105 results about "Graft rejection" patented technology

The invention discloses a monoclonal antibody targeting all CD45 subtypes and application of the monoclonal antibody, and belongs to the field of monoclonal antibody preparation. The hybridoma cell strain capable of stably secreting all anti-human CD45 subtype antibodies is successfully obtained by stably expressing short and long molecular subtypes of human CD45 extracellular regions in L929 mouse fibroblasts, immunizing BALB / c mice with L929 cells expressing the two molecular subtypes of human CD45, and fusing splenocytes with SP20 myeloma cells after the serum titer reaches the standard. And the monoclonal antibody targeting all subtypes of CD45 is obtained. The monoclonal antibody provided by the invention shows a high-affinity binding characteristic with all human CD45 molecular subtypes, has important application value in the aspect of human CD45 molecular detection, and can be used as a therapeutic antibody in the fields of tumor immunotherapy, autoimmune disease treatment, transplant rejection resistance and the like.

The art does not provide systematic and reproducible methods to personalize dosing of multiple immunosuppressive medications after transplantation. This invention provides a method to systematize multi-drug immuno suppression management in tissue and organ transplantation using an artificial intelligence-based complex systems approach. In embodiments of this invention, immunosuppression drug dose, blood drug concentrations, donor-derived fraction of cell free DNA (dd-cfDNA %), and aspartate aminotransferase are used to indicate allograft status or a proxy for allograft status, to generate a phenotypic response surface to produce individual treatment modalities and dosages using empirically determined unique coefficients. This surface is used to calculate appropriate immunosuppression drug doses associated with the desired outcome for that patient. Embodiments of this disclosure are directed to identifying optimized combinations of inputs for the complex system of the immunosuppressed transplant patient in order to avoid transplant rejection while avoiding unnecessary toxicity and maintaining a robust enough immune response to fight infection.

The present invention relates to double stranded oligonucleotides that are complementary to JAK1, leading to modulation of the expression of JAK1. Modulation of JAK1 expression is beneficial for a range of medical disorders including inflammatory bowel disease, organ transplant rejection, graft-versus-host disease, multiple sclerosis, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriasis, dermatitis, diabetic nephropathy, systemic lupus erythematosus (SLE), dry eye disease, cancer, myelofibrosis, and asthma. Also included are compositions comprising the double stranded oligonucleotide and methods of treatment using the double stranded oligonucleotide.

Provided herein are novel drug-linker conjugates and antibody-drug conjugates of imidazoquinoline amine derivatives, which have agonistic activities towards Toll-like receptors (TLRs), in particular TLR7 and / or TLR8, as well as pharmaceutical compositions and methods of treatment thereof for certain diseases or conditions mediated by or associated with TLR7 and / or TLR8 (e.g., graft rejection, autoimmunity, inflammation allergy, asthma, infection, sepsis, cancer and immunodeficiency).

The invention relates to a decellularized acellular dermal tissue prepared by supercritical fluid extraction. More specifically, the present invention relates to a cell-free dermal tissue having improved extracellular matrix retention levels and optimized mechanical properties (e.g., critical loading and elastic restoring force) by extraction using supercritical fluids. The acellular dermal tissue of the present invention is obtained by decellularization, is not treated with a surfactant, thus retains mechanical properties, does not have toxicity caused by a residual surfactant, and minimizes transplant rejection, and thus can be effectively used for treating a patient with damaged skin tissue.

This invention provides an antibody composition with improved stability, exhibiting reduced fragmentation of the antibody polypeptide chain during manufacturing and subsequent storage. [Solution] This disclosure relates to improved compositions and methods for treating T cell-mediated diseases and disorders (e.g., autoimmune disorders, graft-versus-host diseases, and graft rejection). Provided are antibody-containing anti-αβTCR binding polypeptides comprising at least one amino acid substitution or modification that enhances the stability of the binding polypeptide by reducing fragmentation of the light chain variable region. Methods provided herein generally involve administering an effective amount of a stabilized, humanized binding polypeptide specific to the alpha-beta T cell receptor (αβTCR) to a subject in need thereof.

The present disclosure relates to anti-human CD154 antibodies having a modified effector function. The present disclosure also relates to the use of these anti-human CD154 antibodies in the treatment of conditions associated with CD154 activation, the conditions associated with CD154 activation are, for example, transplant rejection, inflammatory conditions and diseases, dysfunctional immune responses associated with viral infections and diseases, autoimmune conditions and diseases, allergic conditions, atherosclerotic conditions, or neurodegenerative conditions and diseases. The present disclosure also relates to the use of these anti-human CD154 antibodies in inducing central tolerance and hematopoietic cell chimerism in transplanted patients.

