158 results about "Effector cell" patented technology

The purpose of the present invention is to provide: a novel therapeutic or prophylactic agent for xerophthalmia; a therapeutic or prophylactic agent for graft-versus-host disease; a corneal epithelium wound healing promoter; a corneal invasive inflammatory cell inhibitor; or an inhibitor of differentiation of lymphocytes into effector T cells. The present invention provides: a therapeutic or prophylactic agent for xerophthalmia, a therapeutic or prophylactic agent for graft-versus-host disease, a corneal epithelial wound healing promoter, a corneal invasive inflammatory cell inhibitor, a tear amount maintenance agent, a corneal epithelial damage inhibitor, and a method for preparing the same, which comprises, as an active ingredient, a substance derived from a stem cell culture supernatant; a cell proliferation marker positive cell inhibitor, or an inhibitor of differentiation of lymphocytes to effector T cells.

Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen / LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

The present invention relates to antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and / or expand T effector cell populations or function. For example, antibodies of the invention include antagonistic TNFR2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.

Therapeutic use and dosing regimen of anti-ICOS antibodies or antigen-binding fragments thereof for modulating the ratio between regulatory T cells and effector T cells, stimulating the immune system of patients, and / or treating tumours or cancers, as monotherapy or combination therapy, e.g., with anti-PD-L1 antibodies or antigen-binding fragments thereof.

The application provides a nanobody targeting human transmembrane activator and calcium modulator and cyclophilin interactor (TACI) and an application thereof, and the antibody is derived from a llama heavy chain antibody variable region. The anti-TACI single-domain antibody NB38 can specifically bind to human TACI with high affinity, can recognize a recombinant TACI protein, can also recognize a TACI with a natural conformation on a cell surface, and can partially block a BAFF / APRIL signal pathway. Based on the nanobody, the application constructs a fusion protein, a chimeric antigen receptor, an effector cell expressing the chimeric antigen receptor, and a double-specific cell linker and other genetically engineered forms. The nanobody can be further extended into a drug coupling form. The product of the application can be used for mediating directional recognition and killing of TACI positive cells, and can be used as a supplement and expansion of BCMA targeted therapy, and provides a new candidate technical scheme for targeted therapy of multiple myeloma and other TACI related diseases.

GD2 specific chimeric antigen receptor effector cells for the treatment of solid tumors, possibly in combination with an enhancer of a Zeste homolog 2 (EZH2) inhibitor. The invention relates to a GD2-specific chimeric antigen receptor (GD2. CAR) effector cell for use in the treatment of solid tumors, in particular in the treatment of extracranial GD2 + tumors, such as soft tissue sarcoma and osteosarcoma, neuroblastoma, melanoma, lung cancer, bladder cancer and retinoblastoma, and brain tumors. In addition, the present invention also relates to the use of the GD2. CAR genetically modified effector cell in combination with an enhancer of a Zeste homolog 2 (EZH2) inhibitor for the treatment of solid tumors.

Provided herein are multispecific antibodies that selectively bind to PSMA and effector cell antigens such as CD3, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same.

The present invention relates to an anti-GDF15 antibody and to a dosage regimen for the treatment of cancer in a human patient using the anti-GDF15 antibody. The present inventors identified a mechanism by which GDF-15 blocks adhesion and transgression of predominantly T-lymphocytes into tissues. Hence, a novel treatment approach has been established by the present invention that facilitates effector T cell entry into tumor tissue upon blockage of GDF-15 using the antibody of the present invention thereby allowing the treatment of cancer in human patients.

The invention provides an antibody specifically binding to CLL-1 or an antigen binding fragment thereof, a multispecific antigen binding molecule, a chimeric antigen receptor, an immune effector cell, a nucleic acid fragment, a carrier, a host cell, a pharmaceutical composition, a kit, a preparation method and application thereof in disease treatment and CLL-1 detection.

