Abstract: Methods to inhibit the formation of retrovirus integrase reaching dimers, to dissociate retrovirus integrase reaching dimers, and to stabilize retrovirus integrase reaching dimers in a conformation in which retrovirus DNA-to host cell DNA integration activity of the integrase is inhibited are provided. Methods for treating a retrovirus infection, which target retrovirus integrase reaching dimer formation and/or stability are also provided.

Abstract: This invention relates to culture-expanded T suppressor cells derived from CD25?CD4+ T cells, and their use in modulating immune responses. This invention provides methods of producing culture-expanded T suppressor cells, which are antigen specific, and their use in modulating autoimmune diseases and transplantation rejection.

Abstract: A method for generating/expanding in vitro a CD4+CD25+ T regulatory (Tr) cell and the use thereof in the treatment of diseases associated with a cell-mediated immune response (including T- and antibody-mediated responses).

Abstract: The present invention relates specific activation of a regulatory T cell via a specific CD4 epitope and uses thereof, e.g. for the treatment of an autoimmune disease or an allergy or asthma or graft rejection or tolerance induction.

Abstract: The invention involves the discovery that if dendritic cells loaded with a tumor antigen are cultured in interleukin-15 (IL-15), or if T cells activated by the dendritic cells are cultured in IL-15, Treg activity that is specific for the tumor antigen is reduced. This reduction in Treg activity results in an increase in anti-tumor immune response. Another embodiment of the invention involves the discovery that incubating dendritic cells with a MAP kinase inhibitor in combination with IL-15 gives synergistic benefits when the dendritic cells are used to activate T cells. Dendritic cell and T cell compositions incubated with IL-15 or a MAP kinase inhibitor are provided.

Abstract: Methods for stably transfecting mammalian natural killer cells comprising: transfecting a packaging cell line with a retroviral expression vector; culturing the transfected packaging cell line in a cell culture medium; and culturing the mammalian natural killer cells with the cell culture medium. Natural killer cells transfected according to the disclosed methods are also provided.

Abstract: The present invention provides a blood analyzer and a blood analyzing method capable of obtaining information regarding B lymphocytes and T lymphocytes without using a fluorescence-labeled antibody. The blood analyzer of the present invention includes a blood specimen supplying portion, a sample preparation portion that prepares a measurement sample without using a fluorescence-labeled antibody by mixing a blood specimen supplied from the blood specimen supplying portion, a hemolyzing agent, and a fluorescent dye that stains nucleic acid, a light source, a first detector that detects fluorescence, a second detector that detects scattered light, and information processing portion that classifies lymphocytes based on the intensity of fluorescence and scattered light, and based on the fluorescence intensity of the classified lymphocytes, obtains information regarding B-lymphocytes and T-lymphocytes.

Abstract: The present invention encompasses a method for expanding an antigen specific T cell from a population of cells. The method of the present invention comprises contacting a population of cells with an MHC restricted antigenic glypican-3 peptide. In some instances, the T cell is expanded using monocyte-derived dendritic cells and defined MHC restricted antigenic glypican-3 peptides. In one embodiment, high-affinity antigen-specific T-cell receptors (TCRs) can be cloned from the antigen specific T cell.

Abstract: The present invention provides dendritic cells capable of efficiently activating and/or proliferating ?? T-cells in vivo and/or in vitro, pharmaceutical compositions comprising said dendritic cells, therapeutic methods and ?? T-cell culture methods utilizing said dendritic cells. By pulsing immature dendritic cells derived from peripheral blood monocytes with a bisphosphonate-based bone metabolism improving drug to enable the cells to activate ?? T-cells, and cultivating them with a cell subset containing ?? T-cells, ?? T-cells can be activated and/or proliferated. This allows for easy proliferation of ?? T-cells without burdening a patient, leading to practical applications of immune cell therapies that utilize ?? T-cells.

