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

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 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.

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.

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 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.

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.

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.

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 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.

The invention belongs to the technical field of new application of medicines, and particularly relates to application of itraconazole in preparation of a product for amplifying an induced T cell into a central memory T cell in vitro. It is found through experiments that itraconazole is additionally added into a CAR-T cell culture medium, CAR-T cells can be rapidly induced, differentiated and amplified into central memory CAR-T cells in vitro, and the proportion of the central memory CAR-T cells in the CAR-T cells is obviously increased. Itraconazole is a clinical medicine, pharmacokinetic and toxicological studies are clear, the safety is high, good technical support is provided for tumor cell treatment, and the itraconazole has important significance.

The invention belongs to the field of immunology, and particularly relates to a method for constructing an animal model and application thereof. The method comprises the following steps: firstly, providing a method for constructing a mouse model, namely constructing four transgenic mice by using artificial chromosomes, two different DNA recombinase and three different reporter genes, and mating to obtain the transgenic mice carrying the three different reporter genes at the same time, the mouse can be used for tracking Th1 cell differentiation and central memory T cell development in an animal body. The invention also provides a method for evaluating the immune efficacy of the vaccine, which comprises the following steps: immunizing a mouse according to an immune procedure and a dose capable of causing immune response, extracting lymphocytes of the mouse, performing flow cytometry staining, and observing a result. Through a constructed mouse model, it is found that differentiated Th1 type effector cells capable of stably expressing T-bet can be developed into CCR7 + CD4 + TCM cells, and analysis of functions and development differentiation of the cells can provide a new thought for development of cellular immune vaccines with higher effector functions and long protection periods.

Provided is a cell scaffold material that can bring about good maintenance of memory T cells and good T cell proliferation.　A cell scaffold material according to the present invention is used for culturing a cell population containing T cells and contains a peptide-containing resin (A) having a synthetic resin part and a peptide part. The peptide part has a first peptide part and a second peptide part. The first peptide part and the second peptide part have different amino acid sequences. The first peptide part can bind to a first integrin, and the second peptide part can bind to a second integrin. The dispersive component γd of the surface free energy of the cell scaffold material is at least 24.5 mJ / m2 and not more than 45.0 mJ / m2, and the dipole component γp of the surface free energy of the cell scaffold material is at least 1.0 mJ / m2 and not more than 20.0 mJ / m2.

The application provides an LNP-mRNA and connector macrophage for connecting T cells, macrophages and tumor cells and application thereof, and relates to the technical field of biotechnology.The mRNA of the chimeric antigen receptor of the application for targeting tumor cells, the mRNA of CD80 and the mRNA of the anti-CD3 single-chain antibody are wrapped by the lipid nanoparticles, three kinds of mRNA can be simultaneously delivered and are taken by macrophages and tumor cells, the engineered macrophages with the connector effect are formed, and then the macrophages, T cells and tumor cells are combined together and the T cells are activated.The macrophages and the activated T cells can synergistically play the tumor killing effect, meanwhile, the macrophages can also promote the formation of memory T cells, and realize long-term tumor monitoring and inhibition effect.Different from the existing connector, the existing connector is in the form of antibody, and the application is in vivo edited macrophages.

The application belongs to the technical field of new use of medicines, and particularly relates to application of itraconazole in preparation of a product for inducing T cells to be central memory T cells in vitro. It is found through experiments that, by additionally adding itraconazole in a CAR-T cell culture medium, CAR-T cells can be rapidly induced and differentiated to be central memory CAR-T cells in vitro, and the proportion of the central memory CAR-T cells in the CAR-T cells is obviously increased. Itraconazole is a clinical drug, and pharmacokinetics and toxicology research is clear, and the safety is high. The application provides good technical support for tumor cell treatment, and has important significance.

Compositions comprising memory T cell Targeting Constructs comprising an anti-T cell antibody or antigen-binding portion thereof linked to a near-infrared photoactivated cytotoxin, e.g., a photoactive adduct of an infrared dye, and methods of use thereof for reducing numbers of pathogenic T cells selectively in peripheral tissues e.g., for treating inflammatory and autoimmune diseases.