The present invention provides novel drug-linker conjugates and antibody-drug conjugates of imidazo quinoline amine derivatives, which have agonistic activity against Toll-like receptors (TLRs), in particular TLR7 and / or TLR8, also provided are pharmaceutical compositions and methods of treatment against certain diseases or conditions mediated by or associated with TLR7 and / or TLR8 (e.g., graft rejection, autoimmunity, inflammation, allergy, asthma, infection, sepsis, cancer, and immunodeficiency).

The present disclosure provides a scalable and practical off-the-shelf allogeneic T cell therapy for treating cancer including employing a population of nonexhausted allogeneic virus specific CD4+ T cells, CD8+ T cells or CD4+ and CD8+ T cells that express a nonexhausted PD-1negTIGITnegTCF-1High TOXLo early stem cell TSCM phenotype. The virus-specific population of CD4+ T cells, CD8+ T cells or CD4+ and CD8+ T cells that expresses the nonexhausted early stem cell TSCM phenotype and comprises TCRs specific for a protein of a virus is genetically modified to stably express up to three chimeric antigen-receptors (CARs). Each CAR is specific for a cancer antigen. At least one of the CARs comprises a CD30 CAR expressing a CD30-specific scFv fragment, and / or a chimeric alloimmune defense receptor (ADR); and / or a chimeric HLA accessory receptor fused with a cytolytic endodomain of the T cell receptor zeta chain, thereby reducing risk of host versus graft rejection (HVGR). In some regimens, multiple populations of cells can be combined and co-infused as the off the shelf T cell therapies.

In the various aspects and embodiments, the present disclosure provides cell populations or cell "banks" thereof to provide immune compatible, allogeneic cell therapies. In the various aspects and embodiments, the cell populations and progeny thereof maintain sufficient HLA Class I and HLA Class II functionalities, while facilitating patient matching to prevent or reduce graft versus host disease (GVHD) or graft rejection. The disclosure further provides methods for creating the populations by gene editing, and methods for cell therapy involving cells or tissues derived from the cell populations (including but not limited to hematopoietic stem cells, or "HSCs", progenitors, or progenies thereof).

This invention relates to methods and compositions for assessing risk by measuring total and specific cell-free nucleic acids (such as DNA) in a subject. The methods and compositions provided herein can be used to determine risk of a condition, such as transplant rejection.

Provided is a modified regulatory T cell capable of recognizing cells of the liver, capable of treating and / or preventing transplant rejection or immune-mediated damage, and capable of promoting regeneration of cells of the liver.SOLUTION: The present invention provides engineered regulatory T cells (Tregs) comprising a chimeric antigen receptor (CAR), wherein said CAR comprises an antigen recognition domain that specifically binds to the asialoglycoprotein receptor (ASGR). The invention also provides a method of promoting liver tissue repair and / or regeneration in a subject, said method comprising administering to said subject a modified Treg comprising a CAR, or a pharmaceutical composition comprising said modified Treg, wherein said CAR comprises a liver-specific antigen recognition domain.SELECTED DRAWING: None

The present invention discloses salts of a Compound 1:useful in the prophylaxis and / or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and / or disruption of cartilage homeostasis, congenital cartilage malformations, and / or diseases associated with hypersecretion of IL6 or interferons.

The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.

The present invention relates to the role of purinergic receptors and ATP in T cell activation and autocrine system signaling. In one embodiment, the present invention provides a method of preventing or treating diabetes by administering a therapeutically effective inhibitor of ATP to a subject. In another embodiment, the present invention provides a method of preventing or treating fibrosis by administering a P2X7R soluble fusion protein. In another embodiment, the present invention provides a method of preventing or treating graft rejection by administering an inhibitor of P2X receptor signaling.

Methods are provided for the preconditioning, conditioning, or rehabilitation of marginal organs to be used for organ or organ-derived cell transplantation. The methods of the present disclosure contact the marginal organs with a medium or perfusate comprising an effective dose of a Wnt agent. The Wnt agent reduces apoptosis of the cells in the marginal organ while also activating stem cells present in the marginal organ to promote repair, reconditioning, and / or regeneration of the marginal organ. Preconditioning or conditioning of the marginal organ with a Wnt agent reduces the risk of reperfusion injury. In some embodiments, preconditioning of the marginal organ reduces the risk of graft rejection when transplanted into an individual in need thereof.

