42 results about "Helper t-cells" patented technology

The invention discloses a preparation method and application of porcine pseudorabies virus multi-epitope polypeptide, and belongs to the technical field of veterinary biological products. The multi-epitope polypeptide comprises a cytotoxic T cell epitope, a helper T cell epitope and a linear B cell epitope; the cell epitopes are screened from key immunogenic proteins of the pseudorabies virus by using an immunoinformatics method. The porcine pseudorabies virus multi-epitope polypeptide designed by the invention is high in safety, has better antigenicity and physicochemical properties, can be efficiently expressed, and can be recognized by a pseudorabies virus specific antibody. By applying the porcine pseudorabies virus multi-epitope polypeptide, high-level specific antibodies and cellular immune response can be continuously induced to generate, strong protective efficacy is generated, and mice can be protected from death when infected with a lethal dose of porcine pseudorabies virus. Therefore, the multi-epitope polypeptide disclosed by the invention can be used as an alternative antigen of a porcine pseudorabies virus vaccine, the use of active virus is avoided, and a tool is provided for eradication of porcine pseudorabies virus.

An object is to provide a Th1-increasing agent that can reduce constraints on storage conditions and feeding form and sufficiently increase Th1 at lower doses. A Th1-increasing agent containing a cellulose derivative as an active ingredient, the cellulose derivative having a degree of butyryl substitution of 0.3 or greater and 2.6 or less, and a total degree of substitution of 0.5 or greater and 2.8 or less.

The present application provides a CD4 helper T cell epitope fusion peptide, its encoding nucleic acid and an immune composition comprising the same. The epitope fusion peptide comprises a cytomegalovirus epitope. The epitope fusion peptide provided by the present application can greatly improve the cellular immune response level of the target immunogen, especially a weak immunogen, and is an effective means to overcome the immune system's immune tolerance to antigens, especially tumor antigens or infection-related antigens, and is suitable for efficiently enhancing the efficacy of vaccines.

The invention relates to the technical field of biology, in particular to a human CD4 and TGF-beta1 / 2 / 3 combined bispecific antibody which at least comprises a first protein functional area, and the first protein functional area comprises a first antigen binding site targeting CD4; and the second protein functional region comprises a second antigen binding site targeting TGF (Transforming Growth Factor)-beta 1 / 2 / 3. The bispecific antibody disclosed by the invention can be well and specifically combined with CD4 and specifically combined to helper T cells; meanwhile, the bispecific antibody can be combined with TGF beta 1, so that Th1 cell mediated cellular immunity is activated, TGF beta 2 and TGF beta 3 are neutralized, and the bispecific antibody has the effect of preparing the medicine for preventing and treating bacterial infectious diseases.

The present invention relates to a separated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen binding domain, and the extracellular antigen binding domain comprises an antibody or antibody fragment that binds to a human CXC chemokine receptor type 5 (CXCR5) protein. The present invention further relates to nucleic acid molecules encoding the CAR of the present invention, genetically modified immune cells expressing the CAR of the present invention, preferably T cells, and the use of the cells in the treatment of medical conditions related to the presence of pathogenic cells expressing CXCR5, wherein the pathogenic cells expressing CXCR5 are preferably pathogenic mature B cells and / or memory B cells and / or pathogenic T cells and / or follicular helper T cells, particularly mature B cell non-Hodgkin lymphoma (B-NHL), T cell non-Hodgkin lymphoma, or autoantibody-dependent autoimmune diseases, preferably selected from systemic lupus erythematosus (SLE) or rheumatoid arthritis.

The present invention relates to the field of adoptive immune cell therapy, e.g., adoptive T cell therapy. It provides immune cells, such as be gamma delta T cells, CD4 helper T cells, mucosa-associated invariant cells, innate lymphoid cells, NK cells, macrophages or other types of immune cells or a combination thereof, engineered to express a CD8 co-receptor, and it provides an advantageous configuration of a nucleic acid encoding a CD8 alpha beta co-receptor, wherein the nucleic acid comprises a construct capable of mediating expression of the CD8 alpha and CD8 beta chain under the control of one promotor from a polycistronic mRNA. This improves adoptive immune cell therapy, e.g., it may improve function and persistence of engineered immune cells. The nucleic acid can optionally further encode TCR alpha and beta chain constructs. It can also encode a chimeric antigen receptor. The immune cells may express an alpha beta TCR construct as well as a suitable co-receptor, in particular, an MHC I-restricted alpha beta TCR construct as well as a CD8 co-receptor. Pharmaceutical compositions comprising said cells or nucleic acids are also provided. These are useful for treatment of cancer or infectious diseases.

