42 results about "Graft rejections" patented technology

Methods of using IL-2 fusion proteins to treat and / or prevent graft rejection, such as cardiac graft rejection, are disclosed.

Provided herein are methods and compositions for treating kidney-related diseases disorders, and complications, such as Berger's disease and for preventing transplant rejections. For example, the present disclosure describes methods of improving transplanted kidney function 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.

Compositions of matter and means useful for treatment of autoimmunity and / or transplant rejection through generation of T regulatory cells in a manner that recapitulates thymic development. Methods of seeding thymic medullary epithelial cells with pluripotent stem cells such as inducible pluripotent stem cells, followed by exposure to conditions allowing for selective growth and expansion of T regulatory cells. T regulatory cells can be scaled for clinical utilization through the use of three-dimensional adhesive growth matrices as well as addition of FoxP3 inducing cytokines such as interleukin-2.

The present invention concerns the use of a molecule chosen from a globin, a globin protomer or an extracellular hemoglobin of Annelids, for treating and / or preventing at least one complement-activation associated disease, preferably ischemia / reperfusion injury and / or transplant rejection.

The present invention provides: a novel azabicyclo derivative compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing or treating autotaxin-related diseases, comprising the same as an active ingredient. The azabicyclo derivative compound according to the present invention exhibits excellent inhibitory activity against autotaxin, and thus can be used for treating and preventing diseases associated with autotaxin inhibition. The compounds can be used for treating diseases such as fibrotic diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, metabolic diseases, cancers and cancer metastases, ocular diseases, cholestatic and other forms of chronic pruritus, and acute or chronic organ transplant rejection.

This disclosure relates to anti-human CD154 antibodies with modified effector function. This disclosure also relates to the use of these anti-human CD154 antibodies in treating conditions associated with CD154 activation, such as transplant rejection, inflammatory conditions and disease, dysfunctional immune responses associated with viral infections and diseases, autoimmune conditions and disease, allergic conditions, atherosclerotic conditions, or neurodegenerative conditions and diseases. It also relates to the use of these anti-human CD154 antibodies in inducing central tolerance and hematopoietic chimerism in transplant patients.

The present disclosure relates to a pharmaceutical composition comprising an exosome derived from a thrombin-treated stem cell as an effective ingredient for preventing or treating a skin wound, a pharmaceutical formulation containing the same, and a production method thereof. Being a cell-free agent, an exosome-based therapeutic agent of the present disclosure has a low risk of carcinogenesis and no problems of graft rejection as well as being little liable to occur microvascular obstruction. The agent, which is not a cell, but a material isolated from a cell, can be subjected to medication development into an off-the-shelf product which allows for the reduction of production cost. The agent has the advantage of exhibiting outstanding angiogenesis and skin wound treatment effects even at a low concentration of exosomes thanks to the thrombin treatment effect.

This disclosure relates to anti-human CD154 antibodies with modified effector function. This disclosure also relates to the use of these anti-human CD154 antibodies in treating conditions associated with CD154 activation, such as transplant rejection, inflammatory conditions and disease, dysfunctional immune responses associated with viral infections and diseases, autoimmune conditions and disease, allergic conditions, atherosclerotic conditions, or neurodegenerative conditions and diseases. It also relates to the use of these anti-human CD154 antibodies in inducing central tolerance and hematopoietic chimerism in transplant patients.

The present invention relates to interleukin-2 variants, to pharmaceutical compositions comprising said interleukin-2 variants, in a pharmaceutically acceptable carrier, and to their implementation in the prevention or treatment of cancer, or in the prevention or treatment of a disease selected from the group consisting of acute or chronic inflammatory diseases, allergic diseases, autoimmune diseases, graft-versus-host disease and graft rejection.

The invention relates to Interleukin-2 (IL-2) variants for the prevention or treatment of immune disorders, including with no limitations allergic, autoimmune, chronic or acute inflammatory and infectious diseases; graft-versus-host disease; graft rejection and cancer. The invention also relates to the use of said IL-2 variants for the screening of anti-IL-2 antibodies with pro-T-effector or pro-T-regulatory cell activity.

Described herein are methods, compositions, and systems useful for detecting transplant rejection and associated abnormal conditions in solid organ transplant recipients, such as pancreatic transplant recipients, pancreatic and kidney transplant recipients, and simultaneous pancreatic and kidney transplant recipients. Methods described herein may involve combined assessment of blood gene expression profiles from an assessment of particular, related mRNA transcript levels and donor-derived cell-free nucleic acids (dd-cfDNA) or each an independent assessment of the mRNA transcript level as well as an independent assessment of the dd-cfDNA. Genes that correlate with pancreatic transplant rejection in simultaneous pancreatic and kidney transplant recipients are also disclosed.

