411 results about "T cell" patented technology

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules.The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to pharmaceutical composition comprising these bispecific antigen binding molecules.

This invention discloses a recombinant adenovirus vaccine targeting the Tp0326 antigen and its preparation method, comprising a recombinant adenovirus vector and the Tp0326 antigen expressed therein. The recombinant adenovirus vector uses a replication-defective human adenovirus type 5 (Ad5) as a backbone, inserting the full-length Tp0326 antigen gene of *Treponema pallidum* into the adenovirus shuttle vector pshuttle-IRES-rGFP-1, and obtaining it through homologous recombination with the adenovirus backbone plasmid pAdEasy-1. This invention, using a replication-defective Ad5 as a vector, provides a recombinant adenovirus vaccine with high safety and efficient expression of the full-length Tp0326 antigen. The expressed antigen has a natural conformation, retains the ECL4 immunodominant epitope, and is more likely to induce a specific immune response, resulting in stronger immunogenicity. The preparation method involves constructing a recombinant adenovirus vector through homologous recombination, packaging it in HEK293T cells, and purifying it by CsCl density gradient centrifugation to obtain a high-purity, high-titer recombinant adenovirus vaccine suitable for large-scale production. The recombinant adenovirus vaccine can be administered via intramuscular or intranasal injection.

The present application relates to an anti-CD3 antibody and its application. The present application develops a specific antibody molecule targeting CD3 epsilon chain, which can activate T cells by combining with CD3 epsilon on T cells. A T cell binding protein containing the CD3 antibody is further designed, which can specifically target and bind to CD3 epsilon on the surface of T cells in vivo and in vitro, so as to achieve moderate activation of T cells. The CAR lentivirus containing the T cell binding protein of the present application can induce the generation of CAR-T cells in vitro and in vivo, and the CAR-T cells have good tumor cell killing efficiency.

This invention relates to an anti-FGFR2 / PD-1 bispecific antibody. The anti-FGFR2 / PD-1 bispecific antibody of the present invention comprises a first antigen-binding domain D1 and a second antigen-binding domain D2, where D1 is an anti-FGFR2 antibody or its antigen-binding fragment, and D2 is an anti-PD-1 antibody or its antigen-binding fragment. The anti-FGFR2 / PD-1 bispecific antibody of the present invention exerts an antitumor effect by suppressing the proliferation of FGFR2 target cells, killing target cells through ADCC activity, and simultaneously inhibiting the binding of PD-1 to its ligand, thereby releasing the inhibitory state of T cells.

Disclosed herein are VH-only single domain binders that target claudin 18.2 (CLDN18.2) and chimeric antigen receptors (CARs) that contain the same, engineered T cells containing the CLDN18.2-targeting CARS, and methods of treating cancer (e.g., gastric cancer or pancreatic cancer) using the CAR-T cells.

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 discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

The application provides a preparation method of a multi-layer sandwich type epoxy group modified magnetic microsphere and application thereof. The multi-layer sandwich type epoxy magnetic microsphere prepared by the preparation method provided in the application can realize efficient and accurate cell sorting through coupling of an antibody, is suitable for cell sorting related scenes such as stem cell separation, tumor cell detection, immune cell treatment (such as CAR-T cell preparation) and pathogenic microorganism enrichment, and provides key material support for cell sorting technology in life science research and clinical diagnosis and treatment.

The embodiment of the application discloses a lung adenocarcinoma risk stratification-prognosis model with binary main effect and application, and belongs to the technical field of biomedicine. + Based on the HMGCR expression and CD8 + T cell exhaustion characteristics, combined with weighted gene co-expression network analysis, protein-protein interaction network, univariate Cox regression and LASSO regression algorithm to layer by layer screen marker genes, a lung adenocarcinoma risk stratification-prognosis model containing CCR2, CD5, CXCR6, EAF1, HLA-DMB, HLA-DQA1, IL15RA, IPO7, KHDRBS1 and SLAMF1 is constructed. Further analysis shows that the risk score is an independent prognostic factor for lung adenocarcinoma, which is closely related to tumor immune escape microenvironment and antitumor drug sensitivity, and the risk score- nomogram has excellent prediction performance and clinical practicability. Therefore, the prognosis model provided by the application provides a new strategy for the clinical stratified treatment, patient prognosis judgment and individualized precise diagnosis and treatment of lung adenocarcinoma.