The invention belongs to the technical field of genetic engineering, and particularly relates to a bovine group A rotavirus multi-epitope fusion protein and application thereof. The invention provides a bovine group A rotavirus multi-epitope peptide based on a ferritin nano-carrier, a fusion protein and application of the bovine group A rotavirus multi-epitope peptide and the fusion protein. The multi-epitope peptide disclosed by the invention is a multi-epitope fusion antigen which is formed by splicing cytotoxic T lymphocyte epitopes, helper T cell epitopes and B cell epitopes with high conservative property and strong immunogenicity and is formed by screening and obtaining the cytotoxic T lymphocyte epitopes, helper T cell epitopes and B cell epitopes with high conservative property and strong immunogenicity on the basis of VP4 and VP7 protein sequences of bovine group A rotaviruses by utilizing an immunoinformatics technology. Immunological evaluation shows that the monoclonal antibody has good antigen specificity and neutralizing activity. Animal experiment results show that the epitope peptide and the fusion protein can induce an organism to generate high-level neutralizing antibodies aiming at BRVA G6, G8, G10 and other multi-genotype strains, and the broad spectrum and durability of immune protection are remarkably improved.

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 belongs to the technical field of biological medicines, discloses application of trifluoromethyl tubercle bacillus in preparation of antitumor drugs, and finds that trifluoromethyl tubercle bacillus can significantly inhibit proliferation of liver cancer cells, inhibit tumor volume and prolong survival time of tumor-bearing mice and has a significant antitumor effect. The invention also discovers that the trifluoromethyl tubercle bacillus enhances the anti-tumor immune response by promoting the infiltration of follicular helper T cells in the liver cancer part. According to the invention, the new application of the trifluoromethyl tubercle bacillus is found, the application range of the trifluoromethyl tubercle bacillus is expanded, and a new choice is provided for clinical treatment of liver cancer.

Disclosed are a multivalent Streptococcus pneumoniae capsular polysaccharide-protein conjugate composition and a preparation method therefor. The Streptococcus pneumoniae serotype is selected from 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F. The composition can effectively stimulate the production of helper T cells in the body, promote the activation of B cells, and result in immune memory, so as to enable the antibody class to switch from IgM to IgG and enhance immunogenicity, thereby enabling the infants under 2 years of age to produce effective immune responses against corresponding diseases.

An antigen-loaded nanogel is formed by loading or encapsulating one or more long peptide antigens or one or more protein antigens in a hydrophobized polysaccharide. The long peptide antigen(s) or protein antigen(s) contains (or each contain) one or more CD8+ cytotoxic T cell recognition epitopes and / or one or more CD4+ helper T cell recognition epitopes, which is / are derived from the antigen. The antigen-loaded nanogel is administered at least one day prior to administration of antigen-specific T cells to improve the efficacy of a T cell infusion therapy against an immune checkpoint inhibitor-resistant tumor. The hydrophobized polysaccharide may be pullulan having cholesteryl groups bound thereto. An immune-enhancing agent also may be administered in or with the antigen-loaded nanogel.

The application discloses a use of ursolic acid as a SARS-CoV-2 subunit vaccine adjuvant, aims to solve the technical problems of relatively weak immunogenicity of existing subunit vaccines, possible local or systemic adverse reactions of some adjuvants and unclear action mechanism, and provides a new medical use of ursolic acid. The ursolic acid can effectively improve the antigen-specific antibody level of the subunit vaccine immunized mice, promote the formation of germinal centers and enhance follicular helper T cell response. The action mechanism is that after the ursolic acid is combined with PTPRF, the stability of the PTPRF is affected and the degradation of the PTPRF is promoted, thereby enhancing the downstream STAT3 phosphorylation, promoting the expression of antigen presentation related genes and improving the antigen presentation ability of the dendritic cells, and finally enhancing the antibody response of the body. The application provides a new subunit vaccine adjuvant candidate molecule for preventing severe SARS-CoV-2 related infections in clinic, and provides a new molecular target and mechanism basis for the development of subunit vaccine adjuvants.

The present disclosure provides a prophylactic or therapeutic agent for a benign tumor. Provided is a prophylactic or therapeutic agent for a benign tumor, which comprises a WT1 peptide, an analog thereof, or a nucleic acid molecule encoding the same. In a specific embodiment, the present disclosure provides a prophylactic or therapeutic agent for a benign tumor, which comprises a WT1 peptide, an analog thereof, or a nucleic acid molecule encoding the same. In a preferred embodiment, the prophylactic or therapeutic agent for a benign tumor (e.g., familial adenomatous polyposis) according to the present disclosure comprises a killer-type and / or helper-type WT1 peptide. In a further preferred embodiment, the aforementioned WT1 peptide is a WT1 126 killer peptide and / or WT1 35 helper peptide. In another aspect, provided are WT1 peptide-specific CTLs, a method for inducing WT1-specific helper T cells, and a method for inducing dendritic cells presenting a WT1 peptide.

