102 results about "Memory T cell" patented technology

Disclosed herein are compositions and methods for modulating T cells. For example, the compositions and methods may be used to increase memory T cells. The compositions and methods may increase the expression or protein level of a transcription factor selected from TGIF2LX, TGIF1, TGIF2, FOS, HNF4A, KLF8, NFKBIZ, CARF, EBF3, HMX3, LHX4, LMX1A, PLAG1, PLAGL1, POU2F3, SOX14, TFAP2D, and WT1, or a combination thereof. The compositions and method may be used in combination with Adoptive T Cell Therapy (ACT) to enhance the ACT.

Disclosed herein are compositions and methods for modulating T cells. For example, the compositions and methods may be used to increase memory T cells. The compositions and methods may increase the expression or protein level of a transcription factor selected from THAP6, DMRT3, MEF2B, PAX2, ATOH7, KLF2, KLF1, TWIST1, NKX6, and FEV, or a combination thereof. The compositions and method may be used in combination with Adoptive T Cell Therapy (ACT) to enhance the ACT.

The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem / progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem / progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of naïve conventional αβ-T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.

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.

The present invention provides a tumor neoantigen vaccine system specifically marking a heterologous protein, and a use thereof. The vaccine system is composed of a heterologous protein mRNA vaccine and a recombinant oncolytic virus; the heterologous protein mRNA vaccine is used to induce an organism to generate heterologous protein-specific memory T cells, and the recombinant oncolytic virus is used to promote a tumor to express microorganism-derived tumor neoantigens. When pre-immunized memory T cells detect these marked specific neoantigens, the tumor expressing the neoantigens is quickly activated and killed, the release of tumor autoantigens is promoted, dendritic cells phagocytize antigens to further initiate an anti-tumor response, and a systemic anti-tumor immune effect is activated by means of antigenic epitope spreading.

A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and / or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

A method to obtain more effective CAR-T cells, which are FOXO1 inhibited. The inhibition of FOXO1 potentiates the ability to induce lysis of a target cell thanks to the increased expression of TNF-α and other inflammatory cytokines, induces spontaneous cell polarization comparable to that obtained by stimulation with chemokines and thus improves the motility of the cells, induces a sharp increase of memory T cells and allows to obtain more efficient CAR-T cells to treat solid tumors than classical CAR-T cells obtained with the known protocol. An 10 ex vivo method to obtain improved CAR-T cells including the steps of (i) cultivate T cells obtained from a subject with a FOXO1 inhibitor during a time of 2 to 10 days; (ii) transducing (or transforming) the T cells into CAR-T cells thanks to a known method.

Disclosed herein are compositions and methods for modulating T cells. For example, the compositions and methods may be used to increase memory T cells. The compositions and method may be used in combination with Adoptive T Cell Therapy (ACT) to enhance the ACT.

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 invention belongs to the field of bioengineering, and particularly relates to an in-vitro culture method of CD8 < + > dry memory T cells, a product and application of the product. The method comprises the following specific steps: (1) coating, stimulating and activating T cells by using an anti-CD3 antibody and RetroNectin; (2) performing resting culture on the activated T cells in a resting culture solution for 0-60 hours; and (3) adding cell factors into the resting culture solution to perform large-scale multiplication culture on the T cells after resting. According to the method, the efficiency of obtaining the CD8 + TSCM cells through in-vitro culture is improved, the culture process is simplified, and the risk of microbial contamination in the culture process and the cost of obtaining the CD8 + TSCM cells are reduced.

To provide compositions for the diagnosis and treatment of immune related diseases and methods of using those compositions.SOLUTION: A method of determining whether a test immune cell is an activated or normal Treg, memory T cell, NK cell, or TFh cell, the method comprising assessing the level of expression of TIGIT in the test immune cell and comparing the level of expression of TIGIT in the test immune cell to the level of expression of TIGIT in a known activated or normal Treg, memory T cell, NK cell, or TFh cell, or comparing the level of expression of TIGIT in the test immune cell to one or more known standard TIGIT expression values.SELECTED DRAWING: None

A method may include, by at least one data processor and based on a set of cytokinetic parameters corresponding to a plurality of T-cell phenotypes and the plurality of T-cell phenotypes, identifying a plurality of T-cell phenotypes in peripheral tissue and lymph node compartments (i.e., T-cell phenotypes, T-cell phenotypes, T-cell phenotypes, T-cell phenotypes, T-cell phenotypes, T-cell phenotypes, and T-cell phenotypes). The distribution of the plurality of T cell phenotypes over time is determined based on a transport rate between the plurality of T cell phenotypes (e.g., a healthy tissue compartment), a blood compartment, a tumor drainage lymph node compartment, and a tumor compartment. The plurality of T cell phenotypes may include stem cell-like memory T cells, central memory T cells, effector memory T cells, effector T cells, and endogenous T cells. Related methods and articles are also disclosed.

