66 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.

The present disclosure provides methods inducing immune tolerance in a human, comprising administering to the human an effective amount of a composition or a chimeric protein comprising a clotting factor and an Fc region.

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.

To provide compositions and improved methods for producing antigen-binding proteins (e.g., antibodies) that bind an epitope on a foreign target antigen of interest (e.g., a human target antigen of interest) that shares the epitope with a self-antigen or is homologous to the self-antigen.SOLUTION: Methods according to the present invention comprise reducing tolerance of the foreign antigen in non-human animals such as rodents (e.g., mice or rats) (optionally comprising in their germline humanized immunoglobulin heavy and / or light chain loci) by employing two or more guide RNAs (gRNAs) to create paired double-strand breaks at different sites within a single target genomic locus.SELECTED DRAWING: Figure 3

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.

Provided herein are methods of inducing immune tolerance to graft cells in a human patient in need thereof comprising administering to the patient (i) the graft cells. (ii) a chimeric FasL protein conjugated to a hydrogel, and (iii) transient sirolimus.

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.

Compositions and methods for inducing immune tolerance to proteins and subsequence administration of the proteins are disclosed. Compositions comprise proteins complexed with liposomes comprising PS and PC, wherein at least part of the PS is present as lyso-PS.

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.

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).

PEPTIDE CONJUGATES AND THEIR USE FOR PROMOTING IMMUNOTOLERANCY TO CAS NUCLEASES IN GENOME ENGINEERING GENE THERAPY The present invention relates generally to the field of medicine. More particularly, it relates to polypeptide conjugates, compositions, and methods for promoting immunotolerance to the CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein) system, for gene therapy by genome engineering. (No figure)

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.

To provide pharmaceutical compositions for osteoarthritis treatment, comprising immune-tolerized fetal stem cell-derived extracellular vesicles containing various components that promote hyaline cartilage regeneration and relieve inflammation at higher levels than those stem cell-derived extracellular vesicles obtained under general culture conditions, and thus exhibiting superior hyaline cartilage regeneration and anti-inflammatory efficacy as well as methods for manufacturing the extracellular vesicles and compositions for osteoarthritis treatment using the extracellular vesicles.SOLUTION: These extracellular vesicles derived from immune-tolerized fetal stem cells contain fibroblast growth factor-2 (FGF-2), fibroblast growth factor-7 (FGF-7), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta 1 (TGF-β1), bone morphogenetic protein-4 (BMP-4), bone morphogenetic protein-5 (BMP-5), and bone morphogenetic protein-7 (BMP-7) and HLA-G protein.SELECTED DRAWING: Figure 1

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 invention discloses application of CD52 protein in preparation of a medicine for treating recurrent abortion, and belongs to the technical field of biological medicine. It is found that the CD52 protein can inhibit abnormal activation of maternal-fetal interfacial effect T cells in a targeted mode and reduce release of proinflammatory factors (such as IFN-gamma), so that immune tolerance imbalance is reversed, and the pregnancy outcome is improved. The CD52 protein is applied to treatment of the recurrent abortion for the first time, and the CD52 protein has the advantages of being high in targeting performance and high in safety.

The invention provides application of a human beta-defensin-1 combined alphaPD-1 antibody in preparation of immunomodulatory drugs for treating or preventing colon cancer, and relates to the technical field of biological medicines, the regulation effect of the human beta-defensin-1 combined alphaPD-1 antibody on immune cells is observed in in-vivo experiments, TNF-alpha + CD8 + T and IL-2 + CD8 + T can be reduced, INF-gamma + CD8 + T and alphaPD-1 + CD8 + T cells are obviously improved, and the immunomodulatory effect of the human beta-defensin-1 combined alphaPD-1 antibody on the colon cancer is improved. The invention provides a new thought and approach for the application of the human beta defensin-1 combined alphaPD-1 antibody in anti-tumor immunity, and particularly improves the immune tolerance generated by single alphaPD-1 antibody treatment and promotes the infiltration of CD8 + T into tumors.

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 present disclosure is related to compositions and systems for inducing immune tolerance for transplanted cells, organ, or tissues in a transplant recipient. Also provided herein are methods of making and methods of administering tolerizing vaccines / regimen or preparatory regimens.