The invention discloses an AC (at) Mg / Ce-UiO nano particle, a preparation method thereof and application of the nano particle in medicines for treating inflammatory dermatosis, and belongs to the technical field of biological medicines. Adenylate cyclase (AC) is encapsulated in situ in an Mg / Ce-UiO metal organic framework designed by defect engineering, and a unique structure brings dual treatment strategies: the encapsulated AC catalyzes pro-inflammatory ATP to be converted into anti-inflammatory cAMP to restore balance; defective Mg / Ce-UiO simulates SOD (superoxide dismutase) and CAT (catalase) to remove excessive ROS. The nanoparticles can down-regulate the expression of various inflammatory factors and pruritus mediators, inhibit the excessive proliferation of keratinocytes and reduce the infiltration of immune memory T cells. Therefore, the effects of treating inflammatory skin disease skin lesion, remarkably relieving itching and preventing relapse are achieved. The preparation method is simple and easy for large-scale production. The invention introduces a reform mode to the treatment of inflammatory dermatosis, provides a curative strategy, establishes a multifunctional treatment framework, and is expected to be suitable for more extensive inflammation and autoimmune diseases.

Small peptides, and a use thereof in the preparation of a medicament for treating cancer. Provided are a group of DSP small peptides, as well as full-length and truncated DDR1 proteins, all of which have the same active structure. Using in vivo tumor experiments, it is demonstrated that this group of DSP small peptides or truncated proteins can increase stem-like CD8+ memory T cells in bone marrow, and enhance the cytotoxic activity of CD8+ effector T cells, ultimately inhibiting the metastasis of lung cancer cells to brain tissue. In vitro, it is demonstrated that they have cytotoxic effects on tumor cells of eight types, including lung cancer, breast cancer, colorectal cancer, melanoma, prostate cancer, liver cancer, pancreatic cancer and bladder cancer.

Aspects of the disclosure include modified T cells that are MED12K0 and mbIL-12+, and preferably naive-like stem cell memory T cells that are CCR7+, CD62L+, CD45RA+, enriched populations of said cells, and methods of making and using same, including to extend the persistence and / or longevity of the modified immune cells in vivo.

The application provides application of a substance for detecting lymphocyte subpopulation ratio in preparation of a Graves' disease diagnosis or auxiliary diagnosis reagent or kit, and belongs to the technical field of disease diagnosis reagent preparation. Research finds that, compared with a healthy sample, the proportion of B cells in a lymphocyte subpopulation of a sample to be detected is significantly increased, the proportion of NK cells is significantly reduced, the proportion of activated T cells is significantly reduced, the proportion of memory T cells is significantly reduced, the proportion of CD4+ memory T cells is significantly reduced, the proportion of Th1 cells is significantly reduced, and the proportion of Tc1 cells is significantly reduced, so that the sample to be detected is a GD patient, and the application has high sensitivity and strong specificity in diagnosis or auxiliary diagnosis of Graves' disease by using the substance for detecting lymphocyte subpopulation ratio.

The present invention provides a non-invasive ex vivo method for diagnosis, prognosis or monitoring of Parkinson's disease (PD) in a subject comprising determining the ratio of CD8 terminally differentiated effector T cells (CD8 TEMRA) to CD8 central memory T cells (CD8 TCM) in a biological sample from the subject, as well as a computer program product for implementing the method. Also provided herein are kits (particularly kits for diagnosis, prognosis or monitoring of PD) and uses thereof, the kits comprising: (a) means specifically suitable for determining the ratio of CD8 TEMRA to CD8 TCM; and (b) optionally a reference of said ratio or means for establishing said reference wherein said reference represents a known diagnosis or prognosis of PD wherein (a) and optionally (b) are the only biological agents present in said kit.

The application discloses a culture medium for CAR-T cell culture and application thereof, and relates to the fields of immunology, molecular biology and cell engineering. The culture medium comprises a basic culture medium and dihydroeugenol. It is found in research that by adding dihydroeugenol in the culture medium, the proportion of central memory T cells of CAR-T cells can be effectively improved, and the expression levels of PD1 and LAG3 can be reduced. In addition, dihydroeugenol can also promote the secretion of IL2, TNF and INFgamma, and enhance the killing function of CAR-T cells. Experiments show that the ability of D-CAR-T to secrete IL2, TNF and INFgamma is significantly higher than that of ordinary CAR-T, and D-CAR-T also has a higher T CM cell proportion and a lower exhaustion level after performing the killing function.