This invention discloses the role of the POFUT1 gene in determining the function of tissue-infiltrating CD4+ T cells and the application of related biomarkers in diseases, belonging to the field of biomedical technology. This invention discovers that POFUT1 is a decisive gene regulating the development of CXCR5+CD4 T cells; simultaneously, CXCR5+ and SLAMF1+CD4 T cells, as tissue-infiltrating source cells, possess the function of carrying out CD4 T cell-mediated antigen-specific killing and tissue destruction, leading to the pathogenesis of autoimmune diseases. Related applications include: using the POFUT1 gene, CXCR5+, and SLAMF1+CD4 T cells as biomarkers for the clinical diagnosis and treatment of diseases caused by tissue-infiltrating CD4 T cells, such as autoimmune diseases and xenotransplant rejection. The killing function of CXCR5+ and SLAMF1+CD4 T cells as tissue-infiltrating source cells can also be used to treat tumors.

The present invention provides, among other things, a method of prophylaxis for kidney rejection comprising administering to the recipient an alpha-biased IL-2 variant in conjunction with the kidney transplant. In another aspect, the present invention provides, among other things, a method of improving a kidney transplant in a recipient, comprising administering to the recipient an alpha-biased IL-2 variant in conjunction with the kidney transplantation at a therapeutically effective amount, wherein the improvement in the kidney transplant results in prolonged stability of the kidney transplant, survival of the recipient, and / or reduced rejection symptoms as compared to a control.

Described herein are kits, compositions, and methods for detecting porcine antigens in a biological sample. The kit comprises a support, an anti-porcine antibody coupled to the support, and instructions for preparing a lysate from a porcine donor source and contacting the lysate with the anti-porcine antibody. The kit can be used to determine the risk of graft rejection in a human subject accepting or considering graft from a porcine donor.

A computer-implemented method and system for predicting graft rejection are disclosed herein. The method and system can calculate, based on a score, whether graft rejection will occur in a transplant recipient or the probability of prediction of the degree to which graft rejection will occur. The score can be calculated based on transplant recipient data and one or more parameter weights. The transplant recipient data can include cell-free DNA from the transplant donor (dd-cfDNA) and one or more other types of parameters, such as one or more clinical parameters, one or more functional parameters, one or more immunological parameters, one or more transplant recipient characteristics, or one or more transplant characteristics. In some embodiments, the parameters used to calculate the probability of prediction do not include histological parameters.

The invention provides novel imidazoquinoline amine derivatives, having agonistic activities to Toll-like receptors (TLRs), in particular TLR7 and / or TLR8, pharmaceutical compositions thereof, and methods of treatment, reduction or prevention of 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 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 application provides an anti-CD3 monoclonal antibody, a bispecific antibody and application thereof, and particularly provides an antibody or antigen binding fragment, which comprises CDRs selected from at least one of the following: heavy chain variable region CDRs of SEQ ID NO: 1-3 or a conservatively modified form thereof; light chain variable region CDRs of SEQ ID NO: 4-6 or a conservatively modified form thereof. The antibody or antigen binding fragment has different affinities to CD3 proteins in different pHs, has weak binding capacity in normal pH animal tissues or peripheral blood, has low peripheral drug concentration, reduces the risk of off-target toxicity, has strong affinity to CD3 in tumor tissues or the periphery thereof, is beneficial to the distribution of the antibody to the tumor local part, increases the local drug concentration, and the bispecific antibody prepared from the antibody can promote the combination of T cells and tumor cells, has high safety and specificity, and can effectively treat tumors, autoimmune diseases, inflammatory diseases and / or transplant rejection.

The absence of regulatory T cells (Treg) may underlie disorders including but not limited to autoimmunity, dermatitis, periodontitis and even transplant rejection. Enhancing local numbers of Treg through in situ Treg expansion or induction is contemplated herein as a treatment option for these disorders. Current methods for in vivo Treg expansion are not Treg specific and are associated with many adverse side-effects. The data presented herein provides in vitro testing of a Treg-inducing microparticle providing a predictable controlled release for combinations of cytokines and drugs (e.g., IL-2, TGF-β, and / or rapamycin) resulting in targeted Treg migration. These controlled release microparticles are also capable of inducing FoxP3+ Treg in human cells in vitro suggesting that these compositions be developed into an in vivo Treg induction and expansion therapy.

The disclosure provides a method for treating and / or preventing graft rejection with A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member-13 (ADAMT S13). The disclosure provides a method for increasing ADAMTS13-mediated von Willebrand factor (VWF) cleavage in a subject that received a graft by administering ADAMTS13. The disclosure also provides a method of determining the likelihood that a subject will rejection a graft.