This invention discloses a NK cell culture kit, its culture method, and its application. The kit includes an amplification medium, a high-efficiency induction medium, an NK-A coating solution, an NK-B mixture, and an NK-C mixture. The amplification medium contains basal medium, NAD+, human serum albumin, transferrin, β-glucan, glutathione, β-mercaptoethanol, and linoleic acid. The high-efficiency induction medium, in addition to the amplification medium components, contains soybean peptides, nicotinamide, inulin, and N-acetyl-L-cysteine. The NK-A coating solution contains heparin sodium, monoclonal antibodies, and antibodies. The NK-B mixture contains Inbakicept, IL-2, and IL-15. The NK-C mixture contains linolenic acid, IL-2, and IL-18. The Inbakicept factor in the kit can activate NK cells and enhance their cytotoxicity; linolenic acid can inhibit T cell proliferation, increase NK cell purity, and enhance cell efficacy.

The application discloses a recombinant oncolytic virus targeting CD317 gene and application thereof in anti-tumor, and belongs to the technical field of tumor treatment. The recombinant oncolytic virus comprises a CD317 inhibitor and an oncolytic virus, and is formed by integrating the CD317 inhibitor into the oncolytic virus genome. The CD317 inhibitor is a substance capable of inhibiting CD317 gene expression or targeting degradation of CD317 protein function, and is selected from shRNA or siRNA targeting CD317. The application develops the oncolytic virus targeting knockdown of CD317 expression, inhibits tumor cell proliferation by reducing CD317 expression of tumor cells, reduces PD-L1 expression so as to break the immune escape mechanism, simultaneously enhances the killing sensitivity of tumor cells to CD8+ T cells, forms a synergistic effect with the oncolysis of the oncolytic virus, and the recombinant oncolytic virus has stronger in-vivo anti-tumor activity, thereby providing a new potential scheme for CD317-driven tumor treatment.

This invention discloses an enhanced CAR-T cell (CARTAC) capable of secreting a targeted membrane protein degrader and its applications. While retaining specific killing function, this cell can expand locally in tumors and continuously secrete the bispecific adaptor molecule scTAC. scTAC can recruit E3 ubiquitin ligases, mediate ubiquitination of tumor cell surface membrane proteins (such as PD-L1), and achieve targeted degradation via the lysosomal pathway, effectively reversing the immunosuppressive microenvironment, overcoming antigen heterogeneity, and eliminating antigen-negative tumor cells through the bystander effect. This invention also utilizes the efficient endocytosis properties of EGFR to design scTAC-dual, which can further enhance degradation efficiency. In various lung cancer mouse models, CARTAC-dual exhibited excellent tumor infiltration capacity, low exhaustion levels, and sustained antitumor activity, without systemic toxicity. This invention integrates the targeted killing and protein degradation delivery functions of CAR-T cells, not only enhancing the control effect on solid tumors but also possessing target scalability, making it suitable for the universal upgrading of various CAR-T products.

The application belongs to the technical field of biological medicine, and discloses an in-situ vaccine type mRNA-tLNP preparation for solid tumor treatment and preparation and application thereof. The preparation is designed by double targets, so that CAR-T kills more tumor cells to overcome tumor heterogeneity, changes the tumor immune microenvironment through autocrine fusion proteins (anti-PD-1 scFv and TGFbetaRII, IL-15 and Flt3L, CD40L), promotes T cell proliferation, and recruits and activates dendritic cells, cross-presents new antigens in the tumor local part, and produces in-situ vaccination effects; circular RNA encoding the above proteins is prepared, and the circular RNA is wrapped by lipid nanoparticles modified by CD3 antibodies, so as to be directly delivered to the body, and a significant solid tumor treatment effect is produced.

The present application relates to the technical field of biology and medicine, and particularly relates to a ULBP2 specific chimeric antigen receptor, a CAR-T cell and application thereof. The ULBP2 specific chimeric antigen receptor comprises a ULBP2 antigen binding domain, a transmembrane domain and an intracellular signaling domain, and the ULBP2 antigen binding domain comprises an amino acid sequence as shown in SEQ ID NO: 1. After the ULBP2 specific chimeric antigen receptor is transduced into lymphocytes, the killing ability of the lymphocytes on tumor cells is significantly enhanced, and the lymphocytes have a significant directional killing effect on tumor cells with high expression of ULBP2. The present application also relates to application of the ULBP2 specific CAR-T cell in combination with an anti-PD1 antibody for treating cancer.

Provided are methods for modifying endogenous TCR genes to produce iPSC-derived T cells with antigen- and sequence-specific TCRs. Also provided are genetically engineered iPSCs, genetically engineered T cells, genetically engineering CAR-T cells, and methods of using the same.

