41 results about "Graft rejection" patented technology

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 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).

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).

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.

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.

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.

Provided herein are methods and compositions for treating kidney-related disease conditions and complications, such as Berger's disease, and for preventing transplant rejection. For example, the present disclosure describes a method of improving function of a transplanted kidney in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds CD40 ligand.

The present disclosure relates to materials and methods for evaluation of transplant rejection in a subject. In particular. provided herein are synthetic scaffolds and methods of use thereof for early diagnosis of transplant rejection in a subject.

An antibody or antigen-binding fragment thereof that specifically binds to TNFR2 with high affinity is provided. The invention also provides a nucleic acid molecule for coding the antibody or the antigen binding fragment thereof, an expression vector and a host cell for expressing the antibody or the antigen binding fragment thereof, and a production method of the antibody or the antigen binding fragment thereof. The provided antibodies can mediate proliferation and activation of Treg cells, and can be used to treat autoimmune diseases, asthma, anaphylaxis, graft versus host disease, graft rejection, and a variety of other immune diseases.

This disclosure provides small molecule pyrrole-3-carboxamide compounds, compositions thereof, and methods of using them to modulate DCAF1 and treat a variety of diseases, disorders or conditions associated with DCAF1, such as neurological disorders like Alzheimer's disease, Parkinson's disease or Huntington's disease, transplant rejection, AIDS-related Kaposi's sarcoma, and particularly cancer.

New methods for assessing the status of transplant rejection in transplant recipients, such as kidney transplant recipients, are disclosed. The diagnostic methods utilize the measurement of TCR subunit repertoire diversity to identify stable subjects, subjects undergoing cell-mediated rejection processes, and subjects undergoing antibody-mediated rejection processes. The proportion of unique TCR alpha and beta subunit sequences to the total unique TCR subunit sequences (total sequences of alpha, beta, delta, and gamma subunits) provides a diagnostic measure that can identify stable subjects, subjects undergoing cell-mediated rejection processes, and subjects undergoing antibody-mediated rejection processes. If antibody-mediated rejection or cell-mediated rejection is detected, treatment methods include administration of appropriate therapy.

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).

In various aspects and embodiments, the disclosure provides cell populations, or "banks" of cells thereof (e.g., cell collections), to provide immunocompatible, allogeneic cell therapies covering global, ethnical, and disease-specific populations. In various aspects and embodiments, the cell banks and progeny thereof maintain sufficient HLA class I and HLA class II functions while promoting patient mating to prevent or reduce graft versus host disease (GVHD) or graft rejection. The disclosure further provides methods for creating a cell bank by gene editing, and methods for cell therapies involving cells or tissues derived from a cell bank, including but not limited to hematopoietic stem cells or "HSCs", progenitor cells, or progeny thereof.

Disclosed is the use of a JAK inhibitor [1,2,4]-triazolo-[1,5-a]0pyridine compound in the preparation of drugs for treating autoimmune, inflammatory or allergic diseases, or diseases such as transplant rejection. The JAK inhibitor [1,2,4]-triazolo-[1,5-a]-pyridine compound comprises a compound as shown in formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof. The JAK inhibitor has a good efficacy in animal model tests of diseases such as autoimmune, inflammatory or allergic diseases.

In the various aspects and embodiments, the present disclosure provides cell populations or cell “banks” thereof (e.g., cell collections) to provide immune compatible, allogeneic cell therapies covering global, ethnic, and disease-specific populations. In the various aspects and embodiments, the cell banks 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 cell banks by gene editing, and methods for cell therapy involving cells or tissues derived from the cell banks (including but not limited to hematopoietic stem cells, or “HSCs”, progenitors, or progenies thereof).

The present disclosure relates to compositions and methods for detecting rejection status of a transplant in a subject comprising detecting a B cell expression pattern in the subject and comparing the detected expression pattern to a control expression pattern, wherein a statistically significant difference in the two patterns indicates the transplant rejection. Also disclosed herein, is a method for treating a transplant rejection and a kit for detection of a transplant rejection status in a subject.

The present application provides a kind of CD47 mutant and its application, wherein CD47 mutant includes the amino acid sequence of partial amino acid sequence of CD47 and glycosyl phosphatidyl inositol (GPI) connection signal.The CD47 mutant is obtained by removing potential cell survival inhibition, blood flow and angiogenesis inhibition and other negative effect signal transduction sequences (transmembrane region and intracellular region) in CD47, while the beneficial functional segment (extracellular IgV domain) involved in inhibiting the phagocytosis of myeloid cells and its cytotoxic activity in CD47 sequence is fused with GPI membrane anchor connection signal sequence from human decay accelerating factor (DAF) protein.The obtained CD47 mutant can protect cells and organ transplants from being mediated by myeloid cells and other SIRP alpha positive immune cells with equal efficacy to wild type CD47, and at the same time eliminates the negative effects of wild type CD47.

This document provides methods and materials involved in reducing cardiac xenograft rejection. For example, methods and materials for preparing transgenic pigs expressing reduced or no endogenous Sda or SDa-like glycans derived from the porcine β1,4 N-acetyl-galactosaminyl transferase 2 (B4GALNT2) glycosyltransferase and / or reduced or no endogenous α-Gal antigens, methods and materials for modifying the xenograft recipient's immunological response to non-Gal antigens (e.g. CD46, CD59, CD9, PROCR, and ANXA2) to reduce cardiac xenograft rejection, and methods and materials for monitoring the progress of xenotransplant immunologic rejection are provided.

Disclosed herein are computer-implemented systems, kits, and methods for outputting an amount of contributor-derived nucleic acids in a biological sample, from a pregnant transplant recipient, that comprises nucleic acids from at least three genetically distinct contributors. The amount of contributor-derived nucleic acids may be useful in monitoring the status of a transplant for, e.g., assessing a risk of transplant rejection. In some examples, the at least three genetically distinct contributors may comprise a maternal genomic contributor, a fetal genomic contributor, and a transplant donor genomic contributor. For example, the systems and methods determine an estimated percentage of the contributor-derived nucleic acids and / or estimated percentage of the fetal-derived nucleic acids.

Provided herein are compositions comprising microgels conjugated to a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide, a Fas ligand (FasL) polypeptide, or both. Methods of making the microgel compositions as well as pharmaceutical compositions comprising thereof are also contemplated herein. Provided herein are also methods of inducing an immune privileged environment for transplantation, methods of treating or preventing graft rejection in a subject in need thereof, as well as methods of treating Type 1 diabetes.

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 dry eye disease, 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), cancer, myelofibrosis, and asthma. Also included are compositions comprising the double stranded oligonucleotide and methods of treatment using the double stranded oligonucleotide.

The present invention relates to double stranded oligonucleotides that are complementary to JAK1, which elicit modulation of the expression of JAK1. Modulation of JAK1 expression is advantageous for a range of medical conditions 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. The invention also includes compositions comprising the double-stranded oligonucleotides and methods of treatment using the double-stranded oligonucleotides.