19 results about "Allograft rejection" patented technology

The methods and uses described herein relate to the modulation of the immune system by modulation of Sema3F levels and / or activity, e.g. suppressing allograft rejection or inflammation by administering a Sema3F agonist or increasing an immune response by administering a Sema3F inhibitor.

The present disclosure provides compositions, systems, devices, and methods for the delivery of therapeutics. Particularly, the disclosure provides composition, systems, and devices of the delivery of Janus kinase (JAK) inhibitors and uses thereof, such as for inhibiting allograft rejection or treating autoimmune diseases.

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.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) or allograft rejection in subjects receiving donor cells. Also disclosed are methods enhancing regulatory T (Treg) cells for use in preventing GVHD. Also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the treated Treg cells. Also disclosed are enhanced Treg cells produced by the disclosed methods that have been engineered to express chimeric antigen receptor (CAR) polypeptide cells.

The present invention relates to a prognostic method for determining a probability of allograft rejection using an infrared spectroscopy-based method coupled with a machine learning model. The invention also refers to a method for determining a probability of efficiency of an allograft rejection rescue therapy.

Pre-existing alloreactive memory T cells are a major barrier to the induction of allograft tolerance in organ transplant recipients. The use of Eomesodermin (Eomes) expression in memory T cells to determine the risk of allograft rejection in a subject is described. Also described is the use of Eomes expression in memory T cells of transplant recipients to modify immunosuppressive therapy.

The invention features compositions and methods for treating transplant recipients (e.g., chronic allograft rejection) using a senolytic agent and an angiotensin II receptor antagonist or using a senolytic agent and senomorphic agent. The methods and compositions are useful in a variety of transplant settings including, without limitation, solid organ transplants including kidney, lung, heart, liver, intestine, or pancreas transplantation procedures and cellular transplants including but not limited to bone marrow transplants.

Aspects of the present disclosure relate to methods and compositions relating to the selection and expansion of immune cells, including T cells expressing CD16Hi in combination with a V [delta] 2 T cell receptor. The T cells generated by the methods disclosed herein are suitable for allogeneic cell therapy as they do not induce graft versus host disease (GvHD) and resist host immune allogeneic rejection. Thus, such cells are suitable for ready-to-use in clinical therapy for diseases such as cancer, infectious diseases, autoimmune diseases, heart diseases and neuronal diseases.

The present disclosure generally relates to methods of inhibiting an immune response and an immune response involved in transplant rejection, such as an allograft transplant rejection. In particular, the invention relates to the use of specific enzyme inhibitors that can be used to treat transplant rejection and / or prolong the survival of transplanted tissue or organs, in particular allotransplanted tissue or organs.

The disclosure provides uses of anti-CD40 ligand antibodies for immunosuppression in islet cell transplantation in subjects having type 1 diabetes (T1D). The disclosure also provides uses of compounds that block the interaction between CD40 and CD40 ligand, including such anti-CD40 ligand antibodies and antigen binding fragments thereof, for preventing or reducing islet cell allograft rejection in subjects having T1D, for restoring physiological insulin secretion or hypoglycemia awareness in a subject having T1D, or for treating subjects having T1D and / or treating subjects having T1D and partial graft function of islet cells where the subjects have had a previous allogenic islet cell transplant.

Compositions that include a cationic peptide hydrogel and an immunosuppressive small molecule drug are described. The small molecule drug is crystallized and dispersed in the peptide hydrogel to allow for slow release of the drug. Methods of inhibiting allograft rejection and treating autoimmune-mediated organ damage by local administration of the peptide hydrogel compositions are described.

Disclosed herein includes a method for treating antibody-mediated kidney allograft rejection, comprising treating a subject determined to suffer from antibody-mediated kidney allograft rejection more than 6 months after transplantation by administering an anti-CD38 antibody or antigen-binding fragment thereof (e.g., daratumumab, felzartamab, or isatuximab) to the subject; extracting cell-free DNA from a blood, plasma, serum or urine sample collected from the subject after conclusion of the treatment; quantifying an amount of donor-derived cell-free DNA, a percentage of donor-derived cell-free DNA out of total cell-free DNA, or both, in the extracted DNA; and retreating the subject with an anti-CD38 antibody or antigen-binding fragment thereof if the amount of donor-derived cell-free DNA, the percentage of donor-derived cell-free DNA out of total cell-free DNA, or both, exceed one or more threshold values.

