Abstract: The present invention provides compositions, methods, and systems for generating antigen-specific long-term memory T-cells using mTOR pathway inhibitors. The present invention provides compositions, systems, and methods for administering antigen-specific long-term memory T-cells to a subject (e.g., to a subject with cancer in adoptive transfer type of procedures).

Abstract: The present invention relates to a method of identifying a substance altering glucose uptake and/or GLUT4 translocation to the plasma membrane of a cell comprising contacting a test system comprising AKT substrate 160 kDa-protein (AS160-protein) with a test substance, and identifying a test substance as a substance altering glucose uptake of a cell by detecting a signal indicative for altered glucose uptake of a cell; a test system comprising a gene coding for the AKT substrate 160 kDa-protein (AS160-protein) and an inducible promoter providing for controllable expression of the gene; the use of the test system for the identification of a substance improving glucose uptake and/or GLUT4 translocation to the plasma membrane of a cell; and the use of AS 160-protein in a model for type 2 diabetes.

Abstract: The invention relates to a method for the preparation of efficient antigen-presenting human ?? T cells, to the ?? T cells prepared by such a method, and to their use in immunotherapy, vaccination, vaccine development and diagnostics. Similar to dendritic cells (DCs) in potency and efficacy, these human ?? T cells process antigens and present antigenic peptides to ?? T cells and induce antigen-specific responses (proliferation and differentiation) in naïve ?? T cells. ?? T cells are easily purified from peripheral blood, acquire “maturation” status (expression of essential adhesion, co-stimulatory and major histocompatibility complex molecules) within 1 day of in vitro culture under stimulation and induce strong primary and secondary T helper cell and cytotoxic T cell responses. The ?? T cells may be used in a method of treatment of tumors or chronic or recurrent infectious diseases, in identification of novel tumor or pathogen-derived antigens, and in the diagnosis of the immune competence of a patient.

Abstract: The invention provides an isolated or purified nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12. The invention also provides a nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12, wherein the NFAT promoter is located 3? of the nucleotide sequence encoding IL-12. Also provided are related recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. The invention further provides the use of the inventive nucleic acids or related materials in the treatment or prevention of cancer or an infectious disease in a mammal and in the induction of IL-12 expression in a mammal.

Abstract: The invention relates to compounds that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Abstract: Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo.

Abstract: Based upon a strong correlation between regulator T cells (Treg cells) and suppressing or preventing a cytotoxic T cell response, provided are methods for the production of ex vivo activated and culture-expanded isolated CD4+CD25+ suppressor Treg cells for the prevention or suppression of immune reactions in a host, particularly in a human host, and including autoimmune responses. The resulting ex vivo culture-expanded Treg cells provide a sufficient amount of otherwise low numbers of such cells, having long term suppressor capability to permit therapeutic uses, including the preventing, suppressing, blocking or inhibiting the rejection of transplanted tissue in a human or other animal host, or protecting against graft vs host disease. Also provided are therapeutic and immunosuppressive methods utilizing the ex vivo culture-expanded Treg cells for human treatment, and high efficiency methods for research use.

Abstract: Provided herein are isolated genomic polynucleotide fragments from the from the p15 region of chromosome 11 encoding human and tumor suppressing subtransferable candidate 4 (TSSC4) and methods of use.

Abstract: The invention provides relatively short immunogenic peptides, and biologically active variants thereof, associated with leukemia which elicit an immune response. Nucleic acids encoding the immunogenic peptides and antibodies specific for the peptides are also provided. The immunogenic peptides can be included in pharmaceutical compositions, such as cancer vaccines, and used for the treatment of cancer.

Abstract: Methods of processing inactivated artificial antigen presenting cells (aAPCs) and artificial antigen presenting cells with specificity for selected antigenic peptides are described, including their generation and use in cell therapy compositions comprising activated cytotoxic T lymphocytes. Inactivated aAPCs are advantageously generated through crosslinking, such as via a photoreaction involving a psoralen derivative and UVA irradiation.