The present invention relates to the technical field of immune engineering, and in particular to a CD155-targeting antibody or antigen-binding fragment and a use thereof. The antibody comprises a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 23 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 24, or a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 25 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 26. The antibody has an excellent binding capability with CD155, and CAR-T cells constructed on the basis of the antibody have a significant killing capability against tumor cells expressing CD155, as well as an obvious cellular internalization effect, the capability of promoting the cytotoxic effect of NK cells, and the capability of promoting the phagocytosis effect of macrophages, thereby exhibiting an excellent anti-tumor effect.

The present invention relates to a product derived from allogeneically cultured postnatal thymus tissue for use in a method of inducing thymopoiesis and thereby promoting donor-specific tolerance to an allogeneic solid organ transplant in a recipient requiring a solid organ transplant, such as a heart, lung, liver, or other solid organ or part of a whole solid organ. The product derived from allogeneically cultured postnatal thymus tissue is prepared by subjecting suitable thymus tissue to a conditioning regimen, said conditioning regimen comprising the aseptic processing of the donor thymus tissue in a thymus organ medium and producing sections of donor thymus tissue partially devoid of T cells. The method of preparing the allogeneically cultured postnatal thymus tissue is further disclosed.

The invention discloses an RTN4RL2 monoclonal antibody and an application of the RTN4RL2 monoclonal antibody. The monoclonal antibody provided by the invention can specifically target human RTN4RL2, and amino acid sequences of complementary determining regions CDR1, CDR2 and CDR3 of a heavy chain variable region of the monoclonal antibody are respectively shown as SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3; amino acid sequences of complementary determining regions CDR1 and CDR3 of a light chain variable region are respectively shown as SEQ ID NO: 4 and SEQ ID NO: 5, and an amino acid sequence of a complementary determining region CDR2 is GAT. The monoclonal antibody can specifically bind to RTN4RL2 and has high affinity to RTN4RL2, in addition, T cell proliferation experiments show that the monoclonal antibody has a remarkable blocking effect on the T cell inhibition effect mediated by RTN4RL2, therefore, the monoclonal antibody can activate anti-tumor immune response by blocking the T cell inhibition effect of RTN4RL2, and a wide anti-tumor application prospect is shown.

Provided in the present invention is an isolated recombinant nucleic acid molecule, encoding a chimeric antigen receptor (CAR) polypeptide containing a single-chain antibody (scFv) targeting a B7-H3 polypeptide. Further provided are a recombinant vector containing the recombinant nucleic acid molecule, a recombinant T lymphocyte expressing the CAR polypeptide, a method for preparing the recombinant T lymphocyte, a drug for treating cancers that contains the recombinant nucleic acid molecule, recombinant vector, and recombinant T lymphocyte, and the use of the recombinant nucleic acid molecule, recombinant vector, and recombinant T lymphocyte in the treatment of cancers.

The application belongs to the field of biological medicine, and discloses a drug screening method for promoting tumor neoantigen production. The method comprises the following steps: under the condition of immune activation, a to-be-screened compound is applied to a neoantigen generation defect cell model; indexes such as the expression level of the neoantigen or the neoantigen-MHC complex, the immune checkpoint molecule, the survival state or cytotoxicity of tumor cells, the activation or proliferation ability of immune cells, and the like are detected; and the candidate compound is comprehensively evaluated. The method realizes a three-dimensional integrated evaluation system of "neoantigen induction efficiency-tumor cytotoxicity characteristics-T cell immune activity" for the first time, can high-throughput screen a large-scale compound library, specifically recognizes and evaluates the comprehensive effect of the candidate compound, thereby efficiently discovers a lead drug with the activity of promoting tumor neoantigen production, solves the fundamental defect that the existing screening technology cannot target the evaluation of the neoantigen induction capacity, and provides a universal and expandable screening platform for the development of an immunotherapy sensitizer.

The present invention belongs to the technical field of sensorineural hearing. Provided is the use of SPTBN1 as a target in the treatment of GJB2-related sensorineural hearing loss. The use comprises: the construction of a stably transfected cell line, wherein: HEK293T cells are cultured using a DMEM culture medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a humidified incubator at 37ºC with 95% air and 5% CO2, and when the cells reach 80%-90% confluence, cell passage is performed; IP-MS analysis, wherein: protein complexes are purified using Protein A / G immunoprecipitation magnetic beads, a portion of the extracted proteins is used as input, and then 2 μg of anti-Cx26 antibody is added to the remaining protein extract, same are gently pipetted and mixed, and incubated on a rotating shaker at 4℃ overnight; immunofluorescence observation of the co-localization of Cx26 and SPTBN1, wherein: a stably transfected cell line expressing WT-Cx26 and Mut-Cx26 is constructed; and co-immunoprecipitation (Co-IP) validation, wherein: a stably transfected cell line expressing WT-Cx26 is constructed. The present invention overcomes the limitations of therapeutic methods, such as the relatively low targeting specificity and short therapeutic time windows associated with full-length protein supplementation via gene therapy, thereby providing new insight into GJB2-related hearing loss, and a new target and a new treatment for same.

