65 results about "Central Memory T-Cell" patented technology

The present invention belongs to the technical field of cancer immunotherapy, and particularly relates to a cholesterol-modified cationic liposome tumor vaccine, a preparation method therefor, and use thereof. In order to solve the problems of poor targeting and strong side effects of TLR agonists in anti-tumor treatment, the present invention provides a cationic liposome prepared from a cholesterol-modified 1V209 molecule, a cationic lipid component, cholesterol, and DSPE-PEG2000, and then the cationic liposome and ovalbumin 5 form the tumor vaccine by electrostatic adsorption. Animal experiments show that the vaccine can induce antigen-specific CD8+ T cells, activate lymphocytes, and generate stronger antigen cross-presentation, more memory T cells, antibodies, and cytokines. Prophylactic inoculation with the vaccine can significantly delay the progression of mouse melanoma and lymphoma and prolong the survival of mice. The combination use of the vaccine and a PD-1 checkpoint inhibitor can further enhance the anti-tumor effect. Therefore, the vaccine is a promising cancer vaccine.

The invention provides application of a substance for detecting the ratio of lymphocyte subgroups in preparation of a reagent or a kit for diagnosis or auxiliary diagnosis of Graves disease, and belongs to the technical field of preparation of disease diagnosis reagents. A research shows that compared with a healthy sample, the proportion of B cells in a lymphocyte subpopulation of a to-be-detected sample is remarkably increased, the proportion of NK cells is remarkably reduced, the proportion of activated T cells is remarkably reduced, the proportion of memory T cells is remarkably reduced, the proportion of CD4 + memory T cells is remarkably reduced, the proportion of Th1 cells is remarkably reduced, and the proportion of Tc1 cells is remarkably reduced, so that the to-be-detected sample is a GD patient; the substance for detecting the ratio of lymphocyte subgroups is high in sensitivity and specificity when being used for diagnosis or auxiliary diagnosis of Graves disease.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is described. Methods of generating same and using same are also described.

The invention discloses application of cucurbitacine I in preparation of cisplatin sensitization drugs for treating ovarian cancer, and belongs to the technical field of sensitization drugs for tumor chemotherapy. CuI and CDDP have a good synergistic tumor inhibition effect on ovarian cancer, CuI may directly act on EGFR and can be combined with CDDP to significantly inhibit phosphorylation of EGFR and downstream STAT3 protein thereof, induce DNA damage and ROS accumulation, amplify a pyroptosis effect, increase release of TAAs and DAMPs, promote DC maturation and promote infiltration of CD8 + T cells and memory T cells in TIME in vivo, so that the tumor inhibition effect on ovarian cancer is improved. The expression of an inhibitory costimulatory molecule PD-1 in CD8 + T cells is reduced, the whole body immune effect is activated, and the TIME of the ovarian cancer is remarkably improved. The combined treatment strategy of CuI-CDDP controls the progress of ovarian cancer from a dual mechanism of directly inhibiting tumor cells and promoting anti-tumor immune activation.

The present invention relates to a biomarker for diagnosing pediatric atopic dermatitis and use thereof. As result of comparing immune phenotypes of a healthy control group with those of pediatric atopic dermatitis patients, it has been identified that Th1, Th2, Th17 and Th22 cells or expression of STAT1, CD6 and ALCAM genes are increased or decreased. In addition, in the present invention, it has been identified that the frequencies of monocytes, plasmacytoid dendritic cells, CD4 central memory T cells, and CD4 effector memory T cells are related to the severity of pediatric atopic dermatitis. Therefore, the present invention can ensure an efficient treatment strategy for pediatric atopic dermatitis by accurately diagnosing pediatric atopic dermatitis and the severity thereof.

The invention discloses an application of sarcandra glabra polysaccharide in preparation of a medicine for preventing and / or treating psoriasis and delaying relapse of psoriasis. The glabrous sarcandra herb polysaccharide can relieve inflammation caused by psoriasis, reduce expression of memory T cells at skin lesions of a psoriasis recurrence model mouse and relieve psoriasis symptoms of the recurrence model mouse. The invention finds that the glabrous sarcandra herb polysaccharide can obviously improve the skin injury degree of an imiquimod (imiquimod, IMQ) interval induced psoriasis recurrence model mouse, reduce the skin erythema, thickening and scale of the IMQ interval induced psoriasis recurrence model mouse, and reduce the expression of memory T cells at the skin injury part of the psoriasis recurrence model mouse, so that the glabrous sarcandra herb polysaccharide can be used for treating the psoriasis. The glabrous sarcandra herb polysaccharide has great application prospects in preparation of the medicine for preventing / treating the psoriasis, and especially can relieve recurrence symptoms of the psoriasis.

