45 results about "Immunologic Tolerance" patented technology

The invention belongs to the field of antibody development, and discloses a screening method and application of a human-mouse protein high homologous target antibody based on a fully humanized antibody mouse. Aiming at the problem of weak antibody response caused by immune tolerance of human-mouse high homologous targets (protein homology is greater than or equal to 95%), the following scheme is provided: in embryonic stem cells (ES cells) of HUGO-Mabfully humanized antibody transgenic mice, a mouse target gene (such as ACVR2A) is knocked out through a Turbo Knockout technology, and homozygous knockout ES clones are screened; carrying out microinjection on the clones to the whitened B6 mouse blastocyst, and transplanting a pregnant mouse to obtain a Founder mouse; the Founder mouse is subjected to target antigen immunization for more than or equal to 4 times (the Freund's complete adjuvant is used for the first time), and the titer of the serum antibody is detected. According to the invention, 100% homozygous knockout chimeric efficiency is realized in the Founder stage, the mouse construction period is shortened from traditional 8-10 months to 3-4 months, and the diversity and affinity of the antibody are significantly improved (titer reaches 1: 729,000). The obtained antibody can be used for preparing medicines for treating tumors or autoimmune diseases.

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 belongs to the technical field of biological medicines, and particularly discloses a pH and ultrasound double-response type oncolytic microorganism as well as a preparation method and application thereof. On the basis of a tumor targeting platform, a mild thermal response gene loop expression GM-CSF and a surface-coated oncolytic microbial system are integrated, chemotherapeutic drugs are released in a tumor core area, and immunogenic cell death is induced. A thermal response loop is accurately activated through low-intensity focused ultrasound, and engineering bacteria are promoted to express GM-CSF and secrete a large amount of mannose modified OMVs. Due to the nanometer size and mannose targeting of the OMVs, the OMVs are efficiently enriched in lymph nodes, the OMVs are reprogrammed into an immune activation state from an immune tolerance state, and the OMVs and ICD cooperate to promote dendritic cell maturation, tumor antigen presentation and activation of tumor killer T cells, so that a remarkable and powerful treatment effect is achieved in various tumor models, and the application prospect is wide. A new strategy is provided for remodeling the lymph node immune microenvironment and enhancing the anti-tumor immune response.

Provided are compositions and methods for reducing pre-existing antibodies against viral vector or gene-editing related proteins. The compositions showed reduction in various antibody titers by administration of a liposome composition complexed with a protein or fragment thereof of a viral vector. The liposomes comprise phosphatidylcholine and phosphatidylserine, wherein some or all of the PS is present as lyso-PS. The compositions and methods can be used in conjunction with gene therapy and nucleic acid based vector based vaccinations and therapeutics.

The present invention provides intravenous pharmaceutical compositions comprising engineered plant virus-based nanoparticles for the treatment or prevention of autoimmune conditions. The nanoparticles display immunodominant peptides that induce immune tolerance in a subject when administered intravenously. The invention further provides methods of manufacturing virus-based nanoparticles, including production in plant expression systems and optional viral inactivation, to render them suitable for therapeutic use in mammals. Also provided are methods of intravenous administration of the pharmaceutical compositions to a subject in need thereof for treating or preventing autoimmune conditions.

The application discloses application of CD52 protein in preparation of a medicine for treating recurrent spontaneous abortion, and belongs to the technical field of biological medicine. It is found that the CD52 protein can target and inhibit abnormal activation of effector T cells at a maternal-fetal interface, reduce release of proinflammatory factors (such as IFN-gamma), thereby reversing immune tolerance imbalance and improving pregnancy outcome. The CD52 protein is applied to the treatment of recurrent spontaneous abortion for the first time, and has the advantages of high targeting and high safety.

The invention relates to the technical field of prevention and treatment of complications after organ transplantation, and discloses a preparation for preventing and treating diabetes mellitus after organ transplantation based on a Treg cell metabolic regulation function and application, the preparation takes repair or enhancement of the Treg cell metabolic regulation function as a core action mechanism, and comprises at least one active component, according to the PTDM prevention and treatment preparation based on the Treg cell metabolic regulation function and the application, the preparation contains IL-2 / anti-CD3 / CD28 beads, FKBP12siRNA, a PPAR-gamma agonist, SOCS-3siRNA and other active ingredients, and the active ingredients are matched with pharmaceutical auxiliary materials to be prepared into an injection or a freeze-dried powder injection; the preparation is suitable for PTDM high-risk recipients using CNI after kidney / heart transplantation, has a single drug and combination scheme, can also amplify Treg cells in vitro for transfusion to assist intervention, can realize'immune tolerance-metabolic regulation 'double-effect synergy, accurately target PTDM key pathways, adapt to multiple transplantation types, and can be combined with CPB for blood perfusion to synergistically reduce PTDM and AKI risks, reduce non-target injury and improve the curative effect of the PTDM. The life quality of a recipient is improved, the medical burden is reduced, and the blank of PTDM immunotherapy is filled.