Provided is a use of mitofusin 2 (MFN2), an MFN2 variant capable of interacting with SERCA2, or an MFN2 expression promoter in maintaining and / or promoting tumor-killing capability and / or viability of a CD8 T cell. Also provided is a use of a CD8 T cell overexpressing MFN2 or a variant thereof for treatment of cancer.

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

The application discloses application of falcarinol-7-methyl ether and derivatives thereof in preparation of medicines and functional foods for delaying aging or immune regulation. In the application, the falcarinol-7-methyl ether and derivatives thereof are derived from falcarinol-7-methyl ether, and can effectively delay replicative senescence of mesenchymal stem cells, inhibit expression of aging-related markers of mouse liver and lung induced by adriamycin, improve grip strength of the mouse, enhance muscle function, and promote proliferation of T cells separated from human peripheral blood mononuclear cells, and have an immune regulation effect. Therefore, the falcarinol-7-methyl ether and derivatives thereof have good effects of improving telomerase activity, anti-aging and immune regulation, and can be developed into anti-aging or immune regulation products.

Bispecific antibody constructs comprising a first binding domain, which binds to human alkaline phosphatase, placental type (ALPP) and / or alkaline phosphatase, germ cell type (ALPPL2), on the surface of a tumor cell and a second binding domain, which binds to human CD3 on the surface of a T cell.

The application belongs to the technical field of tumor immunotherapy, and particularly relates to a composition for enhancing tumor immunogenicity and application thereof. The composition for enhancing tumor immunogenicity comprises, in terms of mass fraction, 10-15 parts of radix stephaniae tetrandrae, 10-20 parts of radix astragali, 3-9 parts of glycyrrhiza uralensis, and 3-12 parts of atractylodes macrocephala. The composition for enhancing tumor immunogenicity provided by the application is a natural traditional Chinese medicine prescription, has good biocompatibility, low toxicity and side effects, and is suitable for long-term treatment. The composition enhances immunogenicity by up-regulating MHC-I expression of tumor cells, activates CD8 + T cell-mediated anti-tumor effect, realizes autologous immunotherapy, and can avoid related side effects of exogenous immunotherapy. The composition can also be used in combination with a PD-1 blocker to synergistically improve anti-tumor efficacy and prolong patient survival.

The present disclosure provides, among other things, a method of isolating and expanding gamma delta (γδ) T cells, wherein the method comprises: (a) isolating non-hematopoeitic tissue by biopsy or explant, and (b) culturing the isolated non-hematopoeitic tissue in the absence of a three-dimensional scaffold or grid, thereby expanding and isolating gamma delta (γδ) T cells.

This invention relates to the field of biotechnology, specifically to a TruC-T cell that secretes and expresses IL-7 and PF4 to enhance anti-tumor activity and targets uPAR, and its application. Interleukin-7 (IL-7) can effectively promote the development, survival, and proliferation of T cells, while platelet factor 4 (PF4 / CXCL4) can regulate the immune response and chemotactically attract leukocytes to specific sites; the synergistic effect of the two can enhance the anti-tumor function and persistence of T cells. Meanwhile, urokinase-type plasminogen activator receptor (uPAR) is highly expressed in various solid tumors and hematological malignancies, making it an ideal target for tumor therapy; TruC-T cells targeting uPAR can precisely act on tumor tissue, and combined with the immune-enhancing effects of IL-7 and PF4, can significantly improve the efficacy of anti-tumor immune responses, prolong the duration of therapeutic effects, and reduce tumor recurrence.

This invention discloses a T-cell training method based on tumor organ-on-a-chip. The method includes: preparing an organ-on-a-chip with a micropillar array and a biomimetic fishbone structure; introducing primary tumor cells from a patient into the chip, causing them to spontaneously form uniform three-dimensional tumor spheroids; dynamically pumping pre-activated peripheral blood lymphocytes from the same patient into the chip and co-culturing them with the tumor spheroids; collecting the co-cultured lymphocytes and repeating the co-culture process multiple times to obtain a lymphocyte population with enhanced anti-tumor activity. This invention utilizes organ-on-a-chip technology to highly simulate the dynamic tumor immune microenvironment in vivo. Through multiple cycles of "training," it effectively activates and expands tumor-specific T cells, avoiding immune exhaustion, and providing a highly efficient and controllable new platform for personalized immunotherapy of solid tumors.