197 results about "MHC class I" patented technology

There is provided a method for selecting a tolerogenic peptide by selecting a peptide which is capable of binding to an MHC class I or II molecule without further processing. There is also provided a peptide selected by such a method and its use in a pharmaceutical composition and a method to treat and / or prevent a disease. The present invention also relates to a composition which comprises the following myelin basic protein (MBP) peptides: MBP 30-44; MBP 83-99; MBP 131-145; and MBP 140-154. The composition may be used to treat a disease, in particular multiple sclerosis and / or optical neuritis and the invention also relates to such uses and methods.

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 hsp7o, 50-1000 micrograms for hsp9o, and 10-600 micrograms for gp96. The invention also provides a method for measuring tumor rejection in viva 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 hsp7o-peptide complexes are also provided.

Embodiments relate to methods and compositions for eliciting, enhancing, and sustaining immune responses, preferably multivalent responses, preferably against MHC class I-restricted epitopes. The methods and compositions can be used for prophylactic or therapeutic purposes.

Provided are fusion polypeptides comprising an engineered antibody and a stress protein that bind to antigens with high affinity, are highly immunogenic, exhibit MHC class I priming and are able to be produced in non-mammalian cells, such as E. coli.

Improved molecular vaccines comprise nucleic acid vectors that encode a fusion polypeptide that includes polypeptide or peptide physically linked to an antigen. The linked polypeptide is one that (a) promotes processing of the expressed fusion polypeptide via the MHC class I pathway and / or (b) promotes development or activity of antigen presenting cells, primarily dendritic cells. These vaccines employ one of several types of nucleic acid vectors, each with its own relative advantages: naked DNA plasmids, self-replicating RNA replicons and suicidal DNA-based on viral RNA replicons. Administration of such a vaccine results in enhance immune responses, primarily those mediated by CD8+ cytotoxic T lymphocytes, directed against the immunizing antigen part of the fusion polypeptide. Such vaccines are useful against tumor antigens, viral antigens and antigens of other pathogenic microorganisms and can be used in the prevention or treatment of diseases that include cancer and infections.

The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

A disulfide trap, comprising an antigen peptide covalently attached to an MHC class I heavy chain molecule by a disulfide bond extending between two cysteines, is disclosed. In some configurations, a disulfide trap, such as a disulfide trap single chain trimer (dtSCT), can comprise a single contiguous polypeptide chain. Upon synthesis in a cell, a disulfide trap oxidizes properly in the ER, and can be recognized by T cells. In some configurations, a peptide moiety of a disulfide trap is not displaced by high-affinity competitor peptides, even if the peptide binds the heavy chain relatively weakly. In various configurations, a disulfide trap can be used for vaccination, to elicit CD8 T cells, and in multivalent MHC / peptide reagents for the enumeration and tracking of T cells. Also disclosed are nucleic acids comprising a sequence encoding a disulfide trap. Such nucleic acids, which can be DNA vectors, can be used as vaccines.

Two-domain MHC polypeptides useful for manipulation of antigen-specific T-cells are disclosed. These polypeptides include MHC class II-based molecules that comprise covalently linked β1 and α1 domains, and MHC class I-based molecules that comprise covalently linked α1 and α2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and / or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, and to treat conditions mediated by antigen-specific T-cells.

The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and / or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and / or 3) comprises toxin effectors which retain toxin functions.

The present invention provides a method of treating a cell proliferative disease such as cancer by providing to a subject in need thereof an immunogenic composition comprising plasmid and peptide(s) or analogues thereof. In embodiments of the present invention there is provided methods and compositions for inducing, entraining, and / or amplifying the immune response to MHC class-I restricted epitopes of carcinoma antigens to generate an effective anti-cancer immune response.

A new method to capture, purify and expand antigen-specific T lymphocytes has been developed using magnetic beads coated with recombinant MHC class I molecules. This method was optimized using homogenous populations of naive T cells purified from mice transgenic for the 2C T cell receptor (TCR). These T cells were captured on beads coated with MHC class I molecules and the relevant antigenic peptides. MHC and peptide specificity was confirmed by the usage of irrelevant MHC peptide combinations. An enrichment of 800 to 1600 fold was measured, using 2C T cells mixed with irrelevant T cells, starting from a 2C T cell frequency of 1 / 3000. The same approach was used to purify antigen-specific CD8+ T cells from total CD8+ T cells from naive mice. The recovered cells could be expanded and specifically kill target cells in vitro; they had a significant effect in vivo as well. We expect this procedure to be suitable to purify and expand in vitro tumor- and virus-specific killer T cells for use in cell therapy.

A recombinant polypeptide and nucleic acid constructs capable of expressing the recombinant polypeptide are provided. The recombinant polypeptide comprises a chimeric polypeptide including an antigenic peptide being capable of binding a human MHC class I, a functional human beta-2 microglobulin and a functional human MHC class I heavy chain.