 to SEQ ID No: 3, and the nucleotide sequence of the light chain is shown as any one of SEQ ID No: 4 to SEQ ID No: 6.

The invention discloses application of a taste sense 2 receptor member 31 (TAS2R31) as a knockout target in cellular immunotherapy, and belongs to the technical field of biological medicines. Specifically, it is found for the first time that the proliferation capacity of tumor infiltrating lymphocytes (TIL cells) obtained after TAS2R31 gene is knocked out is remarkably improved, the killing capacity is remarkably enhanced, and the cell phenotype can be converted towards the direction more beneficial to anti-tumor immunity; meanwhile, the TIL cells with the TAS2R31 gene knocked out can release functional cell factors after being stimulated by antigens, and the TIL cells have definite anti-tumor immunocompetence. Therefore, the TAS2R31 is used as a new knockout target and is used for developing a new tumor treatment scheme based on TIL cells or TCR-T cells. The cell therapy provided by the invention provides a new strategy direction for tumor treatment by improving the multiplication capacity and the immune function of the TIL cells and the TCR-T cells.

Disclosed herein are exogenous antigen sensitized immature dendritic cells. The dendritic cell may also be dead. The exogenous antigen sensitized immature dendritic cells may be used to elicit an increased immune response. Further provided are vaccines comprising the exogenous antigen sensitized immature dendritic cells, methods, of inducing an immune response in a patient, and methods of treating a disease.

The loss and / or dilution of one or more antibodies of interest, or part of an antibody, or defocusing, during antigen-related steps for: - immunization of B-cell stimulation, - selection of antibodies or antibody-producing cells, - isolation of antibodies or antibody-producing cells, - and antibody production, remains a limiting factor in antibody production technologies. To improve the focus of immunization and / or selection and / or isolation and / or production of one or more monoclonal or pseudomonoclonal antibodies (different antibodies directed against the same epitope), or of any part of one or more monoclonal or pseudomonoclonal antibodies recognizing an antigen of interest, we propose a versatile immunization and selection support and a new process using this support for the production of monoclonal and pseudomonoclonal antibodies.This versatile immunization and selection support comprises an SP3 diamond carbon phase that binds antigens, such that the bond between the support and the antigen is covalent, preferably a carbon-to-carbon bond between a carbon of the diamond phase and a carbon of the antigen. The diamond support is only weakly immunogenic; since the antigens are bound by a carbon-to-carbon bond (non-peptide or otherwise), the immune response is focused solely on the antigen. This support also improves antibody collection methods, particularly for phage display technologies.

The CD28 costimulatory role becomes particularly manifest under the poorly inflammatory conditions often encountered in tumor draining lymph nodes and the tumor microenvironment. Anti-tumoral T cell responses have thus a great reliance on CD28 signalling. The possibility of inducing high potential antitumor CAR-T cell responses independently of CD28 pathway engagement by CD80 and CD86 represents thus an appealing approach. Now, the inventors surprisingly show that the mere presence in normal T cells of one gain of function mutation at position 538 in the mouse ortholog of the human isoform 3 of Carmil2 does not drive the development of T-cell cancers. The inventors also show that this mutation switches Carmil2 into an activated state which mimics the activated Carmil2 state resulting from physiological CD28 engagement. Therefore, the gain of function mutation can substitute for CD28 engagement and primes the NF-kB signalling pathway for cooperating with the TCR signalling pathway in normal T cells responding in vivo to antigenic stimuli including tumor antigens. Once and only once the TCR has been engaged by an antigen, including a tumor antigen, it permits full T cell activation in absence of co-receptor CD28 engagement. Therefore, rewriting the CD28 costimulatory pathway of CAR-T cells via the introduction of said gain of function mutation in Carmil2 can induce long-lasting anti-tumor T responses in absence of inflammatory cues.

This invention provides an ELISpot kit for detecting T-cell immunity in porcine epidemic diarrhea (PEDD) and its applications, belonging to the field of in vitro diagnostic technology. The hybridoma cell line 6E8-5G5, which secretes anti-porcine interferon-gamma monoclonal antibodies, can be used to prepare high-purity anti-porcine interferon-gamma monoclonal antibodies stably and in large quantities over a long period. Furthermore, an enzyme-linked immunospot (ELISpot) method based on PEDV N protein-specific IFN-γ is established. By detecting the level of specific T-cell immune responses against PEDV N protein after antigen stimulation, this provides technical support for the assessment of cellular immunity after PEDV infection or vaccine immunization.

The application belongs to the technical field of tumor immunotherapy, and particularly relates to an anti-mesothelin antibody and application thereof, and the application finds three mouse-derived antibodies with high affinity, and the antibodies are subjected to humanization treatment; the affinity is significantly higher than that of SS1 antibody. On this basis, a second-generation CAR-T cell based on the above antibody is constructed, and the in-vitro killing effect is better than that of a conventional SS1 CAR-T, and the CAR-T cell in a humanized form has tumor cell killing capacity equivalent to that of a mouse-derived CAR-T cell, and the cell exhaustion level is significantly reduced within a long time of 0-14 days after being stimulated by an antigen. The chimeric antigen receptor T cell has strong killing activity on mesothelin-positive tumor cells, uses a fully human antibody as an scfv, has no immunogenicity, can be repeatedly administered, and enhances the treatment effect of the CAR-T cell.

The invention provides a method for enriching tumor specific cells, and particularly relates to a method for obtaining tumor specific cells aiming at specific tumor species by enriching specific markers. The invention also provides application of the tumor specific cell. The separated immune cells have strong release ability to specific cytokines of lung tumors and cervical tumors, have strong specific killing ability to advanced tumors, or have high expression level of tumor specific recognition markers in a corresponding time window after tumor antigen stimulation. The sorting step reduces the amount of cells required for cell therapy or the in vitro culture time required for cell therapy.