This invention belongs to the field of biomedical technology, specifically relating to a method and application for preparing CAR-T cells with enhanced persistence based on the piggyBac transposon system combined with electroporation. This invention, through specific piggyBac dual plasmid ratios and electroporation conditions, can improve transfection efficiency to over 80%, and the integration site is more likely to be located in a safe genomic region, supporting long-term stable CAR expression. Furthermore, cell expansion kinetics are significantly improved, with expansion exceeding 120-fold within 15 days. The results of the examples show that CAR-T cells prepared using the method described in this invention exhibit significantly enhanced tumor cell killing ability and cytokine secretion levels in in vitro models, and are rich in memory T cell subsets (Tcm / Tem) with greater persistence and self-renewal potential. This indicates that this invention not only changes the method of gene delivery but also shapes the intrinsic properties of cells, enabling them to acquire potentially superior in vivo persistence and long-term anti-tumor capabilities.

The invention discloses PDADMAC modified silicon dioxide mineralized foot-and-mouth disease virus-like particles as well as a preparation method and application thereof. The PDADMAC modified silicon dioxide mineralized foot-and-mouth disease virus-like particle (VLPs-SiO2) is a mineralized particle obtained by forming a silicon dioxide mineralized foot-and-mouth disease virus-like particle under the action of PDADMAC and then further modifying the silicon dioxide mineralized foot-and-mouth disease virus-like particle with PDADMAC, and the SiO2 mineralization rate of FMDV VLPs reaches 90% or above. The observation of a transmission electron microscope and a scanning electron microscope shows that the VLPS-SiO2 is spherical-like nano-particles with the particle size of 80-100 nm. According to the present invention, the level of FMDVVLPs ingestion by DC2.4 cells is increased by SiO2 mineralization, after the mice are immunized by nasal dripping, the specific antibody level in the serum of the VLPS-SiO2 immune group and the secretory IgA level in the lung, the cecum and the excrement are higher than the level of the FMDVVLPs immune group, and the levels of Tfh, Th1, Th2, memory B cells and memory T cells are increased. The invention provides an effective technical means for enhancing mucosal immune protection of the VLPs vaccine.

A culture medium for immune cells and use thereof. The culture medium comprises: 200-1000 U / mL IL-2, 10-100 ng / mL IL-4, 10-100 ng / mL IL-15, 2-20 ng / mL anti-CD3 monoclonal antibody, 2-20 ng / mL anti-CD28 monoclonal antibody, 0.5-20 μM GSK-3β inhibitor, 0.1-10 μM Wnt / β-catenin signaling pathway agonist, 1-10 μg / mL transferrin, 1-10 μg / mL ethanolamine, 1-10 μg / mL water-soluble cholesterol, 1-10 μg / mL insulin, 1-10 mM L-alanyl-L-glutamine, 1-10 μg / mL L-ascorbic acid, 1-10 μg / mL taurine, 0.1-1 μg / mL putrescine, and an RPMI 1640 medium. The culture medium can effectively keep the survival rate of cells, efficiently induce the proliferation of memory T cells, and amplify the number of memory T cells. The culture medium has the advantages of low cell culture cost and good cell quality.

The invention discloses a CD3 antibody-polypeptide, which is characterized in that an amino acid sequence of a light chain variable region of a CD3 antibody is linked with an amino acid sequence of polypeptide through a triple link of a GGGGS flexible joint; and the CD3 antibody-polypeptide can be coupled with the RNP compound through a chemical bond to form the CD3 antibody-polypeptide-RNP compound. The CD3 antibody-polypeptide-RNP compound is used as a delivery system for gene editing in the TILs cells, in the gene editing process, CD3 antibody-polypeptide has good cell penetrability and stability, an exogenous gene can be efficiently and accurately delivered into a double-chain incision manufactured on a TRAC gene of the TILs cells, cell damage caused by electrotransfection is avoided, and the CD3 antibody-polypeptide-RNP compound can be applied to gene editing of the TILs cells. The prepared TI Ls cells have a higher proportion of memory T cells (CD45RO < + > CD62L < + >) and a higher proportion of tumor specific T cells (CD8 < + >), so that the TI Ls cells have a better tumor killing effect.

Provided herein are methods of treating cancer by activating resident memory T cells using one or more antigenic peptides.

