242 results about "Peptide complex" patented technology

The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising cancer antigenic peptides and uses there of.

Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. Optionally, the methods further comprise administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens / immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic / immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96.

Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

The present invention relates to methods and compositions for enhancing immunological responses and for the prevention and treatment of infectious diseases or primary and metastatic neoplastic diseases based on the administration of macrophages and / or other antigen presenting cells (APC) sensitized with heat shock proteins non-covalently bound to peptide complexes and / or antigenic components. APC are incubated in the presence of hsp-peptide complexes and / or antigenic components in vitro. The sensitized cells are reinfused into the patient with or without treatment with cytokines including but not limited to interferon- alpha , interferon- alpha , interleukin-2, interleukin-4, interleukin-6 and tumor neurosis factor.

The present invention provides methods for generating mammalian T cell populations comprising antigen-specific CD4+CD25+ regulatory T cells from freshly isolated CD4+CD25− T cells. The method comprises selecting CD4+CD25− T cells from a sample obtained from a mammalian subject; determining the MHC Class II type of the subject; inducing the generation of antigen-specific regulatory T cells by contacting the isolated CD4+CD25− T cells in a culture vessel with an induction agent for a time period sufficient to generate antigen-specific CD4+CD25+ regulatory T cells; and selecting the CD4+CD25+ antigen-specific regulatory T cells by sorting the cells in the induction culture with a selection agent comprising at least one artificial multimeric MHC Class II / peptide complex that corresponds to the MHC Class II type of the subject.

The present invention provides a novel process for producing sterile suspensions of slightly soluble basic peptide complexes. The present invention further provides a novel process for producing sterile lyophilizates of slightly soluble basic peptide complexes. In addition, a novel process for producing sterile suspensions suitable for the parenteral administration of slightly soluble basic peptide complexes is provided. The invention moreover provides sterile suspensions and sterile lyophilizates of slightly soluble basic peptide complexes, and pharmaceutical formulations comprising them. The provided sterile suspensions, sterile lyophilizates and pharmaceutical formulations comprising them are particularly suitable for use in a parenteral dosage form as medicaments for the treatment and prophylaxis of diseases and pathological states in mammals, especially in humans.

The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising Mycobacterium tuberculosis antigenic peptides and uses there of.

The invention provides methods for inhibiting the formation of undesired intracellular polypeptide complexes or aggregates associated with neurological disorders using an intrabody.

The present invention provides methods for generating mammalian T cell populations comprising antigen-specific CD4+CD25+ regulatory T cells from freshly isolated CD4+CD25− T cells. The method comprises selecting CD4+CD25− T cells from a sample obtained from a mammalian subject; determining the MHC Class II type of the subject; inducing the generation of antigen-specific regulatory T cells by contacting the isolated CD4+CD25− T cells in a culture vessel with an induction agent for a time period sufficient to generate antigen-specific CD4+CD25+ regulatory T cells; and selecting the CD4+CD25+ antigen-specific regulatory T cells by sorting the cells in the induction culture with a selection agent comprising at least one artificial multimeric MHC Class II / peptide complex that corresponds to the MHC Class II type of the subject.

The present invention provides of using multimeric MHC class II / peptide complexes. In one aspect, methods provided for identifying MHC class II-restricted immune epitopes of a predetermined polypeptide antigen. Methods for identifying an immunostimulatory epitope for a predetermined polypeptide antigen are provided. In a related aspect, methods for screening a therapeutic polypeptide agent for an MHC class II epitope are provided. In other aspects, methods for modulating T cells and for determining or monitoring an MHC class II-restricted immune status of a patient are also provided.

Biopolymer beads and hydrogels are useful in the remodeling, repair and reconstruction of the heart, as well as in modification of electrical conduction in the heart. Various types of beads are useful, including beads comprising a core of alginate polymers which may or may not be bonded to peptides; beads comprising a core in which peptides are dispersed with alginate polymers, and a chitosan film ionically bonded to available alginate polymers at the surface of the core; beads comprising a core in which peptides and chitosan derivates are dispersed with alginate polymers and form alginate-peptide complexes to which the chitosan derivatives are bonded; and beads comprising a core of chitosan polymers which may or may not be bonded to peptides. The heart may also be treated with a hydrogel agent comprising alginate polymers and peptides covalently bonded to the alginate polymers.