A compound represented by formula (I) or a tautomer, optical isomer, deuterated substance, oxynitride, solvate, pharmaceutically acceptable salt or prodrug thereof can be used in preparing a pharmaceutical composition. The compound or the pharmaceutical composition can be used in the preparation a drug for the prevention and / or treatment of cancer, tumors, viral infections, depression, neurological disorders, trauma, age-related cataracts, organ transplant rejection or autoimmune diseases.

Provided is an immunomodulatory treatment composition for a transplantation disease through combined administration of a microbiome and an immunosuppressant. According to the present disclosure, it was confirmed that in an allogeneic transplantation cell model, combined administration of FK506 and the microbiome suppressed alloresponse and regulated the activity of T cells and B cells. Further, it was confirmed that in an acute graft-versus-host disease animal model, the combined administration reduced the disease activity, increased the probability of survival, and protected the tissue damage. In addition, it was confirmed that the combined administration improved transplantation rejection diseases by reducing the activity of Th1 and Th17 and increasing the activity of Tregs, and thus can be usefully used as an immunomodulator for transplantation rejection.

The present invention relates to a pharmaceutical combination comprising a first active ingredient, which is a CXCR3 antagonist 1-{(R)-2-(2-hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1, 2, 4] triazole-5-yl)-2-(3-methyl-[1, 2, 3] triazole-5-yl)-2-(3-methyl-[1, 2, 3] triazole-5-yl)-2-(3-methyl-[1, 2, 3] a second active ingredient (which is an anti-CD3 monoclonal antibody (mAb)) and a second active ingredient (which is an anti-CD3 monoclonal antibody (mAb)); the invention also relates to the application of the medicine combination in the prevention / prevention and / or treatment of (autoimmune) / inflammation-mediated conditions (including type 1 diabetes mellitus (T1D) (especially autoimmune T1D), multiple sclerosis, organ transplant rejection (especially kidney and heart allograft rejection), thyroid eye diseases, rheumatoid arthritis, ulcerative colitis, Crohn's disease, celiac disease, and the like), and also relates to the application of the medicine combination in the prevention / prevention and / or treatment of (autoimmune) / inflammation-mediated conditions (including type 1 diabetes mellitus (T1D) (especially autoimmune T1D), multiple sclerosis, organ transplant rejection (especially kidney and heart allograft rejection), thyroid eye diseases, rheumatoid arthritis, ulcerative colitis, Crohn's disease, celiac disease and the like. The traditional Chinese medicine composition can be used for treating psoriasis, atherosclerosis, psoriasis, lung inflammation and psoriatic arthritis

The present disclosure provides humanized and affinity mature antibodies (mAbs) and fragments thereof that specifically bind CD79 with high affinity. Anti-CD79mAb and fragments thereof are useful for the treatment of antibody-related disorders, including autoimmune diseases, allergy, transplant rejection, or immune-mediated rejection of therapeutic agents, optionally in combination with additional therapeutic agents. Furthermore, anti-CD79mAb and fragments thereof can be used for diagnostic purposes, including detection of CD79 cells in a biological sample and diagnosis of B-cell related diseases.

Provided herein are microfluidic arrays and miR panels useful in the identification of human subjects experiencing or at risk of experiencing an acute heart allograft rejection. Further provided are methods of identifying human subjects experiencing or at risk of experiencing an acute heart allograft rejection, including Acute Cellular Rejection (ACR) or antibody-mediated rejection (AMR). Further provided are system, apparatus, device, method and / or computer program product aspects, and / or combinations and sub-combinations thereof, for detecting an allograft rejection.

Clinical detection or diagnosis of transplant rejection currently utilizes various methods that rely on qualitative rather than quantitative data, or quantitative data that has low sensitivity and / or has a high rate of operator error. Provided herein are methods for identifying kidney transplant rejection in patents that is automated and consistent for the user. Further described herein are cut-offs for transplant biomarkers that relate to renal transplantation stability or rejection.

The invention relates to an anti-immunological rejection FK506 (at) ZIF-8 / HTCC ophthalmic gel and a preparation method thereof, FK506 and a zeolite imidazole skeleton (ZIF-8) are combined to prepare FK506 loaded nanoparticles (FK506 (at) ZIF-8), and quaternized chitosan is innovatively used as a sol of the FK506 (at) ZIF-8 to prepare the ophthalmic gel for use. The problems that a novel potent immune preparation tacrolimus administration mode is short in drug retention time, fast in metabolism, poor in cornea permeability and insoluble in water, and consequently the bioavailability of the FK506 eye drops is low are solved. Compared with an FK506 direct administration mode, the administration mode of the novel nanoparticle drug-loaded ophthalmic gel is higher in drug utilization rate, has a treatment effect on corneal transplantation immunological rejection, and delays the occurrence and development of transplantation rejection.