This invention discloses an enhanced TCR and its uses. The enhanced TCR includes an α-chain variable region containing CDR1α, CDR2α, and CDR3α, and a β-chain variable region containing CDR1β, CDR2β, and CDR3β; wherein the enhanced TCR has a T30H mutation relative to the parental TCR's CDR1α, or the enhanced TCR has an S102H or G99H mutation relative to the parental TCR's CDR3α. The enhanced TCR provided by this invention is obtained by mutation based on the parental TCR, possessing a highly sensitive ability to bind target antigen peptides, significantly improving target cell recognition ability, and mediating the specific killing effect of effector cells on antigen-positive target cells, and exhibiting no allogeneic reaction to different HLA subtypes. It can be used to treat various cancers caused by KRAS G12D positivity.

Provided herein are cell-based assays for measuring the immunomodulation of therapeutic biologics using immobilized recombinant proteins. Specifically, the present disclosure relates to a method of assessing and / or determining a biomolecule-induced immune response, comprising: a) immobilizing a recombinant membrane protein or a fragment comprising an extracellular domain thereof on a support; b) contacting the immobilized protein or fragment with (i) a biomolecule, such as an antibody, and (ii) effector cells, and c) detecting activation of the effector cells to assess and / or determine an immune response induced by the biomolecule, such as ADCC, ADCP.

Disclosed herein are polypeptides and polypeptide complexes that are capable of binding tumor cell antigens and effector cell antigens. In some embodiments, the polypeptides and polypeptide complexes bind the tumor cell antigens and the effector cell antigens in a tumor microenvironment.

Provided are a set of fully human TSH receptor (TSHR)-blocking monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and single memory B cells that specifically recognize TSHR in peripheral blood of a patient with a high titer of TSH-blocking antibodies (TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells to perform screening and validation of antibody properties to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully human TSH receptor-blocking monoclonal antibodies specifically bind to a TSHR, and effectively block signal transduction after a TSH binds to a receptor, inhibit the synthetic secretion of thyroid hormones, and significantly reduce and inhibit TSHR expression and fibrosis in orbital fibroblasts of effector cells associated with thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves' disease (GD) and other diseases caused by hyperthyroidism, such as thyroid eye disease (TED).

Provided herein are multispecific antibodies that selectively bind to PSMA and effector cell antigens such as CD3, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same.

The application of raspberry ketone in the immunotherapy of pancreatic cancer belongs to the technical field of biological medicine, and provides the application of raspberry ketone in the immunotherapy of pancreatic cancer. The application discloses that raspberry ketone can specifically and widely up-regulate the expression of MHC-I molecules on the surface of pancreatic cancer cells, and significantly enhances the infiltration and function of anti-tumor effector T cells in the tumor immune microenvironment. In-vivo and in-vitro experiments prove that raspberry ketone can reverse tumor immune escape by up-regulating MHC-I, and after being combined with a PD-1 immune checkpoint inhibitor, the raspberry ketone can produce a significant synergistic anti-tumor effect, significantly inhibit the growth of pancreatic cancer and prolong the survival period of tumor-bearing mice. The application provides a new strategy of combining a natural small molecule immunomodulator with an existing immunotherapy, and provides an innovative solution and a drug candidate for overcoming the difficulty of pancreatic cancer tolerance to immunotherapy.

The invention relates to the field of immune cells. According to the preparation method and application of the novel immune cell, lentivirus containing DNA molecules subjected to gene modification is used for transfecting cells in peripheral blood of mammals, so that the cells can be passaged for multiple times, and the cells have the antigen presenting capacity and the capacity of activating and amplifying natural killer cells. After the cell is further genetically modified, better transmembrane transfer, antigen presentation and natural killer cell activation can be realized. After gene modification, the cell and different cytokines or small molecules jointly activate and amplify mononuclear cells to obtain a larger number of natural killer cells with higher purity, epigenetics are regulated and controlled to change the receptor and ligand expression quantity of the natural killer cells, and then the cytotoxicity of effector cells is improved. The invention can be used for preparing antigen presenting cells and CTL cells aiming at different antigens and an application method. The cells and the using method have wide application prospects in the aspects of prevention and treatment of tumors and infectious diseases.