The invention relates to the field of biological hospitals, and discloses a tumor follicular helper T cell strain for vascular immune mother cell T cell lymphoma as well as a construction method and application of the tumor follicular helper T cell strain. The invention discloses an AITL tumor TFH cell strain, the name of which is human tumor follicular helper T cell AITL-CH1. The strain is preserved in CCTCC; the preservation date is 2025 to 08 to 12; the preservation number is CCTCC (China Center For Type Culture Collection) NO: C2025233 The construction method comprises the steps of isolated culture of primary cells, in-vitro induction culture of TFH cells and isolated passage. The tumor TFH cell strain of the AITL patient is successfully established, the cell strain has stable TFH characteristic phenotype and good multiplication capacity, the limitation of short in-vitro culture period of primary cells is effectively overcome, and a foundation is laid for in-depth study on AITL epigenetic modification and molecular pathogenic mechanism. A reliable and stable cell model is provided for clinical immunotherapy and targeted drug research and development.

The invention relates to the technical field of microorganisms, in particular to lactobacillus kefir and application thereof in the aspect of regulating animal immune functions. The invention provides Kefir lactobacillus brachyphyllum Fanghua, and the preservation number of the Kefir lactobacillus brachyphyllum Fanghua is CGMCC (China General Microbiological Culture Collection Center) NO.27733 Research finds that compared with an immunosuppression model mouse constructed by using hydrocortisone, the weight of immune organs thymus and spleen can be increased, the number of peripheral blood leucocytes can be increased, and immune cell composition and expression of inflammation-related genes can be changed when the mouse is fed with the Lactobacillus kefir Fanghua. Besides, after the excrement of the aged mice fed with the lactobacillus kefir Fanghua is transplanted to the sterile mice, compared with excrement only transplanted to the aged mice, the content of dendritic cells in the spleen of the receptor mice can be reduced, differentiation of helper T cells can be inhibited, expression of inflammation-related genes can be remarkably reduced, and the inflammation-related effects can be improved. Further, the immune inflammatory response of the receptor mouse is regulated.

The present invention belongs to the field of biotechnology, and in particular to a method for constructing a mouse model that can induce helper T cell 17 elimination and verification of its elimination effect. The method utilizes the characteristic that Rorc molecules are key molecules that promote the normal differentiation of Th17 cells, and by inserting diphtheria toxin receptor and red fluorescent protein tdTomato into the Rorc molecule gene expression frame, a Rorc‑T2A‑tdTomato‑P2A‑DTR (abbreviation: Rorc‑DTR) gene-modified mouse model is constructed, which can realize the expression of red fluorescent protein and diphtheria toxin receptor driven by endogenous Rorc gene in mice. Using this model, the inventor can trace mouse Th17 cells by tdTomato fluorescent labeling, and Th17 cells can be killed by giving mouse diphtheria toxin at a specific time point or time period, causing Th17 cell defects, and the role of Th17 cells in specific physiological and pathological processes is studied.

The present invention relates to the field of adoptive immune cell therapy, eg., adoptive T cell therapy. It provides immune cells, such as gamma delta T cells, CD4 helper T cells, mucosa-associated invariant cells, innate lymphoid cells, NK cells, macrophages or other types of immune cells or a combination thereof, engineered to express a CD8 co-receptor, and it provides an advantageous shuffled configuration of a nucleic acid encoding a CD8 alpha beta co-receptor and alpha beta TCR construct, wherein the nucleic acid comprises a construct capable of mediating expres- sion of the CD8 alpha and CD8 beta chain as well as TCR alpha and TCR beta chain constructs under the control of one promotor. This improves adoptive immune cell therapy, e.g., it may improve function and persistence of engineered immune cells. The immune cells may express an MHC I-restricted alpha beta TCR construct as well as a CD8 co-receptor. Pharmaceutical compositions comprising said cells or nucleic acids are also provided. These are useful for treatment of cancer or infectious diseases.