A composition of matter which comprises a metallic complex of the formula MZ+LnI wherein M is a metal ion of nutritional or therapeutic value; Ln is one or more oligopeptides wherein at least one oligopeptide comprises at least one amino acid selected from the group consisting of nonprotein amino acids and synthetic amino acids; n=1-3, Z=1-6. The metal ion of the metallic complex is selected from the group consisting of chromium, zinc, manganese, magnesium, calcium, copper, iron, vanadium, cobalt, molybdenum, germanium, selenium, and indium. The invention further provides food or drink compositions or dietary supplements which comprise the metallic complex of the invention.

The present invention relates to a recombinant soluble T cell receptor. The T cell receptor (TCR) is refolded and comprises a recombinant TCR alpha or gamma chain extracellular domain having a first heterologous C-terminal dimerisation peptide; and a recombinant TCR beta or delta chain extracellular domain having a second C-terminal dimerisation peptide which is specifically heterodimerised with the first dimerisation peptide to form a heterodimerisation domain, which may be a coiled coil domain. The invention also provides nucleic acid sequences encoding the recombinant TCR and a method for producing the recombinant TCR. The TCR may be labelled with a detectable label so as to enable the detection of specific MHC-peptide complexes. Alternatively, it can be linked to a therapeutic agent such as a cytotoxic agent or an immunostimulating agent so as to deliver such an agent to the site of a specific MHC-peptide complex.

The present invention relates to methods for making compositions comprising heat shock proteins or alpha (2) macroglobulin ("alpha2M"), which compositions are immunogenic against a type of cancer or an agent of an infectious disease, and the compositions produced by the methods described herein. The invention further relates to methods for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. Specifically, the present invention provides a method of eliciting an immune response comprise administering to an individual a composition made by mixing an amount of a purified first complex comprising a first heat shock protein or alpha2M complexed to a peptide which displays antigenicity of an antigen of said type of cancer or antigenicity of an antigen of an agent of said infectious disease; and an equal or greater amount of a second heat shock protein or alpha2M that is not complexed in vitro to a peptide which displays antigenicity of an antigen of said type of cancer or antigenicity of an antigen of an agent of said infectious disease, respectively; and is not in the form of a complex, said complex having been isolated as a complex from cancerous tissue of said type of cancer or cells infected with said agent of infectious disease, respectively. Optionally, the methods further comprise administering antigen presenting cells sensitized with hsp-peptide or alpha2M-peptide complexes comprising peptides antigenic to cancer cells or to an agent of an infectious disease.

An artificial antigen presenting cell includes a liposome having at least one recombinant soluble MHC-peptide complex incorporated therein. The artificial antigen presenting cell may also include at least one additional signal molecule incorporated therein for manipulating the intensity and quality of the immune response. The recombinant soluble MHC molecule is obtained by a method utilizing PCR amplification of gDNA or cDNA, and a tag is attached thereto for anchoring the recombinant soluble MHC molecule to the liposome.

In one aspect, the invention provides methods for determining the biological activity of heat shock proteins or heat shock protein-peptide complexes based on the ATPase activity or the multimeric structure of the heat shock proteins or heal shock protein-peptide complexes, and methods for screening agents that modulate the biological activity of heat shock proteins or heat shock protein-peptide complexes. In another aspect, the invention provides complexes, compositions and methods for enhancing the immunogenicity of a heat shock protein or a complex comprising a heal shock protein and an antigenic molecule.

Nanoparticles to treat autoimmune diseases and HIV infection are provided. The nanoparticles comprise a biocompatible polymer and a complex, wherein the complex is a major histocompatibility complex (MHC) class I antigen E (HLA-E) linked to a peptide, and wherein the HLA-E-peptide complex is linked to the surface of the nanoparticle. The present invention also relates to methods for treating autoimmune diseases and HIV infection.

