86 results about "Allograft rejection" patented technology

An implantable system control unit (SCU) includes means for measuring tissue impedance or other condition to determine allograft health, in order to predict or detect allograft rejection. The SCU also includes at least two electrodes coupled to means for delivering electrical stimulation to a patient within whom the device is implanted, and may also include a reservoir for holding one or more drugs and a driver means for delivering the drug(s) to the patient. In certain embodiments, the system is capable of open- and closed-loop operation. In closed-loop operation, at least one SCU includes a sensor, and the sensed condition is used to adjust stimulation parameters. Alternatively, this sensory “SCU” sounds an alarm, communicates an alarm to an external device, and / or is responsive to queries regarding sensed information, such as tissue impedance.

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

The present invention relates to methods and pharmaceutical formulations for orally delivering an antigen to induce tolerance. The antigen is combined with derivatized amino acids or salts thereof. The induction of oral tolerance may be applied clinically for the prevention or treatment of auto-immune diseases and clinical allergic hypersensitivities, and for the prevention of allograft rejection.

The invention relates to therapeutic antisense oligonucleotides directed against genes coding for phosphodiesterase (PDEs) and the use of these in combination. These antisense oligonucleotides may be used as analytical tools and / or as therapeutic agents in the treatment of disease associated with reduced cellular cAMP in a patient, such as inflammatory diseases of the respiratory tract including, for example, asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, bronchitis, chronic bronchitis, silicosis, pulmonary fibrosis, lung allograft rejection, allergic rhinitis and chronic sinusitis as well as other conditions in which an increase in cyclic AMP or a decrease in PDE levels is beneficial.

The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes.

This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia / reperfusion (I / R) injury of various tissues (e.g., I / R injury of heart muscle associated with heart attack or cardiac surgery, I / R injury of brain tissue associated with stroke, I / R injury of liver tissue, skeletal muscles, etc.), septic shock, anaphylactic shock, neurodegenerative diseases (e.g., Alzheimer's and Parkinson's diseases), neuronal injury, atherosclerosis, diabetes, multiple sclerosis, autoimmune uveitis, pulmonary fibrosis, oobliterative bronchiolitis, bronchopulmonary dysplasia (BPD), amyotrophic lateral sclerosis (ALS), sepsis, inflammatory bowel disease, arthritis, allograft rejection, autoimmune myocarditis, myocardial inflammation, pulmonary granulomatous inflammation, influenza- or HSV-induced pneumonia, chronic cerebral vasospasm, allergic encephalomyelitis, central nervous system (CNS) inflammation, Heliobacterium pylori gastritis, necrotizing entrerocolitis, celliac disease, peritonitis, early prosthesis failure, inclusion body myositis, preeclamptic pregnancies, skin lesions with anaphylactoid purpura, nephrosclerosis, ileitis, leishmaniasis, cancer, and related disorders.

The present invention provides compositions and methods of inhibiting or inducing activation of T cells in a patient. The methods comprise administering a therapeutically effective dose of pharmaceutical compositions comprising a pharmaceutically acceptable carrier and peptides of between about 4 and about 20 residues, that bind antigen binding sites on MHC molecules encoded by substantially all alleles of a DR locus. These peptides are referred to as pan DR binding peptides. The pan DR binding peptides can be used to inhibit immune responses associated with immunopathologies, such as autoimmunity, allograft rejection and allergic responses. The peptides can also be used in combination with CTL peptides to enhance a CTL response.

An implantable system control unit (SCU) includes means for measuring tissue impedance or other condition to determine allograft health, in order to predict or detect allograft rejection. The SCU also includes at least two electrodes coupled to means for delivering electrical stimulation to a patient within whom the device is implanted, and may also include a reservoir for holding one or more drugs and a driver means for delivering the drug(s) to the patient. In certain embodiments, the system is capable of open- and closed-loop operation. In closed-loop operation, at least one SCU includes a sensor, and the sensed condition is used to adjust stimulation parameters. Alternatively, this sensory “SCU” sounds an alarm, communicates an alarm to an external device, and / or is responsive to queries regarding sensed information, such as tissue impedance.

A method of determining the acute allograft rejection status of a subject, the method comprising the steps of: determining the nucleic acid expression profile of one or more than one nucleic acid markers, or one or more than one proteomic markers in a biological sample from the subject; comparing the expression profile of the one or more than one nucleic acid markers to a control profile; and determining whether the expression level of the one or more than one nucleic acid markers is increased relative to the control profile, wherein the increase of the one or more than one nucleic acid markers is indicative of the acute rejection status of the subject.