The invention relates to the technical field of biotechnology and immunotherapy, and discloses a method for inducing and amplifying pMHC specific homologous TSCM, which comprises the following steps: a) preparing pMHC presenting a single antigen peptide; b) sorting lymphocytes and mononuclear cells from a donor, and connecting the pMHC presenting the single antigen peptide obtained in the step a) to the surface of the separated mononuclear cells as stimulating cells; c) co-culturing the sorted lymphocytes serving as effector cells and stimulated cells in a culture medium containing a glycogen synthase kinase-3beta inhibitor, and inducing to generate pMHC specific homogeneous TSCM; and d) separating the pMHC specific homologous TSCM obtained in the step c). The method can induce and amplify sufficient pMHC specific homogeneous TSCM for adoptive immunotherapy, overcomes self tolerance and avoids or alleviates GVHD (Growth Vitamin Horse Disease); the preparation method is simple, induction and amplification efficiency is high, and universality and flexibility are achieved.

The application relates to the technical field of biopharmaceuticals, and discloses a PD-1 and CTLA-4 double-target inhibiting polypeptide or a pharmaceutically acceptable salt thereof and an application thereof, wherein the polypeptide has a structure as shown in formula (I): X1SPILYQMCDYKRX2 (I). The polypeptide or the pharmaceutically acceptable salt thereof can simultaneously produce high-affinity binding to PD-1 and CTLA-4, has excellent biological blocking activity, can significantly improve the proportion of effector T cell subgroups in tumor tissues, and effectively enhances the anti-tumor immune response of the body. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for related detection of PD-1 and CTLA-4, and can be used as a new anti-tumor candidate drug, thereby providing a brand-new treatment scheme for cancer patients.

Provided are a TL1A single-domain antibody and the use thereof. Specifically provided are a single-domain antibody or antigen-binding fragment specifically binding to human TL1A, a multispecific antigen-binding molecule, a chimeric antigen receptor, an immune effector cell, a nucleic acid molecule, a vector, a cell, a preparation method, a pharmaceutical composition, a kit, a pharmaceutical use, and a disease treatment method.

Some aspects relate to engineered cells comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) and at least at first coding exon of a FOXP3 gene, where expression of the CAR and FOXP3 are linked, such that CAR+ cells have a regulatory T cell (Treg) phenotype. Some aspects relate to methods of producing engineered cells in which expression of a CAR and FOXP3 are linked, thereby reducing the incidence of contaminating CAR+ T effector cells. Further aspects relate to methods of screening CARs suitable for expression by a Treg. Some aspects relate to engineered cells expressing an anti-CD19 chimeric antigen receptor (CAR). Some aspects relate to methods of producing engineered cells expressing an anti-CD19 CAR. Some aspects relate to uses of cells expressing anti- CD19 CARs.

The application of poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers in constructing micro / nanocarriers for antitumor drugs belongs to the field of biomedical polymer materials and nanomedicine. The antitumor drugs are small-molecule chemotherapeutic agents, small-molecule photosensitizers, small-molecule immunotherapeutic agents, and small-molecule radiosensitizers. The particle size of the poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers is 10–5000 nm. The effective concentration of the poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers is 1–500 mg / kg. The antitumor mechanism of the poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers includes increasing the activity of effector T cells in the tumor microenvironment and increasing the concentration of cytokines such as IFN-γ at the tumor site. In the field of tumor therapy, PLA and PLGA materials composed of D-lactic acid have shown good effects in inhibiting tumor growth, prolonging the survival period of tumor-bearing mice, and activating antitumor immune responses.

Provided herein are affinity matured anti-galectin-9 (Gal9) antibodies. The antibodies have improved binding affinity to Gal9. Also provided herein are method of use of the affinity matured anti-Gal9 antibodies, including methods of treatment of cancer, methods of rescuing or promoting effector T cell proliferation, methods of enhancing effector T cell activity, and / or of identifying and treating cancer in a subject including the administration of the anti-Gal9 antibodies described herein. Also provided are polynucleotides encoding the heavy chain or the light chain or the antigen-binding portion thereof described herein, and vectors, especially expression vectors, including the polynucleotides described herein.

