26 results about "FOXP3" patented technology

A method for determining whether a subject is at risk for having a progressing or high-grade pre-invasive lesion, nodule or small mass, or having a solid malignant tumour is described the method comprising: (i) determining a ratio of activated and / or exhausted T cells:naive and / or resting T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence or absence of a panel of biomarkers comprising Ki67 and CD39, or (ii) determining a ratio of activated and / or exhausted T cells:T cells which are not activated and / or exhausted T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence or absence of a panel of biomarkers comprising Ki67 and CD39, (iii) determining a proportion of activated and / or exhausted T cells as a percentage of T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence of a panel of biomarkers comprising Ki67 and CD39, and / or (iv) determining a proportion of activated and / or exhausted T cells as a percentage of T cells in a sample of blood obtained from the subject, wherein the T cells are CD4 T cells, and wherein the determining comprises analysing T cells using cytometry to detect the presence of a panel of biomarkers comprising FoxP3.

The present application relates to the medical technical field, especially to the application of FYB1 gene as a marker in preparation of gastric cancer diagnosis or prognosis judging reagent. The present application research finds that FYB1 gene is highly expressed in gastric cancer tissue and negatively correlated with the prognosis of patients, and can be used as a gastric cancer marker for gastric cancer detection and efficacy evaluation. In addition, FYB1 is positively correlated with the expression of Treg cell marker FOXP3 and co-localized in tissues, suggesting that FYB1 may promote gastric cancer tumor immune escape; the expression of FYB1 gene can significantly inhibit the proliferation, migration and invasion ability of gastric cancer cells, and inhibit tumor growth, indicating that FYB1 gene can be used as a gastric cancer treatment target and play an important role in the treatment of gastric cancer patients.

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.

This application discloses an IL-2 variant fusion protein and its applications. The IL-2 variant fusion protein of this application comprises 1) wild-type hIL-2 or an hIL-2 mutant protein, 2) an hIgG1-HC-Fc mutant fragment, and 3) an hIgG1-LC fragment; the hIL-2 mutant protein is obtained by an N88D mutation in wild-type hIL-2; the hIgG1-HC-Fc mutant fragment is obtained by L236A, L237A, and P331G mutations in wild-type hIgG1-HC-Fc. This IL-2 variant fusion protein, as a novel drug, can regulate Tregs (Foxp3). + ), treatment for Tregs (Foxp3) + This is associated with various refractory autoimmune diseases and inflammation, and prolongs the duration of Tregs (Foxp3). + Related health and lifespan span.

Compositions and methods are described herein that are useful for the detection of prostate cancer progression by determining the expression levels of genes associated with metastatic PCa. Based on the expression of IL-6, SELE, FOSB, NRK, NFRB2, FOXP3, ARG1, CEBPDP, TNFα, ADAMTS4, PENK, FOSL1, DUSP1, ACTA1, AGT, ATF3, CDK1, CXCL8, SELP, VCAN, TFP12, or NR4A3 genes or any combination thereof, treatment of PCa with SELE agonists, TNFα antagonists, and / or immune checkpoint inhibitors (ICIs) are shown to be effective.

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

The invention belongs to the technical field of biological medicine, provides a mustard gas immunotoxicity evaluation method based on Foxp3 promoter methylation, and evaluates the application effect of the Foxp3 promoter methylation level in mustard gas immunotoxicity evaluation in combination with in-vitro cell experiments and in-vivo animal experiments. Results show that Treg cell deficiency is a main reason for tissue damage and inflammation caused by mustard gas poisoning, cell fate and functions of the Treg cell deficiency are mainly regulated and controlled by Foxp3 transcription factors, mustard gas can cause increase of the DNA methylation level of Foxp3 gene loci, DNA hypermethylation of Foxp3 promoters is crucial to Treg cell differentiation inhibition, Th17 / Treg imbalance and systemic inflammation caused by mustard gas exposure, and the Treg cell deficiency is a main reason for tissue damage and inflammation caused by mustard gas poisoning. The methylation level of the Foxp3 promoter can be used as a marker of a mustard gas immunotoxicity evaluation method.