The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens / immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic / immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96. The invention also provides a method for measuring tumor rejection in vivo in an individual, preferably a human, comprising measuring the generation by the individual of MHC Class I-restricted CD8+ cytotoxic T lymphocytes specific to the tumor. Methods of purifying hsp70-peptide complexes are also provided.

Methods and compositions for treating sepsis using cell membrane-permeant peptide conjugate covalent compounds having target cell specificity are provided.

The present invention provides a method of improving or prolonging a subject's immune response to a vaccine composition comprising heat shock protein (HSP)-peptide complexes or alpha-2-macroglobulin (alpha2M)-peptide complexes (hereinafter "HSP / alpha2M vaccine composition"). The HSP-peptide complexes or alpha2M-peptide complexes of the vaccine composition comprise HSP(s) or alpha2M complexed to a component against which an immune response is desired to be induced. In particular the invention is directed to methods of improving or prolonging a subject's immune response comprising administering an HSP / alpha2M vaccine composition in conjunction with a preparation comprising HSP or alpha2M, alone or complexed to a peptide that is not the component against which an immune response is desired to be induced (hereinafter "HSP / alpha2M preparation"), i.e., the HSP / alpha2M preparation does not display the immunogenicity of the component. In particular, HSP / alpha2M vaccine compositions are administered in conjunction with HSP / alpha2M preparation to improve or prolong the immune response of a subject against an infectious disease or cancer.

The invention relates to a method for isolating from connective tissue a variety of glycosminoglycan (GAG)-polypeptide complexes and polypeptides which are substantially free of contaminating DNA and other molecules such as viruses which may be associated with the DNA in the cell. The invention also relates to uses of GAG-peptide complexes and polypeptides substantially free of DNA either directly, or after further processing, for the treatment, protection and restoration of connective tissues in inflammatory and degenerative disorders such as rheumatoid arthritis and osteoarthritis in any of their multiple forms or other degenerative conditions in mammals.

The invention relates to the method for producing antipeptide cytotoxic T lymphocytes (CTLs) by attaching a complex of a class I HLA and a peptide to antigen presenting cell(s) (APCs) present in a sample of peripheral blood lymphocytes (PBLs), optionally removing excess class I HLA / peptide complex, and incubating with proliferative cytokine. The invention further relates to a CTL obtainable by these methods and to a method of treating a subject by administering such a CTL to the subject.

Disclosed are protein ligands comprising an immunoglobulin heavy chain variable (VH) domain and an immunoglobulin light chain variable (VL) domain, wherein the proteins bind a complex comprising an MHC and a peptide, do not substantially bind the MHC in the absence of the bound peptide, and do not substantially bind the peptide in the absence of the MHC, and the peptide is a peptide fragment of gp100, MUC1, TAX, or hTERT. Also disclosed are methods of using and identifying such ligands.

The invention relates to, among others, a method for assessing a prognosis of a patient with a malignant disease and / or for predicting the response of a patient with a malignant disease to immunotherapy. For this purpose, a DNA methylation analysis is carried out on at least one immunoregulatory gene of cells of the malignant disease and / or T lymphocytes which interact with the cells of the malignant disease, said gene coding for an immune checkpoint selected from B7 proteins and the receptors thereof, MHC-peptide complex-binding co-receptors, the members of the tumor necrosis factor receptorsuperfamily TNFRSF9, CD40, TNFRSF4, TNFRSF18, and CD27, the members of the immunoglobulin superfamily TIGIT, BTLA, HAVCR2, BTNL2, and CD48, and the andenosine-binding adenosine 2A receptor.

Compositions and methods are provided for producing a complex between a double stranded (ds) nucleic acid and a peptide, comprising: a. solubilizing the nucleic acid in an aqueous solution; b. solubilizing the peptide in an aqueous solution; and c. mixing the solubilized ds nucleic acid and the solubilized peptide in the presence of an organic salt.

The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on an immune cell, conjugated via a linker to a second peptide ligand, which binds to a component present on a cancer cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.