Abstract: The present invention to methods for producing mononuclear cells overexpressing IL-10. The method comprises the ex vivo introduction of an expression construct comprising a nucleotide sequence encoding a polypeptide having IL-10 activity into peripheral blood mononuclear cells of a subject. The thus obtained peripheral blood mononuclear cells have an altered phenotype as a result of the expression of an introduced IL-10 transgene. In particular the invention relates to CD4+ T cells that functionally behave as regulatory T cells as a result of the expression of an IL-10 transgene. The IL-10 transgenic mononuclear cells may be used to treat a variety of inflammatory diseases, particularly T helper 1-mediated inflammatory diseases.

Abstract: The present invention relates to cyclin D1-derived peptides for use in the improved treatment of cancer in a patient, particularly in the form of a combination therapy using a vaccine. Other aspects relate to the use of the peptides or a combination thereof as a diagnostic tool.

Abstract: The present invention relates to a peptide comprising or consisting of the following amino acid sequence: A0-A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12 (formula II), wherein A0 is a hydrophobic amino acid residue or is absent; A1, A4, A7, A8, A12 each are a hydrophobic amino acid residue; and A2, A6, A9, A10 each are a basic amino acid residue; A5 is an alanine or a basic amino acid residue; A3, A11 each are a basic amino acid residue, or a hydrophobic amino acid residue; or a peptidomimetic thereof; wherein the basic amino acid residues are selected from the group consisting of arginine, lysine and histidine; wherein the hydrophobic amino acid residues are selected from the group consisting of leucine, alanine, isoleucine, valine, methionine and phenylalanine; and wherein said peptide or peptidomimetic has antimicrobial and/or antiviral activity.

Abstract: Provided herein are isolated genomic polynucleotide fragments from the from the p15 region of chromosome 11 encoding human ribosomal protein L26 (RIBO26) and methods of use.

Abstract: The invention provides T cell receptors (TCRs) having antigenic specificity for a cancer antigen, e.g., tyrosinase. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a host and a method of treating or preventing cancer in a host using the inventive TCRs or related materials.

Abstract: The present invention relates to a method for generating an RNA library or a (poly)peptide library comprising the steps of: (a) providing one or more nucleic acid molecules each comprising i) two or more coding elements (A) each giving rise to an RNA molecule upon transcription and/or a (poly)peptide upon transcription and translation; and ii) linking elements (B) arranged according to the general formula of B(AB)2+n, wherein said linking elements comprise one or more sequence motifs not found in said two or more coding elements allowing specific disruption of the linking elements (B); (b) cloning the nucleic acid molecule of step (a) into a vector; (c) transforming a host cell with the vector obtained in step (b) and propagating said transformed cell; (d) preparing vector DNA from the transformed and propagated cells of step (c); (e) (i) disrupting the vector DNA obtained in step (d) with one or more agents recognizing said one or more sequence motifs of the linking elements or (ii) performing an amplificati

Abstract: Provided herein are isolated genomic polynucleotide fragments from the p15 arm of chromosome 11 encoding HASH2 and methods of use.

Abstract: Provided herein are isolated genomic polynucleotide fragments from the from the p15 region of chromosome 11 encoding human tumor suppressing subtransferable candidate 6 and methods of use.

Abstract: Provided herein are isolated genomic polynucleotide fragments from the from the p15 region of chromosome 11 encoding human SMS3 (SMS3) and methods of use.

Abstract: Compositions and methods for immunization against human breast cancer are disclosed. A breast cancer vaccine comprises an immunogenic polypeptide comprising human ?-lactalbumin.

Abstract: The present invention relates to a fusion protein comprising a protein transduction domain capable of introducing the fusion protein into a mammalian cell and an anti-apoptotic protein comprising the amino acid of the sequence of SEQ ID NO:1 or an anti-apoptotically active variant or fragment thereof. The invention also relates to a pharmaceutical composition comprising such a fusion protein, in particular for blocking apoptosis in a patient in need thereof. The invention also provides a polynucleotide encoding such a fusion protein, an expression vector comprising the polynucleotide and a host cell comprising the expression vector. In a further aspect, the invention relates to the use of any of theses materials for the preparation of a medicament for blocking apoptosis in a patient in need thereof.