The invention relates to the technical field of cellular immunotherapy, and discloses an application of a CD74 positive regulatory T cell in treatment of graft versus host disease, the CD74 positive regulatory T cell is composed of the following components in proportion: in a sorted and purified cell population, the proportion of regulatory T cells with CD4 + CD25 + CD127-phenotype is 85-95%, the proportion of regulatory T cells with CD25 + CD127-phenotype is 1-5%, and the proportion of regulatory T cells with CD24 + CD25 + CD127-phenotype is 1-5%. Wherein the CD74 high-expression subgroup accounts for 60-75% of the total amount of the regulatory T cell, the cell subgroup functional immune molecule combination comprises CTLA4, FOXP3, TIGIT and TNFRSF18, when the CD74 positive regulatory T cell is used for treating graft versus host disease, the CD74 positive regulatory T cell is firstly used for preventive infusion, single infusion is performed on the day of transplantation, the dosage is 5 * 10 < 5 > cells / receptor, and then the CD74 positive regulatory T cell is used for treating the graft versus host disease. The CD74 positive regulatory T cells are used for repeated therapeutic infusion when early aGVHD symptoms occur, graded treatment is carried out, pathological immune response is inhibited to the maximum extent, immune tolerance is promoted, the treatment is carried out once a week and 2-3 times in total, and the dosage of each time is 1 * 10 < 6 > cells / receptor.

The invention discloses application of timosaponin AIII in preparation of a curative effect enhancer for CAR-T cell therapy and a product for overcoming drug resistance. The invention proves that TAIII is an allosteric inhibitor of an adenosine A2A receptor, and blocks a downstream signal channel through allosteric combination with A2AR, so that expression of a transcription factor FoxP3 is inhibited, Tregs in a CAR-T product is selectively cleared, immunosuppression of the Tregs on effector T cells is relieved, meanwhile, the proportion of central memory T cells is increased, and amplification, durability and cytokine secretion functions of the CAR-T cells are enhanced. The invention further provides a CAR-T cell composition containing the TAIII, and the TAIII and the CAR-T cells are combined or used as a pretreatment agent, so that the tumor removal capability can be remarkably enhanced, and recurrence after treatment can be effectively prevented. The invention provides a safe and effective new strategy for enhancing the anti-tumor activity of the CAR-T cells and overcoming the drug resistance of the CAR-T therapy.

The invention discloses a preparation method and application of a mesenchymal stem cell exosome which is enriched with Foxp1 protein and has immune organ targeting property. The method comprises the following steps: acquiring a single-cell suspension of the mesenchymal stem cells, performing suspension culture on the single-cell suspension of the mesenchymal stem cells in an exosome removal culture medium to induce the mesenchymal stem cells to aggregate to form a compact cell cluster, and then collecting the exosome through differential centrifugation. According to the method disclosed by the invention, the mesenchymal stem cells are induced to aggregate through a suspension culture technology, so that the exosome with high yield and immune targeting is obtained. The Foxp1 protein is specifically enriched in the exosome, the exosome has the characteristics of high yield, immune organ targeting and strong immune regulation capability, Treg cell differentiation is regulated through the Foxp1 / STAT5 / Foxp3 axis, the limitation in the application of the existing exosome is solved, and a new strategy is provided for the treatment of autoimmune diseases.

Methods, polynucleotides, and compositions for generating engineered Treg cells are provided. The methods, polynucleotides, and compositions enable the reprogramming of hematopoietic cells into Treg cells by constitutive or controlled expression of FOXP3 in engineered cells, so that engineered Treg cells can suppress the activation and proliferation of responder T cells.

The described technology pertains to biotechnology, specifically methods and systems for modulating FOXP3 expression in human CD4+ T cells using CRISPR-based genomic editing techniques. FOXP3, a transcription factor essential for regulatory T cell (Treg) function, is constitutively expressed in Tregs but transiently expressed in conventional CD4+ T cells (Tconvs) upon activation. The approach addresses challenges in precise modulation of FOXP3 expression by identifying cis-regulatory elements, such as CNSO, NCNS, and PPP, and trans-regulatory factors, including GATA3, STAT5, and ETS1, that influence FOXP3 expression in Tconvs. Utilizing CRISPR interference (CRISPRi) and CRISPR nuclease (CRISPRn) screens, the methods enable targeted, cell-type-specific modulation of FOXP3 levels. Applications include engineered T cell therapies for autoimmune diseases, cancer, and transplantation. Advanced epigenetic editing tools, such as CRISPRoff, further enhance specificity by targeting DNA methylation states at regulatory loci. This approach offers scalable solutions for programming FOXP3 expression in diverse therapeutic contexts.