The invention relates to a method for evaluating the immune state of obese people and a kit thereof, relates to the technical field of medical data mining, and comprises an index combination for evaluating the immune state of the obese people. The index combination comprises the following indexes: hematocrit (HCT), hemoglobin content (HGB), low membrane potential percentage (Ts.MMPlow%) of killer T cells, percentage (T4Tcm%) of central memory assistant T cells, low membrane potential percentage (T8Tn.MMPlow%) of pure killer T cell mitochondria, percentage (NKT.NKG2D +%) of NKT cell expression NKG2D and mitochondrial mass (T8Tcm. MM) of central memory killer T cell mitochondria. The index combination obtained through screening has high biological interpretation and clinical correlation, and the immune state of obese people can be effectively evaluated.

The invention discloses a method for preparing O-type foot-and-mouth disease virus multi-epitope virus-like particles through escherichia coli as well as a product and application thereof. The method comprises the following steps: inserting nucleic acid for coding O-type foot-and-mouth disease virus multi-epitope virus-like particles into a prokaryotic expression vector, then converting the prokaryotic expression vector into escherichia coli competent, and carrying out protein expression and purification, wherein the sequence of the nucleic acid for coding the O-type foot and mouth disease virus multi-epitope virus-like particle is as shown in SEQ ID NO. 5. The O-type foot and mouth disease virus multi-epitope VLP antigen is designed by taking HBc protein as a skeleton and all topological representative strain antigen epitopes of O-type foot and mouth disease virus separated in China as elements and introducing T cell epitopes, the antigen spectrum is wider, auxiliary T cell epitopes are introduced, rapid immune response can be excited in an early stage, and the recombinant antigen is soluble in expression, so that the recombinant antigen can be used for preparing the O-type foot and mouth disease virus multi-epitope VLP antigen for the O-type foot and mouth disease virus. And only the soluble antigen needs to be purified, so that the purification step is simplified, the antigen loss is reduced, and industrial production can be realized.

The present disclosure provides a composition for preventing or treating a benign tumor. Provided is a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a specific embodiment, the present disclosure provides a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a preferred embodiment, the composition for preventing or treating a benign tumor (e.g. familial adenomatous polyposis) according to the present disclosure comprises a killer type WT1 peptide and / or a helper type WT1 peptide. In a further preferred embodiment, the WT1 peptide is WT1126 killer peptide and / or WT135 helper peptide. In another aspect, provided are a method of inducing WT1 peptide-specific CTLs, a method of inducing WT1-specific helper T cells, and a method of inducing dendritic cells presenting a WT1 peptide.

The invention discloses application of valeriana jatamansi jones. The valeriana jatamansi jones are derived from dry roots and rhizomes of valeriana jatamansi jones, and the valeriana jatamansi jones can regulate cell balance of CD4 < + > helper T cells in a human immune system so as to relieve colon tissue pathological damage and mucoprotein secretion abnormality. The traditional Chinese medicine composition can protect the colon tissue pathological injury and mucous membrane layer of the UC mouse, repair the colon pathological injury, regulate and control the balance of intestinal immune cells, and is high in safety coefficient.

The present application relates to cancer immunotherapy, for example, T cell stimulation mediated anti-tumor therapy. Accordingly, disclosed herein are methods of inducing or enhancing an adaptive immune response to a cancer in a subject and methods of treating a cancer in a subject. In some embodiments, the methods hyperactivate dendritic cells (DCs) that induce Type I helper T cell (TH1) and cytotoxic T lymphocyte (CTL) responses in the absence of TH2 immunity.

The purpose of the present application is to provide a composition for inducing follicular helper T cells that are reactive to SARS-CoV-2. The present invention provides a partial peptide of a spike protein of SARS-CoV-2 having a total length of 15 amino acids or less, (1) FKIYSKHTPIN (SEQ ID NO: 1), (2) FQFCNDPFLGVYYHK (SEQ ID NO: 2), (3) KRFDNPVLPFN (SEQ ID NO: 3), (4) LLQYGSF CTQL (SEQ ID NO: 4), (5) PPAYTNSFTRGVYYYP (SEQ ID NO: 5), (6) CSNLLLQYGSF CTQL (SEQ ID NO: 6), (7) SKRSFIELLFNKVT (SEQ ID NO: 8), (9) TNGTKRFDNPVLPFN (SEQ ID NO: 9), (10) NQFNSAIGKIQ (SEQ ID NO: 10), and (11)

The application discloses application of an agonist of ICOSL in preparation of a vaccine, and finds that under follicular helper T cell (T FH ) deficiency conditions, ICOS protein acts as an agonist of ICOSL protein, a nanoparticle vaccine coupled with the agonist of ICOSL can activate ICOSL molecules, directly acts on ICOSL to promote B cell proliferation and expression of anti-apoptosis related genes, can efficiently promote antibody response and differentiation and proliferation of antibody secreting cells; a vaccine coupled with ICOS protein is prepared, targets ICOSL signaling pathways through the coupled ICOS protein molecules, and shows stronger protection effect in anti-coronavirus and HIV vaccines, and especially has better immune effect on immunodeficient / deficient people.

