139 results about "Immunologic Tolerance" patented technology

The invention relates to fusion protein used to prevent and cure I type and II type diabetes and its preparation method and application. It supplies the fusion protein which is formed by glucagon analogy peptide GLP-1, GLP-1 mutant and IgG-Fc, its analogy factor lizard salivary gland polypeptide extendin-4 and IgG-Fc, and the application of the above fusion protein and its DNA used in diabetes prevention and therapy. The fusion protein can increase not only GLP-1 effect, but also the affinity and immunological tolerance of ligand, which is excreted with the form of homogeneity dimmer to improve polypeptide drug effect, overcomes the defect of the GLP-1 for short half-life, and simplifies purification process.

Several embodiments of the present disclosure relate to glycotargeting therapeutics that are useful in the treatment of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent. In several embodiments, the compositions are configured to target the liver and deliver antigens to which tolerance is desired. Methods and uses of the compositions for induction of immune tolerance are also disclosed herein.

The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

Liver-directed gene transfer can induce immunological tolerance to a polypeptide associated with the expression of a therapeutic nucleic acid. Hepatic expression of a transgene induces tolerance to the expression product of the transgene, or to post-translational product related to transgene expression, thereby ameliorating or eliminating the immune responses associated with gene therapy and protein replacement, respectively, independent of the genetic background of the subject.

The invention provides a transfer factor solution for livestock and poultry. Frozen pig spleens are washed clean by use of distilled water, cut into small pieces, added with distilled water free from heat source, subjected to cell disruption by use of a tissue bruiser and prepared into homogenate; the homogenate passes through a high-pressure homogenizer under the pressure of 60 kPa and then is added with a flocculating agent for flocculation; the flocculated homogenate is centrifuged at a centrifugation ambient temperature of 4 DEG C and at a speed of 7,000 r/min; precipitate is removed; supernatant is left on standby; the supernatant is filtered by use of a microporous filtering membrane 0.45 mu m in pore diameter, and then is ultrafiltered by use of a ultrafiltration membrane 5,000 Dalton in molecular weight cutoff so as to obtain a stock solution; after viruses are removed, nicotinamide is added as a stabilizer; the stock solution is subjected to aseptic filtration by use of the microporous filtering membrane; and the obtained product is added with glycerol as a heat-resisting protective agent and then is directly and separately packed. The transfer factor solution can be applied to livestock and poultry. The preparation method is characterized by directly using the pig spleen to extract the transfer factor solution so as to save manpower and materials and improve extraction efficiency. The preparation method combines a heat-resisting protection technique with transfer factors, thereby realizing the normal-temperature preservation of the transfer factors. The transfer factor solution can improve the disease-resisting capability of organisms, relieve immunologic suppression and immunologic tolerance, can play a role in emergency adjuvant treatment, and makes up for immunization blank after vaccination before antibody production.

Novel [1,2,4]triazolo[1,5-a]pyrimidine derivative of the general formula (1): (1) its prodrug or a pharmaceutically acceptable salt thereof, which exhibits an antigen presentation inhibiting activity and is useful as a preventive and/or therapeutic agent for immunological rejection and/or graft versus host reaction in organ/bone marrow transplant, autoimmune disease, allergic disease and/or inflammatory disease and also useful as an anticancer drug or as an immunological tolerance inducer for transplanted organ/transplanted bone marrow.

The invention discloses a cell membrane nano-vesicle wrapping an immunosuppressant and overexpressing PD-L1 and a preparation method and application thereof. The cell membrane nano-vesicle is composedof a biological cell membrane, PD-L1 protein is expressed on the surface of the cell membrane, and the immunosuppressant is wrapped in the cell membrane nano-vesicle. PD-L1 protein can be expressed on the surface of a cell membrane; the PD-L1 protein can be combined with PD-1 on the surface of a T cell and activate a PD-1/PD-L1 immune checkpoint signal axis; meanwhile, the PD-L1 cell membrane nano-vesicle is used as a targeted drug delivery system for loading the immunosuppressant, and the wrapped immunosuppressant is brought to effector T cells expressed by PD-1 to play a role so that the transmission of immunosuppressive drugs to target tissues is enhanced; through combined application of PD-1/PD-L1 and an immunosuppressant double immune tolerance mechanism to T cells, in-vivo immunological rejection is significantly inhibited, the immunotherapy effect is improved, meanwhile, the dosage of the immunosuppressant is reduced, and the toxicity of the immunosuppressant is reduced.

