436 results about "Immune tolerance" patented technology

The present invention is based on the seminal discovery that targeted immunomodulatory antobodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antobodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immuno-suppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-β)) and regulatory T cells and / or immunosuppressive myeloid dendritic cells (DCs). By conteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

The present invention utilizes carrier particles to present antigen peptides and proteins to the immune system in such a way as to induce antigen specific tolerance. The carrier particle is designed in order to trigger an immune tolerance effect. The invention is useful for treatment of immune related disorders such as autoimmune disease, transplant rejection and allergic reactions.

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immune suppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-β) and regulatory T cells and / or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

The present invention is a natural, cell-free tissue replacement that does not require difficult or extensive preparation made by washing tissue replacement in a solution including one or more sulfobetaines and an anionic surface-active detergent and washing the tissue replacement in serial solutions of the buffered salt to remove excess detergent. The natural, cell-free tissue replacement may be a nerve graft that supports axonal regeneration, guides the axons toward the distal nerve end and / or is immunologically tolerated. Other forms of the invention are a composition and kit prepared by the method of making a native, cell-free tissue replacement. The present invention may be modified for use in diagnostic, therapeutic, and prophylactic applications.

Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired. Fusions with targeting peptides direct the fusions to the target, for instance a tumor, where the erythrocyte-binding ligands reduce or entirely eliminate blood flow to the tumor by recruiting erythrocytes to the target.

Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired.

The invention discloses a combined preparation containing IL-10 and rapamycin, able to induce immunosuppression and antigen-specific immune tolerance, and the use thereof in the treatment of diseases involving an excessive, dysfunctional or uncontrolled immune responses mediated by T cells.

The present invention relates generally to the field of generating fusion proteins to be used in cancer therapy, and more specifically, to nucleotide sequences encoding the fusion proteins, wherein the chimeric fusion proteins comprises at least one targeting moiety and at least one immunomodulatory moiety that counteracts the immune tolerance of cancer cells.

PCT No. PCT / US94 / 05844 Sec. 371 Date Jun. 6, 1995 Sec. 102(e) Date Jun. 6, 1995 PCT Filed May 24, 1994 PCT Pub. No. WO94 / 27622 PCT Pub. Date Dec. 8, 1993This invention provides a method for developing immune tolerance in xenogeneic organ graft recipients, in which lympho-hematopoietic cells from an intended organ graft recipient are differentiated within a xenogeneic surrogate, such as a fetal animal. After birth of the surrogate, the matured lympho-hematopoietic cells containing antigen specific regulatory cells, including suppressor cells, veto cells, select B cells, anti-idiotype antibodies, and other related factors responsible for antigen specific tolerance in a surrogate animal are reintroduced into the intended organ graft recipient, in conjunction with an organ transplant or a tissue transplant from the xenograft surrogate. The invention also provides an organ graft repopulated with cells from the intended organ graft recipient produced in a surrogate animal.

A transformed T-cell for T-cell therapy, and a composition including the same for anticancer immunotherapy. More particularly, the transformed T-cell is characterized by the transfection of a gene for coding a chimera protein. The T-cell, to which the gene for coding the chimera protein is transected, may improve the therapeutic effects induced by immune tolerance of cancer cells, and furthermore maximize anti-cancer effects by activating signal transduction to induce the activation of T-cells. Also, the disclosure allows treatments that minimize side effects such as the development of autoimmune diseases due to systematic T-cell activation.

The invention relates to fusion protein used to prevent and cure I type and II type diabetes and its preparation method and application. It supplies the fusion protein which is formed by glucagon analogy peptide GLP-1, GLP-1 mutant and IgG-Fc, its analogy factor lizard salivary gland polypeptide extendin-4 and IgG-Fc, and the application of the above fusion protein and its DNA used in diabetes prevention and therapy. The fusion protein can increase not only GLP-1 effect, but also the affinity and immunological tolerance of ligand, which is excreted with the form of homogeneity dimmer to improve polypeptide drug effect, overcomes the defect of the GLP-1 for short half-life, and simplifies purification process.

