51 results about "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.

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 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 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.

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.

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 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.

The invention relates to the field of immunology, in particular to preparation of a mucous membrane adjuvant for recruiting pre-DC and application of the mucous membrane adjuvant in influenza vaccines. Tridecafluoroheptyl ethylene oxide and mannose are grafted on polyethyleneimine, the polyethyleneimine and structural protein hemagglutinin of influenza viruses are adsorbed to form a nano vaccine MF25PEI / HA, secretion of CCL2 is promoted by activating a TLR4 pathway of nasal cavity cDC, pre-DC is recruited and differentiated into cDC, and the network steady state of the nasal cavity cDC is maintained. HA uptake is increased by targeting cDC, cDC maturation is stimulated, and high-level immune response is induced. After intranasal immunization of MF25PEI / HA, secretion of high-level IgA and IgG is caused, activation of B cells, T cells and Tfh cells is promoted, and differentiation of memory B cells and memory T cells is induced. Effective protection can be provided for the influenza H1N1 virus, and a new thought is provided for research and development of respiratory mucosa vaccines.

The invention belongs to the technical field of biomedicine, and particularly relates to application of CD69 + CXCR6 + gamma delta T cells in preparation of a medicine for preventing and / or treating hepatic fibrosis. It is revealed for the first time that the liver resident memory T cell CD69 + CXCR6 + gamma delta T cell subset can kill the HSCs, secretion of Th1 type cytokines IL-2, IFN-gamma and the like is promoted, fibrosis liver can be precisely targeted according to the natural homing characteristic, the survival time of cells after reinfusion and formation of the memory T cells are prolonged, and by inhibiting activation of the HSCs, the effect of killing the HSCs is achieved. The effect of inducing apoptosis to reverse hepatic fibrosis is achieved, and the technical defect that a traditional CAR-T therapy is insufficient in targeting in solid organ diseases is overcome.

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 biological medicines, and particularly discloses a vaccine adjuvant composition as well as a preparation method and application thereof. The vaccine immune composition provided by the invention comprises GM-CSF and cortex albiziae saponin, and has the following advantages: 1, the vaccine immune composition can significantly improve the specific antibody level and the cytokine secretion efficiency, effectively promote the activation of killer T cells, efficiently induce the response of memory T cells, and construct a stable immune defense basis; 2, the immune level of the organism can be remarkably improved after challenge, the tissue injury risk is reduced by inhibiting replication and colonization of viruses in key target organs, and meanwhile, the body weight of the organism is promoted to be quickly recovered after challenge, so that the physiological homeostasis of the organism is better maintained; thirdly, the method is wide in adaptability and can be compatible with various veterinary vaccines such as foot-and-mouth disease vaccines, porcine reproductive and respiratory syndrome vaccines, pseudorabies vaccines and porcine circovirus type 2 vaccines. The method can be applied to the fields of research, development and preparation of vaccine adjuvants or vaccines and the like.

This invention relates to the field of tumor vaccines, specifically to an anti-tumor vaccine, its preparation method, and its application. The invention prepares an anti-tumor vaccine, BCG-CW@LNT, by mixing cell walls extracted from BCG vaccine as an immune adjuvant with LNT cells obtained from tumor cells through rapid freeze-thaw cycles in liquid nitrogen. This vaccine utilizes these "therapeutic dead cells" to induce a broad antigen response throughout the entire cell, mimicking the natural presentation of antigens in the tumor microenvironment, thereby enhancing anti-cancer immunity. In bladder cancer and lung cancer models, BCG-CW@LNT demonstrated good anti-tumor therapeutic effects. Furthermore, due to the presence of memory T cells, it exhibits a long-term memory effect, providing long-term anti-tumor and preventative effects, effectively preventing tumor recurrence and offering a novel option for tumor treatment.

The invention relates to the technical field of tumor immunotherapy, in particular to an immunotherapy composition for enhancing functions of resident memory T cells of tumor tissues and application of the immunotherapy composition. The immunotherapy composition comprises an FLT3 signal channel activator and IL-10 or a functional variant thereof; the IL-10 or the functional variant of the IL-10 is an Fc-IL-10 fusion protein, and is formed by connecting a human source IL-10 and a human IgG1 Fc segment through a GGGGS connecting peptide; the FLT3 signal channel activator is an FLT3 ligand (FLT3LG) or an overexpression vector comprising an FLT3 extracellular domain, a transmembrane domain and an intracellular kinase domain. By synergistically inhibiting apoptosis, reversing functional depletion and remodeling an immune microenvironment, the solid tumor treatment effect is remarkably improved.