Abstract: Cell aggregate formation control and cell aggregate disintegration control are carried out with respect to cells in a culture container to increase cell proliferation efficiency. The number of the cells in the culture container is counted without disassembly of a culture system and irrespective of the density of the cells. An external force is applied to the culture container to carry out at least one of cell aggregate formation control and cell aggregate disintegration control with respect to cells in the culture container, thus culturing the cells. The external force is applied to the culture container by pressing an agitating member onto a top surface of the culture container placed in flat orientation to a predetermined pressing degree, and moving the agitating member in a horizontal direction at a predetermined speed, thus controlling at least one of cell aggregate formation and cell aggregate disintegration with respect to the cells in the culture container.

Abstract: The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.

Abstract: Activation of HIV-1 replication causes oxidative stress, which in turn potentiates HIV-1 replication. The common basis for the compounds of the present invention is: A) the capacity of reactivating HIV-1 from latency, and B) the ability to counteract the cellular machinery which activates in order to limit the effects of oxidative stress. In this way, oxidative stress can be potentiated and a “chain reaction” is sparked. This “chain reaction” induces a more efficient reactivation of HIV-1 from latency and, in some cases, induces selective killing of the infected cells. Actions A) and B) can either be carried out by one drug exerting both effects, or obtained by the combined use of distinct drugs. There are two main cellular machineries counteracting oxidative stress, i.e. the thioredoxin (Trx) thioredoxin reductase (TrxR) system and glutathione. Herein, we present drug strategies capable of exerting action B) by blocking either of the two machineries.

Abstract: Ex-vivo prepared T-cells are harvested from cell culture conditions and formulated in medium suitable for infusion. The formulation is made by labeling the cells with one or more agents which have reactivity for T-cell surface moieties capable of delivery activation signals upon cross-linking and mixing the labeled cells with biodegradable nanospheres or microspheres coated with a material capable of cross-linking the agents attached to the T-cell surface moieties. Alternatively, the formulation may be made by mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials. The first material binds the second material and the second material has reactivity for surface moieties on the T-cells and the interaction of the second materials with the T-cells causes the activation of the T-cells.

Abstract: The invention provides CD4+CD25? T cells and Tr1-like regulatory T cells (i.e., contact-independent Type 1-like regulatory T cells), processes for their production and their use for regulatory purposes.

Abstract: The invention relates to a method for preparing antigen-specific Tr1 regulatory lymphocytes. The inventive method involves the use of artificial antigen-presenting cells expressing a molecule from the HLA class II system and a human LFA-3 molecule and expressing none of the B7-1, B7-2, B7-H1, CD40, CD23, or ICAM-1 costimulatory molecules.

Abstract: T-cells are generated with enhanced immunostimulatory capabilities for use in self therapy treatment protocols, by utilizing a biodegradable device with a biodegradable support that has one or more agents that are reactive to T-cell surface moieties. The biodegradable devices are mixed with the T-cells sufficiently so that the one or more agents cross-link with the T-cells' surface moieties and deliver a signal to the T-cells to enhance immunostimulatory capabilities.

Abstract: The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.

Abstract: Culture media comprising manganese and methods of culturing cells to improve sialylation and glycosylation of glycoproteins are provided.

Abstract: An objective of the present invention is to provide polynucleotides encoding insect desiccation resistance proteins, and uses thereof cDNA libraries were produced from Polypedilum vanderplanki larvae in a desiccated state, a P. vanderplanki EST database was constructed, and genes encoding LEA proteins were isolated. This resulted in the successful isolation of three types of novel gene encoding LEA-like proteins (PvLEA1, PvLEA2, and PvLEA3.) When secondary structure predictions and motif searches were performed on the proteins deduced from each of the genes, all three proteins had ?-helix-rich structures and LEA_4 motifs, which are characteristic of LEA proteins. Moreover, the recombinant proteins synthesized from PvLEA1, 2 and 3 genes were heat soluble even when boiling, so that PvLEA1, 2 and 3 proteins have highly hydrophilic property as well as plant LEA proteins. Therefore, the three isolated genes were found to be novel P. vanderplanki-derived LEA genes.