The present invention proposes formative agent of protein complex, in which a polyphenol is useful component, and the agent is useful as gene complex, cell adhesion inhibitor or immune tolerogen. The polyphenol of forming the agent is selected from catechin group consisting of epigallocatechin-gallate, tannic acids, or proanto-dianisidine, a protein of the protein complex is selected from proteins consisting of animal proteins composed of polypeptide chain of peptide-combined amino acids, vegetative proteins, nucleus proteins, glycogen proteins, lipo-proteins and metal proteins, the gene complex comprises by compositing genes by polyphenol catechins in order to introduce genes to cells of animals or human bodies, a cell composed of the cell adhesion inhibitor is selected from cells consisting of an animal cell including a stem cell, skin cell, mucosa cell, hepatocyte, islet cell, neural cell, cartilage cell, endothelial cell, epidermal cell, osteocyte or muscle cell isolated from human or animal organism, or sperm, ovum or fertilized egg of domestic animals or fishes and a tissue or an organ for transplantation of the immune tolerogen is selected from the tissue or the organ consisting of skin, blood vessel, cornea, kidney, heart, liver, umbilical cord, bowels, nerve, lung, placenta or pancreas.

The invention provides non-immunostimulatory polynucleotide antigen conjugates and methods for treating unwanted immune reactions in individuals using the non-immunostimulatory polynucleotide antigen conjugates.

Methods and pharmaceutical compositions are disclosed, effective in breaking-down immunological tolerance the CXC chemokine interferon gamma-inducible protein 10 (IP-10), resulting in the generation of self specific immunity to IP-10, for the treatment of diseases, such as autoimmune diseases, in which IP-10 plays a pivotal role in disease onset and / or progression, e.g., in multiple sclerosis (MS).

Antigen specific immune tolerance is induced in a mammalian host by administration of a toleragen in combination with a regimen of immunosuppression. The methods optionally include a preceding conditioning period, where immunosuppressive agents are administered in the absence of the toleragen. After the tolerizing regimen, the host is withdrawn from the suppressive agents, but is able to maintain specific immune tolerance to the immunogenic epitopes present on the toleragen. Optimally, the toleragen will have high uptake properties that allow uptake in vivo at low concentrations in a wide variety of tolerizing cell types.

An immunological tolerance-inducing agent comprising a mucosa-binding molecule linked to a specific tolerogen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific antigen, including hapten, which causes an unwanted immune response in said individual comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

An agent comprising a mucosa-binding molecule linked to a specific microbial antigen is disclosed. Further, a method of inducing immnunological tolerance in an individual against a specific microbial antigen, including hapten, which causes an unwanted immune response in said individual, comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Methods and compositions are described for the treatment of type I insulin-dependent diabetes mellitus and other conditions using newly identified stem cells that are capable of differentiation into a variety of pancreatic islet cells, including insulin-producing beta cells, as well as hepatocytes. Nestin has been identified as a molecular marker for pancreatic stem cells, while cytokeratin-19 serves as a marker for a distinct class of islet ductal cells. Methods are described whereby nestin-positive stem cells can be isolated from pancreatic islets and cultured to obtain further stem cells or pseudo-islet like structures. Methods for ex vivo differentiation of the pancreatic stem cells are disclosed. Methods are described whereby pancreatic stem cells can be isolated, expanded, and transplanted into a patient in need thereof, either allogeneically, isogeneically or xenogenically, to provide replacement for lost or damaged insulin-secreting cells or other cells.

The invention provides human interleukin interleukin-2 (IL-2) / Fc fusion protein. The human IL-2 of the fusion protein comprises all sequences of a human IL-2 extracellular region; the Fc fragments comprise a hinge region, a CH2 region and a CH3 region; the human IL-2 / Fc sequences are fused directly or through a connection sequence; and the Fc fragments are human or animal IgG, IgM, IgD and IgA orsubtypes thereof. The ADCC and CDC effective factor action can be eliminated, and in addition, the human IL-2 / Fc fusion protein has the compatibility with a recombinant IL-2 receptor so that the half-life period is obviously prolonged and also has all the biological activity of the IL-2 receptor. The IL-2 / Fc obviously improves the humoral immune response stimulated by the hepatitis B vaccine and the immunity of the CD8+T cells targeted to the hepatitis B vaccine. Moreover, the balance immune (suppression) of the effective T cells and the regulatory t cells can be adjusted under the action of the cyclosporine A so that the pancreatic islet transplantation immune tolerance is induced.