Use of an exosome derived from decidual natural killer (dNK) cells or a dNK cell subset in the preparation of a drug and an auxiliary therapeutic agent for infertility-related diseases is provided. Experiments have confirmed that the exosome treats the endometrial growth disorder-related diseases by promoting increase of endometrial thickness, increasing endometrial cell viability, reducing endometrial cell damage, promoting VEGF expression, and maintaining stemness and stimulating proliferation of endometrial stromal cells, such that a conception rate for endometrial injury model mice increases from 20% to 50%-70%; and the exosome treats the maternal-fetal immune tolerance disorder-related diseases by exerting immune tolerance, reducing a spontaneous abortion rate, and increasing a helper T cell level. In addition, the exosome effectively increases the development rate of eggs fertilized in vivo or in vitro in a multiplying way, and improves an implantation rate and a birth rate for in vitro fertilization and embryo transfer.

The present application belongs to the technical field of genetic engineering, and particularly relates to a bovine rotavirus group A multi-epitope fusion protein and application thereof. The present application provides a bovine rotavirus group A multi-epitope peptide, fusion protein based on ferritin nanocarriers and application thereof. The multi-epitope peptide is based on bovine rotavirus group A VP4 and VP7 protein sequences, and highly conserved and strong immunogenicity cytotoxic T lymphocyte epitopes, helper T cell epitopes and B cell epitopes are screened by using immunoinformatics technology, and are spliced to form a multi-epitope fusion antigen with good conformational stability. Immunological evaluation shows that the multi-epitope fusion antigen has good antigen specificity and neutralizing activity. Animal experiment results show that the epitope peptide and fusion protein can induce the body to produce high-level neutralizing antibodies against multiple genotypes of BRVA G6, G8 and G10, and significantly improve the broad spectrum and durability of immunoprotection.

The present application provides a method, composition, kit and use for detecting interleukin 2 positive type 1 helper T cells (IL-2 + Th1 cells) and / or CD4 + CD25 hi CD127 low regulatory T cells (CD4 + Treg cells). The proportion of IL-2 + Th1 cells is increased and the proportion of CD4 + Treg cells is decreased, which has potential value for independently diagnosing early optic nerve compressive lesions, and the diagnostic efficiency of combined detection of the two kinds of cells is much higher than single detection.

The invention belongs to the field of immunology, and particularly relates to a method for regulating directional differentiation of helper T cell 17 (Th17) and application of the method. The method for regulating and controlling the directional differentiation of the Th17 cells into the Th1 cells is provided firstly, specifically, the activity of a nucleolus composite pore associated protein 4 gene is inactivated or reduced, so that the directional differentiation of the Th17 cells into the Th1 cells is influenced. The invention also provides a pharmaceutical composition, which is a protein and / or a compound and / or RNA for inhibiting the gene function of the gene for directionally differentiating the helper T cell 17 into the Th1 cell. According to the application, the differentiation trend of Th17 to Th1 cells is regulated and controlled on the translation level by knocking out the Noc4L gene by utilizing the regulation and control function of the nucleolus composite pore associated protein 4 in the Th17 cells. The application can provide a new way and means for developing novel nucleic acid drugs to treat autoimmune diseases caused by inflammatory cytokines.

The invention relates to the technical field of biology, in particular to a CD4 / TGF-beta1 binding bispecific antibody which at least comprises a first protein functional area and a second protein functional area, the first protein functional area comprises a first antigen binding site targeting CD4, the first antigen binding site can bind to the 77th site, the 79th site, the 96th site, the 121st-124th site of polypeptide shown as SEQ ID NO: 19, and the second antigen binding site can bind to the 124th-124th site of polypeptide shown as SEQ ID NO: 19. The 127th to 134 amino acids and the 163rd amino acids; and the second protein functional region comprises a second antigen binding site targeting TGF beta 1. The bispecific antibody disclosed by the invention can be well and specifically combined with CD4 and specifically combined to helper T cells; meanwhile, the bispecific antibody can be combined with the TGF beta 1 and is not combined with the TGF beta 2 and the TGF beta 3, so that cardiotoxicity caused by the TGF beta 2 and the TGF beta 3 is avoided. The invention has the effect of preparing medicines for preventing and treating fatty liver.