The invention discloses a chimeric receptor with an anti-transplant rejection function and an engineering cell for expressing the chimeric receptor, and further relates to a method for resisting tumors and transplant immunological rejection, in particular to a method for resisting NK cell immunological rejection. The invention also relates to cell therapy.

Disclosed herein, in some aspects, are compositions and methods for enhancing immunosuppressive functions of a cell, polynucleotides encoding polypeptides for effectuating the same, cells comprising the same, and compositions comprising the polypeptides, polynucleotides, and / or cells. In some aspects, the engineered cells show enhanced immunosuppression. Also disclosed are methods for disease treatment, such as graft-versushost disease, sepsis, transplant rejection, and / or autoimmune diseases, comprising administering engineered cells and / or compositions of the disclosure to a subject in need thereof.

Disclosed herein are computer-implemented systems, kits, and methods for determining the amount of contributor-derived nucleic acids in a biological sample from a graft recipient, the biological sample comprising nucleic acids from two or more genetically distinct contributors. The determined amount of contributor-derived nucleic acid can be used to monitor the status of a graft, for example, to assess the risk of graft rejection. In some examples, the two or more genetically distinct contributors may include the graft recipient, a fetus, and a graft donor. In some examples, the two or more genetically distinct contributors may include the graft recipient, a first graft donor, and a second graft donor. For example, the systems and methods determine an estimated percentage of the contributor-derived nucleic acids and / or an estimated percentage of fetal-derived nucleic acids.

The invention relates to a 5-aminohexahydro-6,7,8-trihydroxy-3H-oxazo-lo[3,4-a]pyridin-3-one (i.e. 2,3,4-trihydroxy-5N,6O-oxomethylidene-nojirimycin-1-amine) glycol-ipid mimetic derivative of formula (I) acting as antagonists or agonist of the TLR4 for the treatment and / or prevention of an immune disease such as e.g. acute inflammation, chronic disease allergy, the Metabolic Syndrome, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), immune mediated hepatitis, an autoimmune disease, graft rejection pathology, inflammatory bowel disease, atherosclerosis and airway hyperactivity, such as e.g. asthma and allergic rhinitis. An exemplary compound is e.g. example 1, compound (1).

Allogeneic kidney transplantation is a common transplant procedure and an optimal form of therapy for individuals who reach end-stage renal disease, significantly improving their quality of life, as compared to dialysis and supportive care. Nonetheless, its success relies on lifelong immunosuppression (IS), which causes serious complications. Moreover, despite immunosuppression (IS), around 8% of renal transplants will be rejected due to T cell-mediated and / or antibody-mediated reactions towards donor-specific allo-antigens. Importantly, scarce kidney recipients achieve an immunosuppressive drug-free tolerance, suggesting the existence of active tolerance mechanisms. Biomarkers to predict rejection risks and identify patients in which tolerance mechanisms could allow IS weaning, as well as a non-invasive biomarker to diagnose a rejection event, are highly needed to improve patient's care. The inventors identify circulating CD73+ DP8α Tregs or the expansion of CD73+ DP8α Tregs after transplantation as a non-invasive biomarker to predict rejection risks from 3 months post-transplantation. These data advocate for the potential value of these cells to improve kidney grafted patients' care through IS minimization and / or tolerance-inducing therapies. Strikingly, these results were observed in two independent cohorts, at 1-year post-transplantation. The present invention relates to a method of determining in a subject whether a subject has or is at a risk of developing transplant rejection comprising the steps of: i) determining the frequency of CD73-expressing DP8α Tregs among any T cell subset in particular among total CD3+ T cells or among total CD4+ T cells or among total CD8+ T cells in a sample obtained from the subject after transplantation, ii) comparing the frequencies determined at step i) with a predetermined reference value wherein detecting differential between the frequency of CD73- expressing DP8α Tregs among any T cell subset in particular among total CD3+ T cells or among total CD4+ T cells or among total CD8+ T cells determined at step i) and the predetermined reference value is indicative of whether a subject has or is at a risk of developing a transplant rejection.

The present invention provides a novel complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. Moreover, the present invention also provides a nucleic acid encoding such a complex, wherein the complex is a peptide or a protein. Such a nucleic acid may be comprised by a vector, and such a vector may be comprised by a host cell. In particular, compositions, such as a pharmaceutical compositions and vaccines are provided, which may be useful for example in the prevention and / or treatment of a diseases and / or a disorder including cancer, hematological disorders, infectious diseases, autoimmunity disorders and transplant rejections.

The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection.