16 results about "NFAT" patented technology

This invention discloses the application of TRIM29 in breast cancer immunotherapy. The inventors discovered that TRIM29 binds to the voltage-dependent anion channel protein VDAC1 in the outer mitochondrial membrane, regulating the opening of the mitochondrial membrane permeability transition pore, leading to mitochondrial calcium efflux, increased cytoplasmic calcium levels, and activation of the transcription factor NFAT, thereby upregulating PD-L1 expression. Interfering with TRIM29 expression downregulates PD-L1 expression. In breast cancer cells, knocking down TRIM29 significantly downregulates PD-L1 levels in tumor cells, activating T cells to recognize and kill tumor cells.

The present application relates to a marker IBSP of lung cancer bone metastasis and application thereof. Specifically, the present inventors found that IBSP is highly expressed in both plasma and bone metastasis foci of lung cancer patients, and positively correlates with bone metastasis, thus can be used as a biomarker for detecting and diagnosing bone metastasis. Further studies have proved that the differentiation of macrophages to osteoclasts induced by IBSP is a necessary and sufficient condition for promoting lung cancer bone metastasis, thus IBSP inhibitors can inhibit bone metastasis. In addition, the present inventors first found that IBSP can directly induce the positive differentiation of macrophages to osteoclasts by regulating the Rac1-NFAT signaling pathway, thus inhibiting Rac1 can block the lung cancer bone metastasis induced by IBSP. The present application provides an effective target for diagnosing and treating lung cancer bone metastasis, and provides a new method for the prevention, diagnosis and treatment of bone metastasis.

The application discloses application of pulegone as an effective component in an immunosuppressant, and the pulegone with significant calcineurin (CN) inhibiting activity is screened from the Schleichera oleosa Kurz, the immunosuppressive effect of the pulegone is equivalent to that of cyclosporine A which is widely used in clinic, mechanism research shows that the pulegone targets CN / NFAT signal path to play the immunosuppressive activity, and the pulegone has very weak cytotoxicity to spleen cells, and is a high-efficiency and low-toxicity immunosuppressant.

The invention relates to genetic engineering and medicine, in particular to application of rhodinine in preparation of T cell activation drugs. The invention provides an application of rhodinine in preparation of a medicine of a T cell activator. The method comprises the following steps: detecting the GFP fluorescence intensity of the NFAT-GFP report Jurkat T by using an InucyteSX5 high-throughput living cell analyzer, screening an immune activator from a natural compound library, detecting the NFAT-GFP report Jurkat T by using the Inucyte high-throughput living cell analyzer, and carrying out secondary screening, so as to obtain the rose tree alkali capable of effectively activating T cells. According to the present invention, the T cell activation performance of the rhodinine is verified through the research on the activation of the NFAT transcription factor by the rhodinine and the research on the influence of the rhodinine on the expression of the CD25 on the surface of the NFAT-GFP report Jurkat T cell;

Provided herein are nucleic acid constructs comprising one or more Nuclear Factor of Activated T-cells (NFAT) response elements and an expressible nucleic acid sequence encoding a first engineered polypeptide monomer, wherein the first engineered polypeptide monomer comprises a regulatable polypeptide payload and at least one drug response domain (DRD). The abundance, availability, and / or biological activity of the payload is regulated by interaction of an effective amount of an immune cell stimulator with the one or more NFAT response elements and by interaction of an effective amount of a ligand with the one or more DRDs.

Nucleic acid constructs comprising one or more activated T-cell nuclear factor (ATNF) response elements and an expressible nucleic acid sequence encoding a first manipulated polypeptide monomer are provided herein, wherein the first manipulated polypeptide monomer comprises a tunable polypeptide payload and at least one drug-sensitive domain (DSD). The abundance, availability, and / or biological activity of the payload are regulated by the interaction of an effective amount of immune cell-stimulating agent with the one or more ATNF response elements and by the interaction of an effective amount of ligand with the one or more DSDs.

The present invention relates to methods for modulating NFAT activity and / or restoring the suppressed Nuclear Factor of Activated T-cells (NFAT) activity in T cells of a subject in need thereof. In another aspect, the invention provides different herbal compositions for modulating NFAT activity in T cells of a subject in need thereof.

The present disclosure is directed to systems for inhibiting NFAT and / or NFkB signaling to improve the function of CAR expressing immune cells, e.g., CAR T cells. The system enables generation of immune cells engineered to express a CAR or multiple combinations of CARs (multi-CAR) and inhibitors of NFAT and / or NFkB signaling.

The invention discloses a method for constructing CAR-T cells based on tumor tissue infiltration B cells and application. The method comprises the following steps: S1, obtaining tumor infiltration B cells; s2, performing single cell sequencing and BCR sequence analysis on the tumor infiltrating B cells, and screening out a first BCR sequence; s3, constructing an organ-like model; s4, a Jurkat-NFAT report cell line is constructed; s5, constructing a CAR (Chimeric Antigen Receptor)-Jurkat-NFAT report cell line library; s6, co-culturing the report cell line library and the organoid model, and screening to obtain a second BCR sequence; s7, screening out a third BCR sequence capable of specifically recognizing tumor tissues; and S8, constructing the third BCR sequence into a CAR structure, transfecting the CAR structure into a T cell to prepare a CAR-T cell, and co-culturing the CAR-T cell and the organoid to verify the killing function of the CAR-T cell. According to the method, the individualized accuracy of the CAR-T cells is improved, meanwhile, the screening process is optimized, clinical transformation is accelerated, the off-target toxicity risk is reduced, and the method has high patent value and industrialization prospects.