The invention provides an immunogen composition containing polypeptide derived from cytomegalovirus (CMV) and a use method thereof. The composition comprises (a) at least one of CMV pp65 and polypeptide derived from CMV IE-1 polypeptide; and (b) polypeptide selected from groups formed by polypeptides derived from CMV VGLB, CMV VPAP and CMV p100 polypeptides, and the combination thereof. The immunogen composition of the invention can effectively activate CMV resistant immunoreaction after confirmation. Live virus, cells infected by CMV, and full-length CMV cells are not used in a polypeptide library so that no infection, mmunosuppression action, immunologic tolerance and the like are caused.

The invention provides application of decidua NK cells and decidua NK cell exosomes from cell subsets in preparing drugs and auxiliary therapeutic agents for treating diseases related to infertility.Experiments prove that the exosomes treat endometrium growth disorders by promoting endometrial thickness increasing, improving endometrial cell activity, reducing endometrial cell damage, promoting VEGF expression, maintaining stem features of endometrium matrix cells and stimulating proliferation, so that the pregnancy success rate of endometrium damage model mice is increased to 50-70% from 20%; and the exosomes treat diseases related to maternal-fetal immunologic tolerance disorders by playing a role of immunologic tolerance, reducing a spontaneous abortion rate and improving a help T lymphocyte level. Besides, the exosomes can effectively increase the developmental rate of zygotes fertilized no matter in vitro or in vivo in a multiple mode, meanwhile, an in-vitro fertilization rate, an implantation rate of implantation and a birth rate are also increased, and positive assisting effects on infertility treatment are achieved.

The present invention relates to the use of glycogen synthase kinase 3(GSK3) inhibitors, especially inhibitors of GSK-3α, GSK-3β and GSK-3β2, preferably, inhibitors of GSK-3β, in patients having autoimmune diseases and/or immune dysfunction/dysregulation to induce immune tolerance. Inhibition of GSK leads to activation of a pathway of dendritic cell maturation which leads to a dendritic phenotype which attenuates, rather than induces, immune responses. The immune responses and mature dendritic cells produced by the method of the present invention redirect or attenuate the immune response in individuals, thus leading to effective therapies for a number of autoimmune diseases and/or diseases of immune dysfunction/dysregulation (immune inflammatory diseases), including systemic lupus erythematosus (SLE), autoimmune diabetes (type I diabetes mellitus), asthma, rheumatoid arthritis, inflammatory bowel disease, among numerous others.

The invention discloses a reinforced learning algorithm based on an immunologic tolerance mechanism. The reinforced learning algorithm based on the immunologic tolerance mechanism comprises the steps of firstly designing the vector quantity of a primary function and the vector quantity of a weight value of a TD (lambda), then encoding the vector quantity of the weight value according to the number of floating points, when the error between the environment of a system and the real environment is larger than a set threshold value, regarding the environment of the system as a primary response in an artificial immune system, when meeting the environment for the first time, optimizing the environment by the immunologic tolerance mechanism, memorizing environmental knowledge by a memory, namely an immune body, then selecting the optimal strategy according to parameters of a current system, updating the parameters of the system according to a feedback reward value (r), continuously carrying out an iteration for the next time, when the error between the environment of the system and the real environment is smaller than the threshold value, regarding the environment of the system as similar environment, regarding the similar environment as a secondary response in the artificial immune system, and directly selecting the optimal strategy according to parameters of the system through the fact that the system judges motion selection.

Methods of inducing immune tolerance by administering an immunosuppressive agent and a compound represented by Formula (I) are disclosed:

Additionally methods of suppressing an immune response by administering an immunosuppressive agent and a compound represented by Formula (I) are disclosed. Further disclosed are methods for treating autoimmune diseases by administering an immunosuppressive agent and a compound represented by Formula (I). The variables of Formula (I) are described herein.

The invention relates to a veterinary Chinese medicinal composition for improving growth performance and enhancing nonspecific immunologic function of an organism. The composition is prepared from root of Chinese pulsatilla, astragalus, bighead atractylodes rhizome, isatis root, baikal skullcap root, root of Chinese thorowax and rhubarb serving as raw materials. The invention also relates to a veterinary medicament prepared from the veterinary Chinese medicinal composition, a preparation method for the veterinary medicament and application of the veterinary Chinese medicinal composition. The veterinary Chinese medicinal composition of the invention has the effects of strengthening the body resistance to eliminate pathogenic factors, clearing away heat and toxic material and enhancing the nonspecific immunologic function of the organism, and can treat various atypical disease symptoms caused by low immunologic function of the organism, immunologic tolerance, endogenous toxin, stress and the like, the reduction in the growth performance and damp-heat disease symptoms such as wind-heat type cold, flu, bursa of fabricius, intestinal disease syndromes and the like.