Abstract: Peptide vaccines against cancer are described herein. In particular, the present invention describes epitope peptides derived from INHBB that elicit CTLs. The present invention also provides established CTLs that specifically recognize HLA-A02 positive target cells pulsed with the peptides. Antigen-presenting cells and exosomes that present any of the peptides, as well as methods for inducing antigen-presenting cells are also provided. The present invention further provides pharmaceutical compositions containing the INHBB polypeptides or polynucleotides encoding thereof, as well as exosomes and antigen-presenting cells as active ingredients.

Abstract: 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.

Abstract: Disclosed herein are methods and compositions for increasing nuclease activity to increase nuclease-mediated genomic modifications.

Abstract: The present invention relates to polypeptides, preferably from Drosophila melanogaster (DmShaI) as target for insecticides.

Abstract: A method of promoting the regression of a cancer in a mammal comprising: (i) administering to the mammal nonmyeloablative lymphodepleting chemotherapy, and (ii) subsequently administering: (a) autologous T-cells, which have been previously isolated, selected for highly avid recognition of an antigen of the cancer, the regression of which is to be promoted, and rapidly expanded in vitro only once, and, either concomitantly with the autologous T-cells or subsequently to the autologous T-cells, by the same route or a different route, a T-cell growth factor that promotes the growth and activation of the autologous T-cells, or (b) autologous T-cells, which have been previously isolated, selected for highly avid recognition of an antigen of the cancer, the regression of which is to be promoted, modified to express a T-cell growth factor that promotes the growth and activation of the autologous T-cells, and rapidly expanded in vitro only once, whereupon the regression of the cancer in the mammal is promoted.

Abstract: The present invention relates to set overlapping immunogenic peptides of a variable antigen, and uses thereof, in particular for diagnostic and therapeutic purposes. The present invention relates also to a sub-population of CD8 T cells associated with the non-progressive status in HIV-infected subjects.

Abstract: First, to solve the problems of the present invention, the present inventors confirmed the presence of ovarian cancer antigen-specific T cells in the peripheral blood of ovarian cancer patients by using an experimental system that detects combinations of CD4 and IL-4 or IFN?. Next, using analogue peptides of the core protein MUC16 of the ovarian cancer-associated antibody C125, the present inventors revealed that antigen-specific CD4-positive T cells are present at an average frequency of about 4% in the peripheral mononuclear cells of patients and healthy subjects. Then, the present inventors analyzed the epitope for T cells in the core protein MUC16 of the ovarian cancer-associated antigen CA125, and determined the amino acid sequence FTLNFTITN (SEQ ID NO: 1) to be a shorter epitope. The present inventors further discovered that the analogue peptide OVCA11: GHTAPOPLLVPFTLNFTITN (SEQ ID NO: 11) is suitable for T cell activation.

Abstract: A process for damaging and maintaining damage to the nucleic acids of pathogens such as white blood cells, bacteria and viruses which may be contained in blood or blood components. This process comprises adding to the blood or blood component containing pathogens an effective amount of riboflavin, and exposing the fluid to light of an appropriate wavelength to damage the nucleic acid of the pathogen and to substantially maintain the damage to the pathogenic nucleic acids to allow for subsequent transfusion into a recipient.

Abstract: The present invention provides isolated T cell receptors (TCRs) having the property of specifically binding to the VYGFVRACL (SEQ ID NO:1)-HLA-A24 peptide-MHC. Such TCRs are useful, either alone or associated with a therapeutic agent, for targeting cancerous cells presenting the complex.

