Abstract: The present invention is directed to the examination of the pattern of immunodominant T cell epitopes in the E6 protein of Human Papilloma virus and its further characterization in terms of its amino acid sequence and Human Leukocyte Antigen restriction. These epitopes are identified based on their ability to induce specific T cell responses and therefore, are important as sources of antigens for immunotherapies to treat cervical and other cancers. The present invention contemplates identifying a number of similar epitopes restricted by a wide variety of Human Leukocyte Antigen types so that they can be used together to develop preventative or therapeutic vaccines, which can be used for the general human population. The present invention also contemplates using E6 peptides of Human Papilloma virus as a diagnosis method to predict the probability of developing persistent cervical neoplasia in an individual.

Abstract: Rational design of immunotherapeutics relies on clear knowledge of the immunodominant epitopes of antigens. Current methods for identifying kinetically stable peptide-MHC complexes are in many cases inadequate for a number of reasons. Disclosed herein is a reductionistic system incorporating known participants of MHC class II antigen processing in solution to generate peptide pools from antigens, including those for which no immunodominant epitope has yet been identified, that are highly enriched for proteolytic fragments containing their immunodominant epitopes. HLA-DM-mediated editing contributes significantly to immunodominance and is exploited in discovering immunodominant epitopes from novel or previously uncharacterized antigens, particularly antigens associated with pathogens, tumors or autoimmune diseases.

Abstract: The present disclosure provides isolated preproinsulin-derived peptides of 8 or 9 amino acids, comprising the amino acid sequence WGPDPAA (SEQ ID NO: 1), isolated Class I peptide-HLA complexes presenting said peptides and isolated molecules having binding affinity for said peptides and/or said peptide-HLA complexes. Such compositions are useful in the treatment of type 1 diabetes mellitus (T1DM). Such isolated molecules can include a T cell receptor (TCR) having specific binding affinity for a peptide-MHC complex wherein the MHC is an HLA Class I molecule and the peptide is a preproinsulin-derived peptide of 8 to 10 amino acids, comprising the amino acid sequence WGPDPAA (SEQ ID NO: 1).

Abstract: The invention relates to a vaccine which comprises at least one antigen and a peptide comprising a sequence R1—XZXZNXZX—R2, whereby N is a whole number between 3 and 7, preferably 5, X is a positively charged natural and/or non-natural amino acid residue, Z is an amino acid residue selected from the group consisting of L, V, I, F and/or W, and R1 and R2 are selected independently one from the other from the group consisting of —H, —NH2, —COCH3, —COH, a peptide with up to 20 amino acid residues or a peptide reactive group or a peptide linker with or without a peptide; X—R2 may also be an amide, ester or thioester of the C-terminal amino acid residue, as well as the use of said peptide for enhancing a patient's adaptive immune response to an antigen.

Abstract: Single chain trimer (SCT) molecules are disclosed, comprising an MHC antigen peptide sequence, a ?2-microglobulin sequence and a full-length MHC class I heavy chain sequence, joined by linker sequences. Further described are nucleic acids encoding single chain trimers. Methods for expansion of antigen-specific T cell populations using single chain trimer molecules are also disclosed. In some configurations, these methods comprise co-culturing, in a first stage, CD8+ T cells from a donor with antigen presenting cells comprising an MHC antigen peptide, and co-culturing, in a second stage, the CD8+ T cells with cells comprising an SCT which has an MHC antigen peptide sequence identical to the sequence of the antigen peptide in the first stage. The methods can provide 10,000-100,000 fold expansion of antigen-specific CD8+ T cells within about 28 days after establishing culture, and can yield over 1 billion antigen-specific CD8+ T cells expanded from an individual donor.

Abstract: Provided herein is an antibody- or antibody fragment-targeted cationic immunoliposome complex prepared by a method comprising the steps of (a) preparing an antibody or antibody fragment; (b) mixing the antibody or antibody fragment with a cationic liposome and to form a cationic immunoliposome wherein the antibody or antibody fragment is complexed with the cationic liposome, but is not chemically conjugated to the cationic liposome and wherein said antibody or antibody fragment does not comprise a lipid tag; and (c) mixing the cationic immunoliposome with a therapeutic or diagnostic agent to form the antibody- or antibody fragment-targeted cationic immunoliposome.

Abstract: A process for the production of an antigen specific antigen binding domain using a transformed host containing an expressible DNA sequence encoding the antigen specific antigen binding domain, wherein the antigen specific antigen binding domain is derived from a variable region of the immunoglobulin isotype NAR found in fish.