The invention belongs to the field of biomedicine, and particularly relates to a method for constructing a chronic transfection model of a hepatitis B virus. The method disclosed by the invention comprises the following steps: transfecting HBV (hepatitis B virus) plasmids into a model-preparing experimental mouse (preferably adopting male C3H/HeN of 4-8-week old), and constructing the chronic transfection model of the HBV. The chronic transfection model of the hepatitis B virus constructed by the method can be used for researching specific action mechanism of single or multiple genes in an HBV pathogenic process; transgenic modification of the mouse is not needed; the method is free of limitations such as immunologic tolerance, easy to obtain, and low in cost; the problem of long-term shortage of an animal model suitable for the HBV in related technical fields can be solved; and a good animal model is provided for further research on life history and chronic mechanism of the HBV and screening of vaccines and new medicines.

Methods and compositions to reduce immunogenicity of proteins are disclosed. Compositions comprising therapeutic proteins (such as Factor VIII or any other protein or peptide) complexed with liposomes comprising PS and PC (PS liposomes), or comprising PS, PI and PC and, optionally, cholesterol (PS/PI liposomes) may be used.

The invention relates to an immunomicrosphere for overcoming B cell immunological tolerance and application thereof. The immunomicrosphere comprises a microsphere medium, wherein the outside of the microsphere medium is coated with vaccine antigen, and the inside of the microsphere medium is coated with immune carrier protein for activating T cells. The invention also relates to application of the immunomicrosphere for overcoming the B cell immunological tolerance in preparing vaccines and immunological adjuvants. By using the technical scheme, the immunomicrosphere is combined with B cell receptor through the antigen and phagocytized by B cells, and the carrier protein is released and degraded in the cells; the immunomicrosphere is presented to Th cells through B cell MHC II to activate the TH cells to release cell factors, thereby promoting the activation and proliferation of the B cells; and high-titer antibody is generated through the affinity maturation process. The antigen protein and the immune carrier protein are respectively arranged on the surface of the microsphere and inside the microsphere, thereby preventing the antigen protein epitope and the Th cell activation epitope from competing with the B cell receptor.

The present invention discloses one kind of recombinant human insulin and its coding gene and application. The recombinant human insulin is following protein: 1. the protein comprising the amino acid residue sequence of Sequence 1 in the sequence list; and 2. the derivative protein with the sequence of Sequence 1 through the substitution, deletion and/or addition of amino acid residue(s) and possessing the function of human insulin. The recombinant human insulin has a connecting peptide introduced into the chain A and B sequences of natural insulin to favor to forming beta angle structure, a spatial structure similar to that of natural insulin and insulin activity. The present invention also provides one kind of engineering lactic acid bacteria with the recombinant human insulin gene and capable of surviving in intestinal tract for over 48 hr to stimulate the immune system of NOD mouse to generate specific recombinant human insulin antibody, raise the IL-4 level and induce immunologic tolerance generation.

The invention discloses a Mn-based degradable MOF nano-reactor and a preparation method and application thereof, the nano-reactor comprises an inner core Mn-based MOF nano-particle, the surface of the inner core Mn-based MOF nano-particle is functionalized and grafted with a pH responsive shell copolymer PEG-CDM-PEI, and the Mn-based MOF nano-particle is loaded with a biological enzyme GOx and an IDO immunosuppressor. The pH/ROS dual-responsive MOF nanoreactor drug controlled release system co-loaded with an immune checkpoint IDO inhibitor 1-MT and GOx is prepared by utilizing the advantages of high loading capacity, enzyme reaction space limitation, ROS responsive degradability and the like of an MOF nanoreactor, and tumor hunger/oxidation/IDO immune combined therapy is regulated and controlled. The drug-controlled system can respond to a weakly acidic tumor microenvironment, induce size reduction/charge reversal, overcome in-vivo tumor permeation and cell barrier, and improve the delivery efficiency; in addition, the self-enhanced MOF degradation and drug release performance is achieved; moreover, the immune therapy mediated by the drug control system can effectively inhibit the immune tolerance, enhance the anti-tumor immune response of the body and inhibit the growth, metastasis and relapse of tumors.

The present invention proposes the preparation of one kind of individual antitumor specific antibodys and its application in medicine preparation for tumor guide treatment and positioning diagnosis. The antibody preparing process includes three steps of inducing animal's immune tolerance, immunizing animal and extracting antibody. It is featured by that the health tissue cell of tumor patient is first used to induce animal's immune tolerance, and after the animal immune function becomes mature, the tumor cell of tumor patient is then used to immunize animal so as to prepare antitumor specific antibody.

A high-specificity recombinant immunotoxin for preventing and treating autoimmunopathy, rejection reaction and tumors is prepared from IL-18 as target moleculae and the actigve fragment PE38 of pseudomonas aeruginosa's exotoxin through configuring recombinant plasmid, preparing engineering bacteria transfected by said plasmid, expressing immunotoxin IL-18-PE38 and purifying. Its advantage is hightarget kill to TH1 cells.