The present disclosure relates, in part, to improved therapeutic cells (e.g., comprising immune cells, such as T cells, e.g., human T cells) that encode or express: a collagen-binding payload; and a target-binding protein (e.g., a CAR, a TCR, a scTCR, a TruC, a TCR / CAR, a synNotch receptor, an IFP, or a multispecific T cell engager). In some embodiments, a collagen-binding payload molecule comprises a cytokine, a toxin, a polypeptide that inhibits an interaction between two or more proteins, an antibody or antigen-binding portion thereof, or a combination of any two or more of the foregoing. In certain embodiments, a collagen-binding payload comprises a cytokine (e.g., a human cytokine), such as a proinflammatory cytokine. In some embodiments, the cytokine is an IL-12. In some embodiments (e.g., in a T cell), expression of the collagen-binding payload is driven by binding of NFAT (nuclear factor of activated T cells) to a NFAT binding site (also referred to as NFAT binding motif). In some embodiments, one or more NFAT binding sites are present and can function as a promoter. In some embodiments, an inducible promoter is responsive to NFAT binding to the one or more NFAT binding sites, and the inducible promoter is operably linked to a sequence encoding the collagen-binding payload.

This invention provides a calcineurin B subunit mutant and its application in the preparation of universal immune effector cells. The CNB mutant of this invention can antagonize the blocking of the NFAT signaling pathway by CsA, FK506, or voclosporin; and simultaneously exhibits resistance to CsA, FK506, and voclosporin. Expressing the CNB mutant of this invention into universal immune effector cells, when combined with immunosuppressive drugs to treat tumors or autoimmune diseases, can reduce the activity of the patient's own T cells, thereby avoiding the patient's rejection of heterologous universal immune effector cells and improving the colonization and therapeutic effect of universal immune effector cells in the patient's body. Furthermore, after treatment, the universal immune effector cells can be rejected after the patient's immune system recovers, making the strategy of discontinuing immunotherapy after treatment possible, which can greatly improve the safety of immunotherapy.

A composition may have an adeno-associated virus (AAV) vector containing a nucleic acid sequence encoding NFAT1 (Nuclear Factor of Activated T Cells 1) protein for treatment of osteoarthritis and other joint diseases. The AAV vector may be AAV serotype 5, other AAV serotypes, and AAV subtype variants. The nucleic acid sequence encoding NFAT1 may be constitutively active NF ATI or wild-type NF ATI. The nucleic acid sequence encoding NFAT 1 may comprise a hemagglutinin epitope tag. At least one AAV vector may comprise a viral genome concentration of about 2x1010 viral genomes. The NFAT 1 may be human NFAT1. The NFAT1 may be mouse NFAT1. A pharmaceutical composition may comprise the composition and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be suitable for intra-articular or local tissue injection. The pharmaceutically acceptable carrier may be sterile saline.

Disclosed is a method of providing antigen-reactive lymphocytes comprising: (a) obtaining lymphocytes of an individual wherein the individual carries at least one antigen; (b) establishing a primary culture of lymphocytes; (c) introducing a transient reporter system into the lymphocytes of the primary culture, wherein the reporter system generates a signal upon activating the nuclear translocation of the T cell nuclear factor (NFAT); (d) attacking the lymphocytes with at least one antigen; and (e) screening at least one antigen-reactive lymphocyte from the lymphocytes by detecting the signal. Also disclosed are pharmaceutical compositions comprising amplified antigen-reactive lymphocytes obtained by the method and kits for performing the method.

A virus vector comprises a constitutive promoter, a nucleic acid sequence encoding a chimeric antigen receptor (CAR), an inducible promoter comprising N nuclear factor of activated T-cells (NFAT) binding motifs followed by the minimal human interleukin 2 (IL-2) promoter, and a nucleic acid sequence encoding a Helicobacter pylori neutrophil activating protein (HP-NAP) and / or an immunological equivalent fragment thereof. The virus vector may be provided in a T-cell useful in T-cell immunotherapy. The T-cells have improved effects in immunotherapy including treating, reducing and / or preventing cancer in a patient.

The invention relates to genetic engineering and medicine, in particular to application of rhodinine in preparation of T cell activation drugs. The invention provides an application of rhodinine in preparation of a medicine of a T cell activator. The method comprises the following steps: detecting the GFP fluorescence intensity of the NFAT-GFP report Jurkat T by using an InucyteSX5 high-throughput living cell analyzer, screening an immune activator from a natural compound library, detecting the NFAT-GFP report Jurkat T by using the Inucyte high-throughput living cell analyzer, and carrying out secondary screening, so as to obtain the rose tree alkali capable of effectively activating T cells. According to the present invention, the T cell activation performance of the rhodinine is verified through the research on the activation of the NFAT transcription factor by the rhodinine and the research on the influence of the rhodinine on the expression of the CD25 on the surface of the NFAT-GFP report Jurkat T cell;

The present disclosure relates generally to compositions and methods for improving T cell therapy. In particular, the disclosure provides polypeptides and recombinant nucleic acid constructs and / or recombinant nucleic acids encoding polypeptides having mutations capable of altering T cell signaling, cytokine production, and / or in vivo persistence in tumors of therapeutic T cells comprising the mutation. The T cell signaling can be by NFAT, NF-κB and / or AP-1 pathways. The disclosure also provides vectors and cells including the polypeptides and / or recombinant nucleic acid constructs and / or recombinant nucleic acids of the disclosure as well as methods of preparing a T cell for use in cell therapy, and methods of identifying a mutation useful for improving T cell therapy.