The invention provides an FcRn-targeted Brucella multi-epitope nano vaccine, which can realize long-term protection, shows continuous immune memory, has high-frequency hair-growing central B cells (GCB), follicular helper T cells (TFH) and central memory T cells (TCM), and ensures long-term immune surveillance; even six months after immunization, the serum IgG titer is still obviously higher than that of a control group; efficient antigen delivery can be achieved, specifically, a chitosan-based nano-particle system is adopted, and antigen protection and intestinal epithelium uptake are enhanced through FcRn targeted ligand modification; the delivery efficiency can be improved by 10 times, and the gastrointestinal mucosal barrier is overcome; in addition, rapid immune starting can be achieved, multi-dimensional immune response is induced within 14 days after final immunization, and rapid protection is provided for resisting brucella infection.

The invention relates to the technical field of medicines, in particular to a zinc ion polypeptide compound immunologic adjuvant as well as a preparation method and application thereof. The preparation method comprises the following steps: mixing polypeptide, a PBS buffer solution, new coronavirus S protein, a CpG ODN immune activator and zinc ions, and standing to obtain the zinc ion polypeptide compound immunologic adjuvant. A dual-adjuvant system mixed with CpG ODN shows excellent performance in activation of lung tissue immunity, and in the cellular immunity level, the response intensity of CD4 + T and CD8 + T cells is enhanced, and formation of related tissue resident memory T cell phenotypes is promoted; on the humoral immunity level, a Gel (Zn < 2 + >) and CpG ODN dual-adjuvant system obviously stimulates the increase of the number of B cells and the activation, and can effectively stimulate the secretion of a main antibody sIgA for mucosal immunity. On the whole, the dual adjuvants realize the synergistic enhancement of T cell (containing TRM) and B cell immunity.

The invention relates to an anti-CD45RO monoclonal antibody and application thereof in preparation of drugs for treating autoimmune diseases, the anti-CD45RO monoclonal antibody comprises an antibody heavy chain variable region and / or an antibody light chain variable region: a) the antibody heavy chain variable region comprises three complementary determining regions: CDR1, CDR2 and CDR3; and b) an antibody light chain variable region, wherein the antibody light chain variable region comprises complementarity determining regions: L-CDR1, L-CDR2 and L-CDR3. The invention also comprises application of the anti-CD45RO monoclonal antibody in preparation of drugs for treating immune diseases. The monoclonal antibody aiming at the CD45RO can specifically recognize and combine CD45RO molecules on the surfaces of the memory T cells, so that the activation and function of the memory T cells are blocked, and the inflammatory response of immune diseases is reduced by reducing the activity of the memory T cells, so that the symptoms of patients are improved. The compound is expected to be used for preparing medicines for treating immune diseases such as nephrotic syndrome.

Provided herein are methods for the production of tissue resident memory-like T cells by the combination of hypoxia and TGFβ. Further provided herein are methods of using the tissue resident memory T cells as adoptive cell therapy.

The present disclosure relates to methods of manufacturing Chimeric Antigen Receptor (CAR) T cells. Notably, the manufacturing method omits the CD14+ / CD25+ depletion step. Additionally, by starting with CD62L enrichment of naïve and memory T cells, the resulting CAT T cells show reduced release of proinflammatory cytokines. Furthermore, the transduced cells show improved quiescence after removal of the transactivation agent.

Described herein are methods for reducing tissue resident memory T cells (TRM) in the skin, as well as a method for treating, ameliorating, and / or preventing autoimmune and inflammatory diseases or disorders in the skin. These methods include downregulating the expression of GSPT1 in the tissue resident T cells. Also described are methods for screening therapeutic targets for regulating T cell functions.

Provided herein are compositions comprising a liposome comprising RNA molecules and a cationic lipid, wherein the RNA molecules encode at least one MHC Class II epitope of a mutant Histone 3 (H3) protein comprising a K27M mutation and optionally at least one MHC Class I epitope of the mutant H3 protein. In exemplary embodiments, the RNA molecules comprise a sequence of SEQ ID NO: 12 or 14. Methods of increasing central memory T cells, increasing an immune response, or treating a diffuse midline glioma (DMG), in a subject are provided herein. In exemplary embodiments, the methods comprise administering to the subject the compositions provided herein.

Methods of generating memory T cells in vitro are provided. The methods include culturing a population of T cells with a population of antigen-loaded dendritic cells for at least about 28-48 days in a culture medium and isolating memory T cells (such as CD4+ or CD8+ memory T cells) from the culture. Methods of treating a subject with cancer or infectious disease are also provided. The methods include administering to the subject memory T cells generated by the methods described herein, where the antigen-loaded dendritic cells are loaded with an antigen expressed by the cancer or the infectious agent causing the disease. Also provided are methods of identifying T cell receptors that specifically bind to an antigen recognized by a memory T cell, which include producing a population of memory T cells recognizing an antigen as described herein, and identifying the T cell receptor expressed by the memory T cells.