Abstract: According to the invention there is described a method for ex vivo immunization of humans and animals comprising the following steps of: a) isolating autologous tumor cells; b) treating the tumor cells to prevent the survival thereof following reinfusion; c) incubating the thus treated tumor cells with intact heterologous bispecific and/or trisepcific antibodies showing the following properties: ?—binding to a T cell; ?—binding to at least one antigen on a tumor cell; ?—binding, by their Fc portion (in the case of bispecific antibodies), or by a third specificity (in the case of trispecific antibodies) to Fc receptor-positive cells.

Abstract: A biodegradable device for activating T-cells includes a biodegradable support and a binder attached to the biodegradable support, the binder having reactivity to one or more agents capable of binding to a T-cell surface antigen.

Abstract: The invention provides for compositions, e.g., pharmaceutical compositions, comprising a T lymphocyte, or a population thereof, expressing at least one recombinant polynucleotide encoding a cytokine that enhances T lymphocyte survival during the contraction phase of an immune response. The invention further provides an isolated T lymphocyte, or population thereof, expressing at least one recombinant polynucleotide encoding the cytokine, wherein the polynucleotide comprises a non-native coding sequence encoding the cytokine. Also provided is the use of such compositions and T lymphocytes, or populations thereof, for the treatment or prevention of a medical condition e.g., cancer. A method of preparing the a T lymphocyte with enhanced T cell survival is further provided herein.

Abstract: The present invention describes diagnosis and treatment of antibody-mediated inflammatory auto-immune diseases. The biochemical mechanisms underlying such disorders are described as characteristic molecular markers and antibody-mediated ligand-receptor interactions. Specifically, the activation of T-cells by disease specific IgG binding to the IGF-1 receptor is shown to underlie thyroid associated ophthalmopathy associated with Graves' disease and rheumatoid arthritis. Diagnostics for detection of disease are provided, as are therapeutics based on the determination of the mechanisms underlying a particular pathology.

Abstract: T-cells are generated with enhanced immunostimulatory capabilities for use in self therapy treatment protocols, by utilizing a biodegradable device with a biodegradable support that has one or more agents that are reactive to T-cell surface moieties. The biodegradable devices are mixed with the T-cells sufficiently so that the one or more agents cross-link with the T-cells' surface moieties and deliver a signal to the T-cells to enhance immunostimulatory capabilities.

Abstract: The invention provides a novel method for generating stable mammalian cell lines with enhanced protein production capabilities, and to expression vectors and related methods for high level expression of biopharmaceutical proteins of interest.

Abstract: The present invention relates generally to methods for generating, expanding, and isolating antigen-specific T cells. Compositions of antigen-specific T cells activated and expanded by the methods herein are further provided.

Abstract: Cross-reactive T cells recognizing both MBP93-105 and HHV-61-13 peptides represent a significant subset of T cells with some degree of TCR degeneracy. It appears that the recognition of the cross-reactive T cells has a less stringent requirement for the flanking residues of the two peptides. In contrast, these flanking residues are critical for the T cell recognition of mono-specific T cells. The association between HHV-6 and autoreactive immune responses to MBP indicates that cross-reactive T cells, peptides from the V-D-J region of the T cell receptor from autoreactive T cells, and antiviral agents may prevent or treat MS.

Abstract: The present invention relates to the immunotherapB of cancer, in particular several tumor entities including hematological malignancies. The present invention relates to tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. In particular, the present invention relates to two novel peptide sequences derived from HLA class I or II molecules of human oncofoetal antigen immature laminin receptor (OFA/iLR), which can be used in vaccine compositions for eliciting anti-tumor immune responses.

Abstract: It is an object of the present invention to provide an immunodeficient animal capable of generating human-derived lymphoid cells, a human-derived lymphoid cell, and a method for producing a human antigen-specific antibody. The means for solving the aforementioned object is: an immature immunodeficient mammal into which human-derived hematopoietic precursor cells have been transplanted, and which is able to generate said human-derived hematopoietic cells or immunocompetent cells; and a method for producing a human-derived antibody, which is characterized in that it comprises recovering immunocompetent cells from the above-described mammal, culturing the immunocompetent cells, and collecting a human-derived antibody from the obtained culture product.