Methods of treating autoimmune disorders, coronary artery disease, allergy symptoms, allograft rejection sepsis / toxic shock are disclosed. Some methods comprise administering one or more regulatory compositions to activate the T suppressor cells by increasing the acetylation level and / or protein level of FOXP3 in combination with a T suppressor stimulus and / or an antigen. Some methods comprise administering one or more regulatory compositions to activate the T suppressor cells by increasing the acetylation level and / or protein level of FOXP3. Some methods comprise administering soluble GITR or antibodies that bind to GITR ligand. Methods of treating cancer, infectious diseases, and immune deficiency are also disclosed as are vaccination methods. The methods comprise administering one or more regulatory compositions to inactivate the T suppressor cells by reducing the acetylation level and / or protein level of FOXP3. Improved vaccines and vaccination methods are disclosed. Methods of identifying compounds that are useful to modulate acetylation level and / or protein level of FOXP3 and treat diseases are disclosed.

The invention includes processes mainly for the treatment of a inflammatory diseases, such as inflammatory bowel disease, arthritis, atherosclerosis, asthma, allergy, inflammatory kidney disease, circulatory shock, multiple sclerosis, chronic obstructive pulmonary disease, skin inflammation, periodontal disease, psoriasis and T cell-mediated diseases of immunity, including allergic encephalomyelitis, allergic neuritis, transplant allograft rejection, graft versus host disease, myocarditis, thyroiditis, nephritis, systemic lupus erthematosus, and insulin-dependent diabetes mellitus. The processes involve treating a patient with a pharmaceutical composition containing an active ingredient that inhibits the activity of sphingosine kinase.

The present invention relates to derivatives and analogues of adenine of the formula: wherein L, A, Y and Z are those defined herein. Compounds of the present invention are useful in inhibiting adenylyl cyclase activity. The present invention also relates to a method of preventing and inhibiting a patient's fibroproliferative vasculopathy following vascular injury or a vascular surgical operation which includes administering to the patient, an effective amount of a compound according to the invention subsequent to a vascular injury, or subsequent to a vascular surgical operation, for one to two weeks after the injury or surgical operation, effective to treat or prevent a patient's fibroproliferative vasculopathy such as chronic allograft rejection or vascular restenosis following vascular trauma. The present invention also relates to a method for measuring the inhibition of adenylyl cyclase activity and a method for treating congestive heart failure.

Provided herein are compositions comprising anti-HLA-Ib antibodies as IVIg mimetics and methods for using the same for the prevention, treatment, therapy and / or amelioration of inflammation induced diseases and allograft rejection. In certain embodiments, the anti-HLA-Ib antibodies (monoclonal antibodies or mixed monoclonal antibodies, recombinant or chimeric or humanized or human antibodies) strongly mimic IVIg in immunoreactivity to HLA class Ia (HLA-A, HLA-B and HLA-Cw) and Ib antigens (HLA-E, HLA-F and HLA-G). In certain embodiments, the anti-HLA-Ib antibodies (monoclonal or mixed monoclonal antibodies; recombinant, chimeric, humanized or human antibodies) strongly mimic IVIg in immunomodulatory or immunosuppressive activities. While anti-HLA-Ib mAbs can be used to restore anti-tumor activities of CD8+ T cells and Natural killer cells by passive therapy in cancer patients, methods are also provided herein to induce production of polyclonal anti-HLA-Ib antibodies in cancer patients for restoring anti-tumor activities of CD8+ T cells and NK cells, by active specific immunotherapy.

Aptamer oligonucleotides specifically bind to the DNA binding site of proteins such as Sp1 and Sp1-related proteins which regulate the genes which encode costimulatory molecules such as CD28 and cytokines such as IL-2 and GMCSF. The oligonucleotides compete with the DNA-binding sites of regulatory proteins which specifically regulate molecules to modulate T-cell activation. This serves to modulate gene expression by preventing transcription of the gene. Aptamers are administered to provide therapies for diseases which involve aberrant T-cell activation such as psoriasis, Type I (insulin-dependent) diabetes mellitus, multiple sclerosis, autoimmune uveitis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease (Crohn's and ulcerative colitis), and septic shock and to regulate normal T-cell activation such as in allograft rejection.