The present invention relates to universal immunomodulatory T cells comprising a chimeric antigen receptor and uses thereof and, specifically, to universal immunomodulatory T cells in which immunogenicity of cells is removed so that general T cells obtainable in sufficient numbers from healthy people can be applied to all organ transplant patients and in which Foxp3 and a chimeric antigen receptor are both introduced, and a use thereof.

An expression construct, a nucleic acid or vector or cell comprising said expression construct, and various uses of said expression construct, nucleic acid, vector or cell is disclosed herein. Particularly, an expression construct comprising a PGK promoter operably linked to (i) a first nucleotide sequence encoding a chimeric antigen receptor (CAR), and (ii) a second nucleotide sequence encoding a FOXP3 polypeptide, wherein the first nucleotide sequence is located upstream of the second nucleotide sequence, is provided.

The application provides a kind of marker for predicting the curative effect of lung cancer immunotherapy and the construction method of scoring system, and relates to the field of biotechnology.The inventors have found that the mRNA of CypB, the RNA transcribed by FAM83H-AS1 gene and LncRNA VPS9D1-AS1 are related to the prognosis of lung cancer, and the immune cell infiltration around lung cancer lesions is related to the treatment of lung cancer patients.Accordingly, the application takes the mRNA of CypB, the RNA transcribed by FAM83H-AS1 gene, LncRNA VPS9D1-AS1, panCK, CD3, CD4, CD8 and Foxp3 as markers, and provides a construction method of scoring system for predicting the curative effect of lung cancer immunotherapy.The scoring system constructed by the method can comprehensively evaluate the state of tumor and its microenvironment, accurately predict the progression risk and prognosis of lung cancer, and better guide clinical medication.

The invention provides methods of isolating CD127lo / − immunosuppressive regulatory T cells which can be greatly enriched for FoxP3, methods of expanding the isolated cells, pharmaceutical compositions of such cells, and methods of their use in the treatment of autoimmune and other immune system mediated disorders.

Expression cassettes comprising FOXP3 proteins, chimeric receptors, and / or cell surface receptors are provided. Also provided herein are Treg cells comprising the expression cassettes and methods of use.

A method for generating immuno-free and stress-resistant donor cells comprising editing PRDM1 and FOXP3 genes in T-cells and B-cells with CRISPR-Cas9 and modulating immune responses to reduce inflammation and prevent autoimmunity. Particularly, the present invention discloses a method for treating Type 1 Diabetes, comprising genetically modifying pancreatic beta cells with CRISPR-Cas9, and altering HLA expression, and upregulating immune checkpoint molecules such as PD-L1 to obtain immune-tolerant and stress-resistant pancreatic beta cells.

This invention discloses the application of lupinone in the preparation of drugs for treating psoriasis, belonging to the field of pharmaceutical technology. In this invention, lupinone is used to treat psoriasis by regulating CD4 levels in psoriasis patients. + FoxP3 + The number of Tregs, regulatory T lymphocytes, reduces the expression of CD3-positive cells and the level of inflammatory factors in the skin lesions of psoriasis patients, thereby regulating the immune response of psoriasis patients and thus achieving the treatment of psoriasis. Specifically, it can reduce the severity of psoriasis, improve the degree of erythema, scaling and infiltration of skin lesions, significantly reduce the PASI (Psoriasis Area and Severity Index) score of skin lesions, reduce the thickness of the epidermis at the skin lesion site and inhibit epidermal proliferation, improve hyperkeratosis and parakeratosis, and improve acanthosis.