Methods of reducing allograft rejection or the risk of allograft rejection in a subject are described. The methods include metabolically labelling an allograft tissue or organ with a chemical tag (such as dinitrophenyl), transplanting the labelled tissue or organ, and administering to the transplant recipient T regulatory (Treg) cells expressing a chimeric antigen receptor (CAR) specific for the chemical tag. The CAR-expressing Treg cells are stimulated upon binding to the chemical tag displayed on the transplanted tissue or organ, leading to activation of the Treg cells and suppression of effector CD8+ T cells, thereby generating of an immunosuppressive tissue environment that reduces the risk of allograft rejection. Kits that include a chemical tag, engineered CAR Treg cells specific for the chemical tag, and / or a viral vector encoding a CAR specific for the chemical tag are also described.

The methods and uses described herein relate to the modulation of the immune system by modulation of Sema3F levels and / or activity. e.g. suppressing allograft rejection or inflammation by administering a Sema3F agonist or increasing an immune response by administering a Sema3F inhibitor.

The invention discloses a nano self-assembly body capable of reducing allograft rejection. The nano self-assembly body is a nano particle obtained by self-assembling an artesunate-mycophenolic acid ester self-assembly body prodrug and DSPE-PEG2000, wherein the artesunate-mycophenolic acid ester self-assembly body prodrug and the DSPE-PEG2000 are of the following structure. The invention also discloses a preparation method and application of the nano self-assembly body. In addition, the invention also discloses a structure and a preparation method of the artesunate-mycophenolate self-assembly prodrug. In the preparation process of the nano self-assembly, artesunate and mycophenolic acid ester are synthesized into a prodrug through esterification reaction, and then the prodrug is combined with DSPE-PEG2000 to prepare the nano drug. The nano-drug has the characteristic of accurately targeting the spleen, and can effectively remodel the immune microenvironment after transplantation. Through research and development of the nano-drug, the problem of toxic and side effects caused by long-term use of a traditional immunosuppressor and the problem of poor treatment effect of a natural small-molecule immunosuppressor are successfully solved, and the nano-drug shows extremely wide development prospects and huge potential in the field of future clinical application.

Pre-existing alloreactive memory T cells are a major barrier to the induction of allograft tolerance in organ transplant recipients. The use of Eomesodermin (Eomes) expression in memory T cells to determine the risk of allograft rejection in a subject is described. Also described is the use of Eomes expression in memory T cells of transplant recipients to modify immunosuppressive therapy.

Provided is a method for reducing or eliminating allograft rejection by using a thymus vaccine. The method comprises the following steps: expressing major histocompatibility complex (MHC) from a donor and / or grafting a thymus epithelial cell from a donor in the thymus tissue of a recipient by means of the thymus vaccine. The thymus vaccine includes a thymic gene vaccine and / or a thymocyte vaccine. The thymic gene vaccine is used for expressing an MHC antigen from the donor in the thymus of the recipient, and comprises: (1) a gene expression vector; and (2) polynucleotides separately encoding MHC class I molecules and MHC class II molecules of the donor. The thymocyte vaccine is prepared by the following steps: sorting by using an anti-Epcam antibody to give thymus epithelial cells. By establishing a convenient donor source, the limitations of allograft caused by MHC mismatch are overcome, thus helping solve the clinical problem of limited donor sources.

Embodiments of the invention include compositions and methods related to engineered human mucosal-associated invariant T (eMAIT) cells for off-the-shelf use for clinical therapy for cancer, infectious, and autoimmune diseases. In some embodiments, the eMAIT cells are produced from healthy human donor peripheral blood, cord blood, or G-CSF mobilized peripheral blood. In particular embodiments, the eMAIT cells are produced from a pluripotent stem cell line and therefore can be of unlimited supply. In some embodiments, the eMAIT cells are engineered to express chimeric antigen receptors (CARs), or / and immune regulatory molecules, or / and allorejection resistance molecules. Embodiments of the invention also include compositions of matter comprising polynucleotides encoding mucosal-associated invariant T cell receptor alpha chain polypeptides and / or mucosal-associated invariant T cell receptor beta chain polypeptides.

The invention provides agonistic TNFR2 antibodies and antigen-binding fragments thereof and encompasses the use of these antibodies as therapeutics to promote the proliferation of regulatory T cells (T-reg) for the treatment of immunological diseases. Antibodies of the invention can be used to potentiate the T-reg-mediated deactivation of self- and allergen-reactive T- and B-lymphocytes, and can thus be used to treat a wide variety of indications, including autoimmune diseases, allergic reactions, asthma, graft-versus-host disease, and allograft rejection, among others.