This invention discloses a traditional Chinese medicine composition for treating allergic rhinitis and its application, relating to the field of allergic rhinitis treatment technology. It comprises: 12-18 parts Astragalus membranaceus, 8-12 parts Codonopsis pilosula, 6-10 parts medicated leaven (processed with styrax), 5-9 parts Lilium brownii, 5-10 parts Platycodon grandiflorus, 4-7 parts Prunus mume, 3-5 parts Cicadae periostracum, 2-4 parts Xanthium sibiricum (processed with styrax), and 2-4 parts Glycyrrhiza uralensis (processed with styrax). This invention scientifically combines Astragalus membranaceus and Codonopsis pilosula (for invigorating qi and strengthening the exterior), Xanthium sibiricum (processed with styrax) and Cicadae periostracum (for dispelling wind and opening the orifices), Lilium brownii and Prunus mume (for astringing the lungs and nourishing the blood), medicated leaven (processed with styrax) for strengthening the spleen and harmonizing the middle jiao, and Platycodon grandiflorus and Glycyrrhiza uralensis (processed with styrax) for harmonizing the various herbs. The proportions of each group can produce a synergistic effect, which can not only effectively relieve the external symptoms of allergic rhinitis such as nasal congestion, runny nose, sneezing, and nasal itching, but also improve the patient's allergic constitution and enhance immune tolerance by invigorating qi and strengthening the exterior, regulating lung and spleen functions, thereby reducing the recurrence rate and achieving a therapeutic effect that addresses both the symptoms and the root cause of allergic rhinitis.

The invention relates to the technical field of cellular immunotherapy, and discloses an application of a CD74 positive regulatory T cell in treatment of graft versus host disease, the CD74 positive regulatory T cell is composed of the following components in proportion: in a sorted and purified cell population, the proportion of regulatory T cells with CD4 + CD25 + CD127-phenotype is 85-95%, the proportion of regulatory T cells with CD25 + CD127-phenotype is 1-5%, and the proportion of regulatory T cells with CD24 + CD25 + CD127-phenotype is 1-5%. Wherein the CD74 high-expression subgroup accounts for 60-75% of the total amount of the regulatory T cell, the cell subgroup functional immune molecule combination comprises CTLA4, FOXP3, TIGIT and TNFRSF18, when the CD74 positive regulatory T cell is used for treating graft versus host disease, the CD74 positive regulatory T cell is firstly used for preventive infusion, single infusion is performed on the day of transplantation, the dosage is 5 * 10 < 5 > cells / receptor, and then the CD74 positive regulatory T cell is used for treating the graft versus host disease. The CD74 positive regulatory T cells are used for repeated therapeutic infusion when early aGVHD symptoms occur, graded treatment is carried out, pathological immune response is inhibited to the maximum extent, immune tolerance is promoted, the treatment is carried out once a week and 2-3 times in total, and the dosage of each time is 1 * 10 < 6 > cells / receptor.

The present application relates to the use of ZNF683 as a target in the diagnosis or therapeutic prognosis monitoring, and treatment of diseases related to the regulation of T cell immune tolerance. In particular, the present application studies the regulatory effect of ZNF683 on human primary T cells, and tests the feasibility of ZNF683 as a target for the prognosis and treatment of GVHD after clinical transplantation.

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).

The invention belongs to the technical field of medicine application and biological medicine, and particularly relates to application of an AKT inhibitor in preparation of a medicine for inducing pancreas islet transplantation immune tolerance. The invention discovers that the AKT inhibitor MK-2206 can effectively induce immune tolerance after pancreas islet transplantation for the first time, system experiments prove that a short-term intervention scheme adopting the AKT inhibitor MK-2206 can obviously promote long-term survival of pancreas islet transplantation, and the effect of the AKT inhibitor MK-2206 is superior to that of a traditional immunosuppressor. The method belongs to secondary development of medicines with known active ingredients, and provides a potential novel treatment strategy for clinical induction of transplantation immune tolerance.

Provided are methods of making a chimeric thymus in a subject, including implanting a donor thymic functional unit tissue graft, wherein the donor thymic functional unit tissue graft includes thymic epithelial cells (TEC) and dendritic cells. The chimeric thymus is useful to induce a dual immunologic tolerance to both donor tissue antigens and tissue antigens of the subject.

Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes comprising two or more of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASG or FasL, Ccl21 or Ccl21b, MfgeS and Serpin B9 or Spi6, that shield the cells from immune surveillance (ie. “cloaking genes”). The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen.

Provided herein are compositions and methods for the treatment of allergy, such as food allergy. Also provided herein are compositions and methods for modulating an immune response associated with allergy and / or inducing immune tolerance or desensitization to an allergy, such as a food allergy.

The present disclosure provides compositions comprising mannose-fused antigens to target mannose receptors. The compositions may be used to prevent immunity or reduce an immune response protein-based drugs that would otherwise elicit an immune response.