Abstract: This invention relates to the field of anticancer therapy, and to the identification of immunogenic peptides derived from the human telomerase reverse transcriptase (hTERT). The present invention relates to polynucleotides encoding hTERT epitopes restricted to MHC class I molecule, analogs thereof and polyepitopes containing such epitopes and/or analogs. Are also included in the present invention, vector and cell comprising such polynucleotides. The present invention also concerns composition comprising hTERT polypeptides, corresponding polynucleotides, vectors and cells, for use in the treatment and/or prevention of cancer.

Abstract: The document provides to methods and materials for generating T cells (e.g., antigen-specific CD4+ T cells). For example, methods and materials for using nested MHC class II epitopes as vaccines to generate activated CD4+ T cells in vivo or as reagents to generate activated CD4+ T cells ex vivo are provided.

Abstract: An antigen presenting composition comprising a plurality of 2-component MHC class I complexes and a carrier is described. A method for activating a group of antigen-specific CD8+ T cells comprising incubation of a group of naïve CD8+ T cells with the antigen presenting composition is also presented. A method for inducing the proliferation of a group of antigen-specific CD8+ T cells comprising incubation of a group of naïve CD8+ T cells with the antigen presenting composition is further described.

Abstract: The present invention relates to disulphide bond stabilized recombinant MHC class II molecules. In particular, the present invention provides a recombinant MHC class II molecule, which comprises: (i) all or part of the extracellular portion of an MHC class II ? chain; (ii) all or part of the extracellular portion of an MHC class II ? chain; wherein (i) and (ii) provide a functional peptide binding domain and wherein (i) and (ii) are linked by a disulphide bond between cysteine residues located in the ?2 domain of said ? chain and the ?2 domain of said ? chain, wherein said cysteine residues are not present in native MHC class II ?2 and ?2 domains. Methods of producing these molecules in prokaryotic systems and various uses of these molecules form further aspects.

Abstract: The present invention relates to the use of telomerase-derived peptides for the treatment of any cancer patients, particularly for the treatment of patients with renal or prostate cancer.

Abstract: Isolated polynucleotides are provided which encode antibody VH and VL polypeptides, and anti-CD100 antibodies and antigen-binding fragments thereof. In another aspect, the invention provides a vector comprising a polynucleotide of the invention. In another aspect, the invention provides a host cell comprising the vector of the invention. In another aspect, the invention provides a method of producing an antibody of the invention, e.g., for treating diseases associated with CD100, including certain autoimmune diseases, inflammatory diseases, and cancers.

Abstract: The invention provides a method for the creation of peptide antigens comprising epitopes with at least a first modification comprising a shortened or lengthened amino acid side chain. By extension or shortening of the side chain with CH3/CH2 groups, for example, made by computer assisted modeling of the tumor antigen (peptide) bound in the MHC-I-groove, immunogenicity can be improved with minimal modification of adjacent tertiary structure, thereby avoiding cross-reactivity. Provided by the invention are methods of creating such antigens, as well as methods for therapeutic or prophylactic treatment of various conditions comprising administration of the antigens.

Abstract: The invention provides isolated regulatory immune cells as well as cell cultures and conditioned media derived therefrom. Also provided are methods of repressing B cell autoantibody production and/or secretion and methods of treating autoimmune disorders using regulatory immune cells or precursors thereto such as hematopoietic stem cells (HSC). The invention also provides methods of repressing B cell autoantibody production and/or secretion and methods of treating autoimmune disorders by administration of HSC and Macrophage-Colony Stimulating Factor (M-CSF). Further provided are methods of diagnosing in a mammalian subject a defect in regulatory cell mediated repression of autoantibody secretion by B cells.

Abstract: This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their ?1-?2 platform domain, to the intended target cell specifically. The ?1-?2 domain is contiguous with a heterologous ?3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the ?3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified ?3 domain of a MIC protein.

Abstract: The present invention relates to peptides capable of inhibiting cellular and immune stress responses in a eukaryotic cell. The invention provides compositions and methods for the treatment of human degenerative diseases and inflammation, utilizing these peptides.

Abstract: The invention relates to a peptide derived from an antigen recognized by autoantibodies, which peptide is reactive with autoimmune antibodies from a patient suffering from rheumatoid arthritis. The peptide according to the invention possesses a modified arginine residue. The invention also relates to antibodies against the peptide and a method of detecting autoimmune antibodies.

Abstract: The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN(A/I/L/V)FL (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule.

Abstract: Heteroclitic analogs of Class I epitopes are prepared by providing conservative or semi-conservative amino acid substitutions at positions 3 and/or 5 and/or 7 of these epitopes. The analogs are useful in eliciting immune responses with respect to the corresponding wildtype epitopes.