Disclosed herein is a method for enhancing adoptively transferred autologous or allogeneic immune effector T-cells (including gamma delta T cells (γδ-T cells)) by targeting the thioredoxin (TRX)-interacting protein (TXNIP). In addition, disclosed herein are cDNA sequences for the co-expression of immune receptors (CARs, TCRs, etc) in combination with guide RNAs, and / or artificial or natural microRNAs, and / or shRNAs targeting TXNIP.

This invention discloses a single-cell microarray-based kit and method for in situ quantitative detection of receptor-binding allergen-specific IgE. The kit includes: a single-cell microcavity array chip, an antigen barcode chip, a plastic clamp, IgE standards, fluorescently modified IgE detection antibodies, and auxiliary reagents. During detection, basophil single cells are loaded into the microcavity array chip, lysis buffer is added, and the cells are clamped together with the antigen barcode chip. Low-temperature incubation allows the allergen-specific IgE released from cell lysis to be captured in situ by the antigen on the chip. A sandwich immunoassay is then performed using a fluorescently labeled antibody, and absolute quantification is achieved using a standard curve. This invention is the first to achieve high-throughput, high-sensitivity, multi-component parallel in situ quantitative detection of basophil membrane receptor-binding sIgE at the single-cell level. It can directly reflect the functional sensitization state of effector cells and has advantages such as simple operation, low sample requirement, and no need for complex valve devices.

To provide methods and compositions for obtaining functionally enhanced derivative effector cells obtained from the differentiation of genomically engineered iPSCs.SOLUTION: Derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also there are provided therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.SELECTED DRAWING: Figure 1

The present application relates to the field of environmental monitoring and biosensing technology, and particularly relates to a detection method and system for new pollutants in ecological environment, comprising the following steps: S100: culturing specific effector cells in a biosensing channel, and collecting trans-epithelial electrical resistance (TEER) signals of the effector cells in real time; S200: monitoring a change rate of the TEER signals, and generating an enrichment triggering instruction when the change rate exceeds a preset threshold; S300: in response to the enrichment triggering instruction, introducing a fluid to be tested, which generates the change rate, into a surface-enhanced Raman scattering (SERS) detection cavity, and starting an active enrichment unit to in-situ concentrate the fluid to be tested, so that the volume of the fluid to be tested is contracted to a detection area of a SERS substrate; the present application uses impedance response of effector cells as a preliminary screening "sentinel", realizes targeted capture of only abnormal samples with acute toxicity, avoids ineffective detection of a large number of non-toxic water samples, and significantly improves monitoring efficiency.

The present disclosure provides an autologous cell therapy for treating a cancer. Transarterial tirapazamine embolization (TATE) therapy induces tumor necrosis, which, in combination with anti-PD-1 therapy, enhances the efficacy of anti-PD-1 through TATE-induced expansion of anti-tumor T cells activated by the anti-PD-1 antibody. PBMCs collected from TATE and PD-1 -treated patients for RNA and DNA extraction and next generation sequencing (NGS) analysis of complementarity region-3 of the TCR from T cell populations in the PBMCs show that clonal expansion of anti-tumor specific T cell receptors (TCRs) occurs. Expansion of the PBMC population for administration to a cancer patient preferentially expands the population of effector T cells targeting the tumor cells without a need for genetic manipulation.

To provide a method and composition for generating induced non-pluripotent cells differentiated from single-cell induced iPSC (induced pluripotent stem cell) clone lines. [Solution] A method and composition are provided for obtaining functionally enhanced induced effector cells obtained from targeted differentiation of genome-manipulated iPSCs. The iPSC-induced cells provided herein have stable functional genome editing that results in improved or enhanced therapeutic effects. Therapeutic compositions and their use are also provided, comprising functionally enhanced induced effector cells alone or in combination therapy with antibodies or checkpoint inhibitors.