17 results about "Tolerance induction" patented technology

A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and / or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

Disclosed in the present invention are a targeted immunotolerance vaccine, a preparation method therefor, and use thereof. The present invention separately modifies a rheumatoid arthritis-related autoantigen peptide and CTLA4 Ig with DSPE-PEG (DP) to prepare a targeted formulation DP-antigen peptide and a targeted formulation DP-CTLA4, which are then mixed to obtain the vaccine. The vaccine described in the present invention, after intravenous injection, binds to albumin in vivo by means of DSPE, "hitchhiking" on albumin to target and enrich in inflammatory lesions, the spleen, the liver, and other tolerance-inducing sites, inhibiting T cell activation, and inducing anergy and apoptosis of rheumatoid arthritis autoantigen-specific T cells, thereby achieving immunotolerance treatment and prevention of rheumatoid arthritis.

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Unlike historical controls, where 3BNC117 and 10-1074 expression is lost within the first 4-5 weeks, 2 macaques maintained 10-1074 expression and 1 macaque maintained 3BNC117 for the duration of the trial. Anti-3BNC117 antibodies were only observed in 2 of the 3 macaques and were significantly delayed. Anti-10-1074 antibody responses were a log lower than typically observed in historic controls. The use of hydroxychloroquine as a pretreatment for AAV inoculation is a promising strategy. The significant decrease in anti-10-1074 antibody levels and the successful delivery of 10-1074 in 2 macaques and 3BNC117 in 1 macaque was very encouraging. Extending the dosage of hydroxychloroquine beyond 3 doses may be sufficient to observe long-term bNAb expression in all animals and further decrease ADA responses. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.

The disclosure relates to the treatment, diagnosis and / or prevention of multiple sclerosis (MS) by using an immunodominant protein or peptide. More particular the invention relates to the field of antigen specific immunotherapies, such as the induction of tolerance.

The disclosure relates to the treatment, diagnosis and / or prevention of multiple sclerosis (MS) by using an immunodominant protein or peptide. More particular the invention relates to the field of antigen specific immunotherapies, such as the induction of tolerance.

A construction method of an immune tolerance induction scheme for orthotopic liver transplantation and an animal model thereof are provided, a design of the animal model is clever, reasonable, and has good repeatability, and the animal model meets requirements of rat orthotopic liver transplantation and is similar to human orthotopic liver transplantation. A postoperative survival rate is high, repeatability is good, and a tolerance rate is as high as 100%, which are confirmed by liver function testing and pathological analysis after operation, and the immune tolerance induction scheme can effectively solve problems of long time, high mortality rate, and high requirements for personnel and microscopy involved in research objectives and complete replication process of liver transplantation. An application of tolerance induction that can be extended to different combinations of other donors and receptors simultaneously.

Currently, there is no cure for myasthenia gravis (MG), and standard treatment focuses on symptom relief with the use of steroids or immunosuppressants, which have only temporary effects and are associated with serious side effects such as an increased risk of infection and death. [Solution] This application generally relates to compositions comprising tolerance-immunomodified particles encapsulating myasthenia gravis (MG)-related antigens, methods for treating MG using tolerance-immunomodified nanoparticles encapsulating MG-related antigens, and processes for preparing tolerance-immunomodified nanoparticles encapsulating MG antigens.

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.

The current disclosure describes compositions and methods that may be administered to prevent immune responses against therapeutic molecules. The disclosure provides for a composition comprising a polypeptide comprising an engineered Fms Related Receptor Tyrosine Kinase 3 Ligand (Flt3L) protein. Also described is a method of treatment comprising: administering to a subject in need thereof, an effective amount of an engineered Flt3L protein of the disclosure. Methods also relate to a method for inducing immunotolerance in a subject in need thereof comprising, the method comprising administering to the subject an engineered Flt3L protein of the disclosure.

Described are viral vectors, compositions, kits, and methods or using the vectors, compositions, kits to modulate immune response in a subject. The viral vectors include therapeutic recombinant adeno-associated viruses (rAAVs) and tolerance inducing gene therapy vectors. The therapeutic rAAVs and tolerance inducing gene therapy vectors can be used to deliver one or more therapeutic nucleic acids to the subject. The tolerance inducing gene therapy vectors induce immune-specific tolerance to the therapeutic rAAVs to improve efficacy of the therapeutic rAAVs and allow for multiple administrations of the therapeutic rAAVs with little or no associated immune response to the therapeutic rAAVs. The therapeutic rAAVs can be used to administer a therapeutic effect to the subject.

This plant stress tolerance inducer 1a comprises a compound 11 and a lipid 12. The compound 11 is at least one compound selected from the group consisting of nucleosides and modified nucleosides. The lipid 12 is at least one selected from the group consisting of fatty acids having 10-20 carbon atoms and acylglycerols including fatty acid residues having 10-20 carbon atoms.

The present disclosure relates to tolerance-inducing constructs for inducing tolerance, such as by targeting the tolerance-inducing construct to antigen presenting cells (APCs). Further disclosed are polynucleotides, vectors, host cells, pharmaceutical compositions and kits comprising said tolerance-inducing construct. Also disclosed are tolerance-inducing constructs and compositions for use in the treatment of immune disorders, such as in the prophylactic or therapeutic treatment of autoimmune diseases, allergic disease and graft rejection.

The invention provides a construction method of a recommendation model for individually adding an IS during low-dose immune tolerance induction treatment, equipment, a medium and a program product, and relates to the field of intelligent medical treatment. The method comprises the following steps: acquiring clinical data X, a treatment scheme T and a treatment result Y of a training set sample; training a filling model capable of predicting treatment results of different samples by using the clinical data and the treatment results; training a weighting model capable of predicting the treatment receiving possibility of different samples by using the clinical data and the treatment scheme; calculating a DR estimator based on the padding model and the weighting model; calculating a causal effect value according to the DR estimator; and training a regression model based on the clinical data and the causal effect value to obtain a recommendation model. According to the method, the recommendation model capable of helping the clinician to determine whether to add the IS individually during the ITI treatment period is established by utilizing causal reasoning and machine learning, and the judgment of the model and the judgment of the clinician have relatively satisfactory consistency.

Described herein are biomimetic Janus particles useful as artificial antigen presenting cells capable of activating T cells in vitro. “Bull's eye” ligand patterns mimicking either the native or reverse organization of the T cell immunological synapse are provided on the surface of nano- or micro-sized particles. Methods for activating T cells in vitro using biomimetic Janus particles described herein are also provided. T cells activated by the biomimetic Janus particles can be used in adoptive immunotherapies for treating cancer, tolerance induction in autoimmune disease, autologous immune enhancement therapy, and viral infection immunotherapy. Also described herein are methods for producing a biomimetic Janus particle.

The present invention relates to a pharmaceutical composition for inhibiting anticancer drug tolerance, recovering anticancer drug responsiveness, or enhancing anticancer drug sensitivity, the composition containing an ODC1 inhibitor as an active ingredient. More specifically, it was found that if ODC1 expression or activity is inhibited when inducing EGFR-targeting drug tolerance using a non-small cell lung cancer cell model overexpressing a kinase involved in EGFR-targeting drug tolerance induction and an animal model xenografted with same, the acquisition of EGFR-targeting drug tolerance caused by kinase overexpression is inhibited and the tolerance is alleviated, and thus drug responsiveness is recovered. Therefore, an agent that inhibits the ODC1 expression or activity can be effectively used as an effective ingredient in a pharmaceutical composition for inhibiting anticancer drug tolerance, recovering anticancer drug responsiveness, or enhancing anticancer drug sensitivity.

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.