The present invention provides a composition for preventing hair loss or promoting hair growth, the composition comprising a culture of immune-tolerant dendritic cells as an active ingredient.

An immunogenic composition that includes an adjuvant and a soluble protein. The adjuvant may be a nanoparticle, such as a zinc chitosan nanoparticle. The soluble protein may comprise a tag, such as a His tag. A method for inducing an immune response in a subject in need thereof, breaking an immune tolerance in a subject in need thereof, and / or for active immunization to prevent a disease in a subject by administering the immunogenic composition. A system for inducing an immune response in a subject in need thereof, breaking an immune tolerance in a subject in need thereof, and / or for active immunization to prevent a disease in a subject that includes the immunogenic composition and a delivery system.

The application relates to a preparation of a galactose detection kit by using a chemiluminescence immunoassay technique. Since the galactose has small molecular weight, poor immunogenicity, strong immunological tolerance, and has a D / L chiral structure, exists in a six-membered ring form in a solution, and can be converted into alpha and beta anomers. Therefore, when preparing a corresponding antibody, firstly, a suitable anomer and a derivative site need to be selected, and a derived hapten and a specific macromolecular carrier are coupled to prepare a complete antigen. The application successfully prepares an antibody with good specificity and strong affinity by designing and reforming the hapten. The application mainly relates to the design and synthesis of a galactose hapten, the preparation of a galactose complete antigen and an anti-galactose antibody, and a method for determining the concentration of galactose, the composition and ingredients of a reagent. The galactose derivative has the structure shown in formula (I).

This invention provides the use of spermidine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating autoimmune uveitis. The medicament is formulated as an oral or intraocular injection. The medicament is used to rebuild ocular immune tolerance by promoting autophagy flux activation and downregulating the expression of LCN2 protein in local tissues, inhibiting the differentiation of CD4+ T cells into Th17 cells and promoting their differentiation into Treg cells. Spermine exhibits significant efficacy and high safety in treating autoimmune uveitis.

The present disclosure provides a novel technique relating to immunological tolerance. More specifically, the present inventor found for the first time that, in a technique for inducing immunological tolerance by administering to an organ transplantation patient (a recipient) a cell preparation containing cells in which anergy is induced by an inhibitor inhibiting the interaction between CD80 / CD86 and CD28, the immunological tolerance continues even after the disappearance of the cells derived from the cell preparation from the recipient (infectious immunological tolerance). Further, the present inventor proved that such a cell preparation can elicit immunological tolerance against immunological rejection caused by allergy, iPS cells, etc. or cells, tissues or organs derived therefrom.

A recombinant vector, a lentivirus, a lung-exempt MSLN CAR-T cell, and an anti-tumor agent are provided. The recombinant vector includes a first nucleotide sequence, a second nucleotide sequence, and a third nucleotide sequence, the first nucleotide sequence encodes a mesothelin (MSLN)-binding domain, the second nucleotide sequence encodes a leukocyte immunoglobulin-like receptor (LIR-1), and the third nucleotide sequence specifically binds to a lung-highly-expressed molecule. The lentivirus is constructed using the recombinant vector. The lung-exempt MSLN CAR-T cell is constructed using the recombinant vector or the lentivirus. When the lung-exempt MSLN CAR-T cell enters lung tissue, the second nucleotide sequence binds to the lung-highly-expressed molecule through the third nucleotide sequence, inhibiting the killing function of CAR-T to avoid pulmonary toxicity; when the lung-exempt MSLN CAR-T cell infiltrates tumor tissue, the second nucleotide sequence is inactivated, activating CAR-T cells to kill tumor cells, offering the advantages of precise therapy and low side effects.

The present disclosure provides, in part, methods of eliciting immuno-tolerance using truncated membrane-bound and soluble immune checkpoints. Constructs comprising the immune checkpoint protein or portions thereof capable of binding to and activating the immune checkpoint proteins receptor are provided. The nucleic acid encoding the immune checkpoint protein or portion thereof is operably connected to a promoter and optionally also a secretory signal to allow for secretion of the immune checkpoint protein or portion thereof. The constructs may include a viral vector which can be used to deliver or introduce the construct into a transplantable article or organ.

Described herein are FasL-engineered biomaterials, as well as methods of making and using such FasL-engineered biomaterials, such as for immunomodulation, such as for inducing immunosuppression and specific immune tolerance, such as for preventing or reducing the risks of rejection of cellular or tissue grafts and / or the treatment of autoimmune disorders such as Type I diabetes. In specific embodiments, the FasL-engineered biomaterials are biotinylated microgels bound to SA-FasL.

Methods for the detection of subjects at risk of developing rheumatoid arthritis, and subjects having early rheumatoid arthritis thus allowing for early intervention. Compositions for inducing immune tolerance in a subject thus treating or slowing progression of RA. Kits useful in the diagnosis of RA.

Disclosed herein are methods of producing a hypoimmune cell and methods of mediating localized immune tolerance.