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

The present invention relates to the use of immunogenic peptides comprising a T-cell epitope derived from an allograft antigen and a redox motif such as C-(X)2-[CST] or [CST]-(X)2-C in the prevention and / or treatment of allograft rejection and in the manufacture of medicaments therefore.

The present invention relates to the use of immunogenic peptides comprising a T-cell epitope derived from an allograft antigen and a redox motif such as C—(X)2-[CST] or [CST]-(X)2-C in the prevention and / or treatment of allograft rejection and in the manufacture of medicaments therefore.

The present invention relates to the use of collagen and MHC-like compounds to down regulate immune responses. Methods for administration of such compounds that induce immune tolerance are described. The invention is important in the context of allograft rejection, transplantation, graft rejection, pleural disease and immunotolerance.

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn s disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

The present invention relates to novel compounds of 2-propene-1-one series, of general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them, wherein R5, R6, Q and Y are as defined in the specification. The present invention also relates to a process for preparing such compounds, compositions containing such compounds, and use of such compound and composition in medicine. The compounds of the general formula (I) induce HSP-70 and are useful for the treatment of diseases accompanying pathological stress in a living mammalian organism, including a human being, such as stroke, myocardial infarction, inflammatory disorder, hepatotoxicity, sepsis, diseases of viral origin, allograft rejection, tumourous diseases, gastric mucosal damage, brain haemorrhage, endothelial dysfunctions, diabetic complications, neuro-degenerative diseases, post-traumatic neuronal damage, acute renal failure, glaucoma and aging related skin degeneration.

The present invention provides an isolated polypeptide capable of binding to aCAM-1, comprising the integrin (XL I domain or biologically active portion thereof, wherein one or more residues is substituted, wherein the substituted polypeptide binds ICAM-I at a higher affinity than wild type integrin CCL protein. The invention provides a method for inhibiting ICAM-I and a pharmaceutical composition comprising an integrin (XL I domain polypeptide or biologically active portion of the polypeptides. The invention also provides a method of treating or preventing an LFA-I mediated ICAM-1 associated disease such as inflammation, artherosclerosis, allograft rejection, diabetes, T-cell mediated sensitization reaction, psoriasis, HIV infection, or rheumatoid arthritis.

The invention relates to a preparation and an application of universal targeted CD19 antigen chimeric receptor T cells. Concretely, the invention relates to a method for preparing targeted CD19 antigen chimeric receptor T cells. The method comprises delivering a gene editing substance to the T cell to shear TRAC and B2M genes; and cloning the targeted CD19 CAR and B2M-HLA-E fusion gene into a repair template vector to simultaneously introduce targeted CD19 CAR and B2M-HLA-E fusion gene homologous recombination repair templates into T cells. The universal targeted CD19 antigen chimeric receptorT cell has the advantages of small allograft rejection reaction, high yield, high safety, immediate availability, wide application range and the like.

The present invention provides novel means and methods for treating unwanted side effects in transplantations, such as GVHD and allograft rejection. The invention provides immunotoxins comprising an antibody and a toxic substance, whereby cocktails of such conjugates are directed to different targets associated with one population of cells, wherein one target is chosen from CD3 or CD7. The preferred combination is a cocktail directed against both CD3 and CD7.

The present invention provides an isolated polypeptide capable of binding to aCAM-1, comprising the integrin (XL I domain or biologically active portion thereof, wherein one or more residues is substituted, wherein the substituted polypeptide binds ICAM-I at a higher affinity than wild type integrin CCL protein. The invention provides a method for inhibiting ICAM-I and a pharmaceutical composition comprising an integrin (XL I domain polypeptide or biologically active portion of the polypeptides. The invention also provides a method of treating or preventing an LFA-I mediated ICAM-1 associated disease such as inflammation, artherosclerosis, allograft rejection, diabetes, T-cell mediated sensitization reaction, psoriasis, HIV infection, or rheumatoid arthritis.

The present invention relates to 5-lipoxygenase inhibitors. Compounds disclosed herein can be useful in the treatment of bronchial asthma, chronic obstructive pulmonary disorder, arthritis, type I diabetes, multiple sclerosis, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, cancer, pruritis, urticaria, atopic dermatitis, allergic rhinitis, other inflammatory and autoimmune diseases. Processes for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds and their use as 5-lipoxygenase inhibitors are also provided.