The application discloses a prognosis prediction system and a prognosis prediction chip for head and neck squamous cell carcinoma, wherein the prognosis prediction chip is a gene expression profile chip for detecting the expression amounts of nine genes AHCTF1, AICDA, BRD8, BRWD3, FOXP3, HNF1A, IKZF3, KDM5A and DC1 of a human. The application obtains nine chromatin regulators most related to the prognosis of the head and neck squamous cell carcinoma through analysis, and the corresponding prediction system can predict the prognosis of the head and neck squamous cell carcinoma patient according to the expression amounts of the nine chromatin regulators, has strong robustness and can greatly improve the prediction accuracy of the overall survival rate of the head and neck squamous cell carcinoma.

The application discloses an immune biomarker combination based on CD8 / FOXP3 and PD-1 and PD-L1 and clinical application thereof. The application utilizes advanced multi-marker immunofluorescence (mIHC) detection and artificial intelligence analysis means to effectively combine and calculate four key immune markers, including immune checkpoint molecules PD-1 and PD-L1, anti-tumor T cell marker CD8 and immune inhibitory Treg marker FOXP3, and the expression of the four key immune markers in the special area of tumor tissues is used to guide clinical practice. The application has the advantages that a new effective combination detection and analysis method of key immune markers for predicting the prognosis of lung cancer patients is provided, and patients are stratified, which has potential value for guiding anti-PD-1 / PD-L1 treatment or Treg cell targeted treatment.

The present invention relates to agents, uses and methods for treating cancer using agents for inhibiting IRF5 expression. Synergistic therapies include agents, uses, and methods for treating cancer using agents for inhibiting IRF5 expression in combination with agents for inhibiting TGF-beta2 expression. In some embodiments, one or more biomarkers, including one or more of IFNGR2, JAK1, and STAT1, and TGF-beta 2 and IRF5, TLR9, FOXP3, CCL22, CREB5, CD8a, CD86, CC14, CD163, ITGAX, and CD11c, can be used to select a subject that can benefit from the method, agent, or use. The agents and compositions may be used in combination with chemotherapy and other standard care therapies.

To provide cells that are competitive against cancer cells without starving or becoming exhausted even in glucose-depleted environments. To provide cells that are effective in metabolic (e.g., low glucose, high lactate, high fatty acid) and immunological tumor environments (e.g., chemokine profiles that induce immunosuppressive immune cells, expression of checkpoint molecules, and infiltration of suppressor cells that negatively regulate anti-tumor immune responses, such as inhibitory cytokines and Treg cells) in which normal T cells or conventional genetically modified cells are inhibited from infiltrating and, even if they infiltrate, are unable to exert long-term effector function due to starvation or exhaustion. [Solution] T cells with effector function, which have been modified to express Foxp3 (including mutant and partially deleted forms) and / or have enhanced Foxp3 expression.

This invention discloses a novel CD8 + T cells and CD4 + T cell subsets. The CD8... + T cell subsets include: subsets characteristically expressing GZMK and PDCD1; subsets characteristically expressing GZMK, GPR183, IL7R, and ZNF683; subsets characteristically expressing GZMK and CXCL13; subsets characteristically expressing GZMK and ZNF683; and subsets expressing at least one of the following KIR genes: KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, and KIR3DL3. The CD4+... + T cell subsets include: subsets that characteristically express FOXP3, TNFRSF9, and CTLA4; and subsets that characteristically express FOXP3 and BACH1.

This disclosure provides isolated antibodies that specifically bind to the C-C Motif Chemokine Receptor 8 (CCR8) expressed on the surface of a cell and exhibit various functional properties, including properties that are desirable in a diagnostic antibody. These properties include binding with high affinity and specificity to CCR8-expressing cells, such as tumor-infiltrating, activated CD4+FOXP3high Tregs, and binding to a human CCR8 (hCCR8) epitope outside the N-terminal domain of hCCR8 to which most therapeutic anti-CCR8 antibodies bind.

Provided herein are peptide-based therapeutics that target POXP3 and methods of use thereof to decrease the immunosuppressive effects of Tregs and inhibit immune dysregulation, while sparring inhibition of activated cytotoxic T cells, for example, in the context of anti-tumor immune responses, autoimmunity, inflammatory conditions, etc.