To provide IL-2 variants for improving interleukin-2 (IL-2)-based immunotherapies to prevent or treat immune disorders.SOLUTION: The invention relates to IL-2 variants for the prevention or treatment of immune disorders, without limitation, allergic, autoimmune, chronic or acute inflammatory and infectious diseases; graft-versus-host disease; graft rejection and cancer. The invention also relates to use of the IL-2 variants for screening anti-IL-2 antibodies having pro-T-effector or pro-T-regulatory cell activity.SELECTED DRAWING: None

The present disclosure relates to methods of treating or reducing the risk of transplant rejection or increasing a duration of time before transplant rejection occurs in a subject in need thereof (e.g., a human) by administering an antagonist that targets CD40 or CD154, such as an anti-CD40 antibody or an antigen-binding fragment thereof (e.g., a humanized anti-CD40 antibody or antigen-binding fragment thereof. The transplant may be an allogeneic or xenogeneic transplant (e.g., a cell, tissue, or organ or portion thereof).

The present disclosure relates to methods of treating or reducing the risk of transplant rejection, or extending the period before transplant rejection occurs, in a subject (e.g., a human) in need thereof by administering an antagonist that targets CD40 or CD154, such as an anti-CD40 antibody or antigen-binding fragment thereof (e.g., a humanized anti-CD40 antibody or antigen-binding fragment thereof). The transplant may be an allograft or a xenograft (e.g., cells, tissues, or organs, or portions thereof).

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.

To provide antibody compositions with improved stability exhibiting reduced fragmentation of antibody polypeptide chains during production and following storage.SOLUTION: The present disclosure is related to improved compositions and methods for treating T-cell-mediated diseases and disorders (e.g., autoimmune disorders, graft-versus-host-disease, and graft rejection). Provided are anti-αβTCR binding polypeptides, including antibodies, which comprise at least one amino acid substitution or modification that increases the stability of the binding polypeptide by reducing fragmentation of the light chain variable region. The methods provided herein generally involve administering to a subject in need thereof an effective amount of a stabilized, humanized binding polypeptide that is specific to the alpha beta T-cell receptor (αβTCR).SELECTED DRAWING: None

Disclosed are PD-L1 presenting compositions. The compositions may be used to effect immunomodulation in a variety of contexts. The compositions may be used to decrease rates of transplant rejection, including pancreatic islet cell transplantation. The compositions are useful for the treatment of type 1 diabetes.

The invention provides an anti-CD3 monoclonal antibody, a bispecific antibody and application of the anti-CD3 monoclonal antibody and the bispecific antibody, and particularly provides an antibody or an antigen binding fragment which comprises at least one of the following CDRs: a heavy chain variable region CDR in SEQ ID NO: 1-3 or a conservatively modified form thereof; sEQ ID NO: 4-6 or a light chain variable region CDR in a conservative modification form thereof. The antibody or the antigen binding fragment has different affinity with CD3 protein at different pH values, has weak binding capacity in animal tissues or peripheral blood with normal pH values, has low peripheral drug concentration, reduces off-target toxicity risk, has strong affinity with CD3 at tumor tissues or around the tumor tissues, is beneficial to distribution to local tumor, increases local drug concentration, and reduces the risk of off-target toxicity of the antibody or the antigen binding fragment in the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues or around the tumor tissues. The double antibodies prepared from the polypeptide can promote the combination of T cells and tumor cells, are high in safety and specificity, and can effectively treat tumors, autoimmune diseases, inflammatory diseases and / or transplant rejection.

A SERPINA3 protein variant or a coding sequence thereof, the use of a SERPINA3 protein, the SERPINA3 protein variant or the coding sequence thereof in the preparation of a drug for resisting inflammation, treating autoimmune diseases, and resisting transplantation rejection, and the use of the SERPINA3 protein variant in the preparation of an anti-tumor antibody.

The invention discloses an oxazolopyridine compound as well as a preparation method and medical application thereof. The structure of the compound is shown as a formula (I), the oxazolopyridine compound or the pharmaceutically acceptable salt, tautomer, meracemate, raceme, stereoisomer, metabolite, metabolic precursor, prodrug or solvate of the oxazolopyridine compound can be applied to the preparation of PD-L1 inhibitors, such as PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors, PD-L1 inhibitors and PD-L1 inhibitors. The compound is applied to preparation of immunomodulator drugs for preventing or treating tumors, autoimmune diseases, organ transplant rejection, infectious diseases and inflammatory diseases.

The present invention provides an in vitro method for obtaining and purifying regulatory T cells from thymic tissue (or thyTreg cells), which makes it possible to obtain more than 10 billion cells from a single thymus. These thyTregs obtained in the invention have a purity of more than 95% and very high suppressive capacity, survival and viability, in addition to being safe from a clinical viewpoint. The foregoing would not require the use of massive ex vivo cell expansion protocols. The transfer of these thyTreg cells to patients enables immune tolerance induction. Thus, said cells may be used as cell therapy to induce immune tolerance in the treatment and / or prevention of transplant rejections and in autoimmune diseases.