A method of T-cell expansion which directs differentiation towards central memory T-cells (Tcm). Also provided is a device to promote Tcm directed T-cell differentiation and high yield expansion, which may be employed in the presently disclosed method of T-cell expansion; and a method for screening to identify a process that modulates differentiation of T cells into Central Memory T cells (Tcm) subpopulation ex-vivo.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPαlow macrophages that are useful for treating cancers.

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 present disclosure provides methods for preparing improved populations of cells of the T lineage of, specifically, naive-like T cells that comprise naive T cells (TN), stem-cell like memory T cells (TSCM), and central memory T cells (TCM). The method is based on enrichment for cells expressing a marker of circulating innate lymphoid cell precursor cells. The present disclosure further provides populations of these naive-like T cells, compositions thereof, and uses thereof in treating immune-related disorders.

Disclosed is a method for in vitro expansion of tumor-infiltrating lymphocytes. Developed are a new method for isolating and enriching TIL cells in tumor tissues and an optimized culture method for TIL cells independent of feeder cells. 1010 grade or more of TIL cells having an anti-tumor function can be obtained. By means of cell phenotype analysis, compared with TILs expanded by the traditional two-step method, the cultured TIL cells have a higher proportion of memory T cells and a lower proportion of exhausted T cells and regulatory T cells.

Provided herein are improved methods of treating cancer in humans by activating resident memory T cells in tumors using one or more antigenic peptides.

The present invention relates to compositions and methods for generating a nucleic acid delivery system comprising a nucleic acid sequence encoding a heterologous protein comprising a canine tumor-specific antigen (canine melanoma polyepitope (K9Melapoly)) and an inhibitor of an immuno-inhibitory pathway (HSV-1 gD). Additionally, the current invention includes compositions and methods of treating and / or preventing or immunizing a canine against melanoma, and methods of inducing an effector and memory T cell immune response in a canine administered the nucleic acid delivery system of the invention. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a canine as well as a protein expression system.

The present invention relates to chimeric antigen receptors (CARs) comprising a T cell receptor (TCR) hinge region and a transmembrane domain. The invention also relates to the use of transmembrane domain pairing to enhance the stability and specificity of dual antigen CARs. In addition, the present invention relates to novel CAR constructs comprising a transmembrane domain derived from a cytokine receptor and a signal domain.

The invention belongs to the technical field of biological medicine, and particularly relates to application of vitamin B12 in preparation of an auxiliary therapeutic agent for preventing or treating colorectal cancer precancerous lesions. The invention aims to solve the technical problem of providing a novel prevention and intervention means for colorectal cancer (CAC) caused by the cancerization process of colorectal adenoma and inflammatory atypical hyperplasia. The invention further provides a preparation method of the novel prevention and intervention means for the colorectal cancer caused by the cancerization process of the colorectal adenoma and the inflammatory atypical hyperplasia of the colorectal adenoma and the colorectal cancer caused by the inflammatory atypical hyperplasia of the colorectal adenoma. In a colorectal adenoma canceration process, the level of vitamin B12 in a circulatory system is reduced along with the development of diseases. In inflammatory and hereditary colorectal cancer mouse models, MHC-II signals can be enhanced by supplementing medicine vitamin B12, and CD4 effect memory T cell immunity can be reactivated. The invention provides a new thought for further researching the immune recovery strategy in the colorectal cancer precancerous lesion process and the medical application of the vitamin B12.

The present invention relates to a highly active transposase protein for a transposon system and its uses. By improving the activity of the transposase, genes can be delivered effectively, which can be useful for developing genome-modified cell lines that express various genes. In addition, when T cells are transformed using the highly active transposase of the present invention, cytotoxic T cells (CD8) that have anti-cancer effects can be generated. + The proportion of T cells increases, and T cells persist in the body. CM (Central memory T cell), T SCM Since the proportion of memory-type T cells (stem cell-like memory T cells) increased, it is expected that TCR-T cells and CAR-T cells with good in vivo persistence can be produced using the transposon system of the present invention.

The invention provides a method for detecting cynomolgus monkey activated memory T cells and tissue resident memory T cells through flow cytometry, and belongs to the technical field of biological detection. According to the invention, a stable and reliable flow cytometry detection method is established by optimizing a specific fluorescent antibody combination and a detection process. The method has the direct effects that a plurality of key T cell subgroups including activated memory T cells and tissue resident memory T cells can be clearly identified at one time from peripheral blood and nasal mucosa samples of cynomolgus monkeys, the detection result is accurate, and the repeatability is good. The establishment of the method provides key technical support for comprehensive and deep evaluation of immune response, especially local immune memory of mucous membrane parts in preclinical drug safety and immune efficacy evaluation, and has important application value for research and development of biological medicine products such as vaccines and immunomodulators.