The present invention provides liposomal compositions for inducing immune tolerance. The compounds typically comprise a liposome displaying a specific antigen and also a binding moiety for a sialic acid binding Ig-like lectin (Siglec) expressed on B cells. The invention also provides methods for inducing tolerance to a protein or polypeptide antigen (e.g., a protein antigen) in a subject. The methods involve administering to the subject a pharmaceutical composition that co-presents both the antigen and a glycan ligand for a Siglec expressed on B lymphocytes.

The invention discloses an ELISA detection kit of food allergen specificity IgG4 antibody and preparation method thereof, using enzyme target rod coated by purified food allergen protein. The kit comprises: enzyme target rod coated by food allergen protein, human IgG2 titer, enzymic-lableled antibody, TMB substrate developing liquid, sample diluent, concentrated cleaning solution and termination reaction liquid. The specificity IgG4 antibodies in sample serum are bonded with the corresponding antigens fixed on the micropore surface of the enzyme target rod and the enzymic-lableled antibodies identify and bond with the IgG4 to form antigen-IgG4-antibody-enzyme composite. The absorbency is measured by the development reaction between the enzyme and substrate and the specificity IgG4 antibody concentration in sample serum is measured by standard curve. The allergen specificity IgG4 antibody concentration in sample serum is used as biology index of exposure state of food allergen and for judging the patient immune deviation and immune tolerance and monitoring the immunotherapy effectiveness of special food selected by patients.

The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and / or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

This invention relates to cellular-based therapies for increasing the level of regulatory T cells (Treg) and / or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. To provide these therapeutic effects, two allogeneic leukocyte populations are contacted (in vivo, in vitro or ex vivo) and one of these leukocyte population is modified to bear on its surface a low-immunogenic biocompatible polymer so as to prevent pro-inflammatory allo-recognition. Cellular-based preparations and processes for achieving cellular therapy are also provided.

Provided are viral display vehicles which display multiple sclerosis associated antigens on the surface thereof for induction of immune tolerance to autoantigens such as MOG. Also provided are methods and pharmaceutical compositions for treating multiple sclerosis using the viral display vehicles of the present invention.

The present invention relates generally to the field of generating fusion proteins to be used in cancer therapy, and more specifically, to nucleotide sequences encoding the fusion proteins, wherein the chimeric fusion proteins comprises at least one targeting moiety and at least one immunomodulatory moiety that counteracts the immune tolerance of cancer cells.

Methods and compositions for using N-hydroxysuccinimide and N-hydroxysulfosuccinimide to covalently couple protein(s) to the surface of red blood cells universally, rapidly and conveniently are provided. In one embodiment, the compositions promote immune tolerance in a subject. One embodiment provides autologous or allogenic red blood cells having whole protein(s) of interests conjugated to proteins on or within the plasma membrane of the red blood cells, wherein the conjugated proteins display at least one antigen to which immune tolerance is desired. The proteins are conjugated to the RBCs using carbodiimide chemistry. In a preferred embodiment, the whole proteins are conjugated using EDC in combination with NHS or sulfo-NHS.

The present invention provides an isolated population of adult hematopoietic stem cells (HSC) derived from embryonic stem cells (ESC) induced to differentiate in vitro by culturing ESCs in a medium with stem cell factor, interleukin (IL)-3, and IL-6. HSC of immunophenotype c-kit+ or c-kit+ / CD45+ from this population are isolated and injected either intra bone marrow or intravenously into myeloablated recipient individuals. This method allows for the establishment of banks of allogeneic ESC-derived adult stem cells for treatments of autoimmune diseases, immune deficiencies and induction of immunotolerance during organ transplantation. These allogeneic ESC-derived adult hematopoietic stem cells (HSC) may be used in reconstituting bone marrow, without the development of teratomas or graft versus host disease, despite crossing histocompatibility barriers. Additionally, allogeneic ESC-derived HSC can be used to prevent the development of autoimmune diseases or organ rejection during transplantation.

A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:33, to form a duplex structure between said compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in said cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.