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.

Phosphatidylserine (PS)-targeting biomolecules and related methods for impacting the function of memory T cells are provided. In the present methods, PS-binding biomolecules are delivered to peripheral blood mononuclear cells (PBMCs) or whole blood of a subject in the presence of antigens specific to one or more diseases, wherein the PBMCs or whole blood comprise memory T cells that are exhausted or non-responsive to the antigens specific to the one or more diseases. Delivery of the PS-binding biomolecules to the PBMCs or whole blood restores effector function in the antigen non-responsive memory T cells. The administration of PS-binding biomolecules to PBMCs or blood with T cell antigens specific to pathogens can also be used to develop ultrasensitive diagnostics for latent infections or memory T cells response induced by natural infection or vaccination.

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.

The invention discloses a cell engineering method for reversing PD1 signals of T and CAR-T cells by using CD27. Specifically, the invention discloses a fusion protein PD1-CD27 (SEQ ID No. 4) and a nucleic acid molecule (SEQ ID No. 1), and further constructs a modified T cell for different antigens. The modified T cell has small influence on the phenotypes of CD4 and CD8-T cells of a patient, the proportion of memory T cells is increased, and the modified T cell can survive for a long time, specifically recognizes and kills tumor cells expressing tumor-associated antigens (mesothelin, HER2 and the like), has no killing effect on negative cells, and has the effects of resisting a tumor cell microenvironment and resisting T cell depletion. The CD27 is used for reversing an inhibition signal of PD1, and the CD27 has practical significance and potential clinical application value for overcoming a tumor microenvironment, playing a cytotoxic role in the microenvironment and prolonging the survival time of CAR-T.

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

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.

The invention relates to application of a dry memory T cell in preparation of a medicine for treating colorectal cancer pulmonary metastasis, and belongs to the technical field of biological medicine. The invention firstly proves that the capability of differentiating the Tscm cells into effector killer T cells can be effectively improved by knocking out the Erbin genes in the Tscm cells in a mouse body, lung metastasis of colorectal cancer is inhibited, and the treatment effect of CAR-T cells can be enhanced by the Tscm cells with the Erbin genes knocked out. In addition, xanthine is detected for many times in a mouse colorectal cancer lung metastasis focus after the Erbin gene in the Tscm cell is knocked out, hypoxanthine can promote generation of more Tscm cells in the tumor metastasis focus, and the Tscm cells are differentiated to generate killer T cells, so that colorectal cancer lung metastasis is inhibited. The metabolic pathway of hypoxanthine is further studied, it is found that allopurinol can inhibit conversion of hypoxanthine into xanthine and uric acid, and it is found that allopurinol can also inhibit colorectal cancer lung metastasis by injecting allopurinol into a colorectal cancer lung metastasis mouse model.

The invention discloses a dry memory T cell in-vitro induction and amplification method based on metal ion regulation and application thereof. According to the method, Mn < 2 + > is added in the cell culture process to effectively induce the T cells to differentiate to the dry memory phenotype, so that the production cost of the dry memory T cells is greatly reduced while the use of other cell factors and chemical inducers is reduced. The dry memory T cell obtained by adopting the method has good multiplication capacity and functional activity, is suitable for clinical treatment, and particularly shows a wide application prospect in anti-tumor immunotherapy.

Provided herein are vaccine compositions comprising recombinant protein antigens derived from computationally optimized broad reactive influenza antigen (COBRA) proteins and immunomodulators and methods of using the same. In some embodiments, the vaccine composition comprises one or more COBRA proteins, and the immunomodulator is a cationic lipid. The cationic lipid is prepared from R-DOTAP (4, 4 ', 4' '- Methods of use of the vaccine composition include a method of inducing a humoral immune response against influenza virus in a subject, a method of inducing multifunctional CD8 + and CD4 + effector T cells against influenza virus, a method of inducing memory T cells against influenza virus, and a method of inducing multi-functional CD8 + and CD4 + effector T cells against influenza virus. Methods of enhancing immunity against influenza viruses and methods of inducing a balanced Th1 / Th2 immune response against influenza viruses.

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.

Pre-existing alloreactive memory T cells are a major barrier to the induction of allograft tolerance in organ transplant recipients. The use of Eomesodermin (Eomes) expression in memory T cells to determine the risk of allograft rejection in a subject is described. Also described is the use of Eomes expression in memory T cells of transplant recipients to modify immunosuppressive therapy.

The present invention relates to a new and specific T-cell therapy strategy based on the use of memory stem T-cells (Tscm), in particular highly functional memory stem T-cells (Tscm) negatively selected on the basis of inhibitory receptor expression. This new cellular immunotherapy may be applied to PML patients but also to other infections or cancers for which the specific memory T cell responses are functionally impaired.