151 results about "Immunologic Tolerance" patented technology

The present invention relates generally to the field of generating fusion proteins to be used in cancer therapy, and more specifically, to nucleotide sequences encoding the fusion proteins, wherein the chimeric fusion proteins comprises at least one targeting moiety and at least one immunomodulatory moiety that counteracts the immune tolerance of cancer cells.

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 present invention is based on the discovery antigen-presenting cells (APCs) may be generated to have predetermined levels of expression of the intracellular enzyme, indoleamine 2,3-dioxygenase (IDO). Because expression of high levels of IDO is correlated with a reduced ability to stimulate T cell responses and an enhanced ability to induce immunologic tolerance, APCs having high levels of IDO may be used to increase tolerance in the immune system, as for example in transplant therapy or treatment of autoimmune disorders. For example, APCs having high levels of IDO, and expressing or loaded with at least one antigen from a donor tissue may be used to increase tolerance of the recipient to the donor's tissue. Alternatively, APCs having reduced levels of IDO expression and expressing or loaded with at least one antigen from a cancer or infectious pathogen may be used as vaccines to promote T cell responses and increase immunity.

The present invention is based on the discovery antigen-presenting cells (APCs) may be generated to have predetermined levels of expression of the intracellular enzyme, indoleamine 2,3-dioxygenase (IDO). Because expression of high levels of IDO is correlated with a reduced ability to stimulate T cell responses and an enhanced ability to induce immunologic tolerance, APCs having high levels of IDO may be used to increase tolerance in the immune system, as for example in transplant therapy or treatment of autoimmune disorders. For example, APCs having high levels of IDO, and expressing or loaded with at least one antigen from a donor tissue may be used to increase tolerance of the recipient to the donor's tissue. Alternatively, APCs having reduced levels of IDO expression and expressing or loaded with at least one antigen from a cancer or infectious pathogen may be used as vaccines to promote T cell responses and increase immunity.

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.

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

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 invention discloses an immunologic tolerance dendritic cell, a preparation method thereof and a special culture medium. The culture medium is formed by the way that mesenchyma stem cells are added into a dendritic cell culture medium. The preparation method comprises: the precursors and the inducible factors of dendritic cells are added into the culture medium. The co-culture proportion of the mesenchyma stem cells to the dendritic cells is (1-2) to (1-10), preferably 1 to 1; the precursors of the dendritic cells are CD34 cells; and the inducible factors comprise GM-CSF, TNF- alpha, IL-4 and LPS. The invention provides the application of the immunologic tolerance dendritic cell during preparing immunologic tolerance medicine for organisms. The immunologic tolerance dendritic cell can lowly express co-stimulatory molecule, reduce inflammatory factors, increase the secretion of suppressor cytokines, have vasculogenesis activity, and inhibit the multiplication of variant T cells. The invention has the advantages of simple operation, convenience and practicality, and establishes a stable culture technical system for selective activation dendritic cells.

The invention discloses a building method for autovaccine in-vivo induced by aiming at human TNF(Tumor Necrosis Factor)-alpha molecule. With a step-by-step cloning method, a fusion gene of hTNF-TT830-844, hTNF-HEL46-61 and hTNF-PADRE is built; point mutation (T439-A,C440-G) is introduced into a natural human TNF gene to optimize a mRNA (Ribonucleic Acid) secondary structure; the fusion gene is cloned into a pET22b prokaryotic expression vector, and efficient expression is achieved in the bacterial strain of escherichia coli; three T accessory cell epitope peptides are introduced between the epitope peptide structure domains of hTNF by the computer-aided analysis and is fused with the hTNF-alpha to overcome the immunological tolerance of an organism for the autologous protein, and therefore the organism generates high-level humoral immune response; the generated high-level hTNF-alpha neutralizing polyclone antibody can neutralize killing activity of the hTNF-alpha on L929 cells in vitro; the hTNF-PADRE has the strongest immunogenicity; the high-level antibody can be induced under the condition of using no immunological adjuvant; and the vaccine has favorable protection and curing action on mouse models suffering from rheumatoid arthritis induced by the II-type collagen, cachexia and the like induced by LPS (lipopolysaccharide).

This invention relates to a therapeutic molecule capable of suppressing an immune response against an organ or tissue transplantation in a patient. In particular, the invention relates to a conjugate comprising a first portion connected to a second portion, wherein the first portion binds to an MHC Class I molecule and the second portion has HLA-G activity. This conjugate may be used as a medicament to modulate immune responses and induce immunological tolerance specific to allogenic MHC complexes.

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.

An object of the present invention is to provide a regulatory dendritic cell inducing agent applicable to the treatment of immune disease as well as an immune tolerance inducing agent such as a preventive and / or therapeutic agent for allergic disease and a preventive and / or therapeutic agent for autoimmune disease, both of which are safe and have the mechanism of action different from that of conventional drugs. As a means for achieving the above object, an immune tolerance inducing agent comprising 5-aminolevulinic acid (ALA) or a derivative thereof, or a salt of the 5-ALA or the derivative and an iron compound as active ingredients is prepared. Preferable examples of the ALAs can include ALA and various esters such as methyl ester, ethyl ester, propyl ester, butyl ester, and pentyl ester of ALA, and their hydrochlorides, phosphates, and sulfates. Preferable examples of the iron compound can include sodium ferrous citrate.

The invention provides multifunctional antibody-ligand traps and methods of using them to counteract immune tolerance and / or immune dysfunction. The multifunctional antibody-ligand traps and fusion proteins of the invention can counteract immune dysfunction in order to restore and unleash antitumor or pathogen-directed immune responses. Provided here are promising immunotherapeutic agents for treatment and prevention of cancers, infectious diseases, and immuno-inflammatory disorders.

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 present invention provides methods for producing antibodies against peptides, proteins, or such to which immune tolerance is easily established, by using antigen-binding molecules comprising a domain that binds to a molecule expressed on the surface of a cell having an immune response-suppressing function and a T cell receptor (TCR) complex-binding domain. The present invention also provides pharmaceutical compositions for use in combination with therapeutic vaccines and agents for enhancing a humoral immune response, each comprising the antigen-binding molecules as active ingredients.

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.

Disclosed are therapeutic formulations comprising myristoylCoA and N-myristoyl transferase and methods of using such formulations to stimulate the immune system of a mammal afflicted with carcinoma and having a detectable blood level of unacylated A-protein to produce an immune response thereto. Also disclosed are methods of treating an A-protein displaying carcinoma in a mammal.

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.