Abstract: The present invention relates to human secreted polypeptides, and isolated nucleic acid molecules encoding said polypeptides, useful for diagnosing and treating diseases, disorders, and/or conditions (such as immune, cardiovascular, cancer, and other proliferative diseases, disorders, and/or conditions) related to said human secreted proteins. Antibodies that bind these polypeptides are also encompassed by the present invention. Also encompassed by the invention are vectors, host cells, and recombinant and synthetic methods for producing said polynucleotides, polypeptides, and/or antibodies. The invention further encompasses screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further encompasses methods and compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.

Abstract: The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human maligancy.

Abstract: A human T cell population which has both cytotoxic and immunosuppressive activities, is efficiently produced by first fractionating CD2-positive CD14-negative cells from mononuclear cells collected from a human umbilical cord blood, and then co-culturing them with stromal cells. The resulting blast cells, which have the desired activity, are proliferated by further culture.

Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.

Abstract: In accordance with one aspect of the present invention, methods have been developed for identifying compositions which support the culture of defined cell populations. In accordance with another aspect of the present invention, methods have been developed for identifying compositions which promote differentiation of defined cell populations. In accordance with yet another aspect of the present invention, methods have been developed for identifying compositions which induce apoptosis of defined cell populations. In accordance with still another aspect of the present invention, methods have been developed for identifying compositions which promote cell senescence of defined cell populations. In accordance with still another aspect of the present invention, methods have been developed for identifying media which modulate the retardation of cell growth of defined cell subpopulation(s).

Abstract: Described are (a) parvovirus variants capable of propagating and spreading through human tumor cells which is obtainable by serially passaging a rodent parvovirus as starting strain in semi-permissive human tumor cells, and (b) parvovirus variants capable of propagating and spreading through human tumor cells characterized by particular amino acid deletions and/or substitutions, e.g. a deletion of several amino acids in the C-terminus of NS1/middle exon of NS2. A pharmaceutical composition containing such parvoviruses as well as their use for the treatment of cancer, preferably a glioblastoma, is also described.

Abstract: The invention features methods for inhibiting enhancement of expression of a FoxP3 gene in a cell, methods for inhibiting induction of differentiation of a cell into a regulatory T cell, methods for reducing immunosuppression, methods for stimulating tumor immunity, and methods for treating a patient with a tumor. The methods of the invention involve suppressing function of an FSTL1 protein in the cell. In the methods of the invention, function of an FSTL1 protein in the cell may be suppressed using an anti-FSTL1 antibody.

Abstract: The present invention relates to an isolated Tr1-like cell population capable of producing IL-13, the population having immunosuppressive activities; methods for identifying/isolating/enriching the population and its uses thereof.

Abstract: According to the present invention, there are provided a method for producing a human T cell, which comprises the steps of inducing an iPS cell from a human T cell, and differentiating the iPS cell into a T cell; a pharmaceutical composition comprising the T cell produced by the method; and a method for cell-based immunotherapy using the method.

Abstract: An in vitro assay is provided for determining the effect of an immune cell on a cell from an infectious or neoplastic disease. Also provided is an in vitro assay for determining the effect of an activated CD8+ T-cell on a sensitized melanoma cell. A method for improving the specific cytolytic activity (SCA) of an immune cell comprising contacting an immune cell with an antigen and an antigen-independent pro-inflammatory agent is provided. A method for ex vivo expansion of antigen-specific CD8+ T-cells with enhanced specific cytolytic activity (SCA) comprising culturing the antigen-specific CD8+ T-cells in a suitable culture media comprising an amino acid. An in vitro assay is provided for determining the effect of an immune cell on a cell from an infectious or neoplastic disease. A method of treating a subject suffering from an infectious or neoplastic disease with immuno therapy is described.

Abstract: A method of increasing the percentage of mouse and human Tregs is provided comprising providing B.fragilis or PSA and vitamin D or vitamin D metabolite to said mouse or human. Also, a method for treating inflammatory bowel diseases in an individual is presented where the individual is given a combination of vitamin D and B. fragilis or PSA. Such a treatment may be particularly effective in individuals who are either Vitamin D insufficient or deficient.

Abstract: The present invention is directed a method for the generation and/or expansion of CIK cell and/or NK cells by culturing peripheral blood cells in the presents of cytokines. The cytokines used in the method comprise interleukin 15 (IL-15) and interleukin 7 (IL-7), possibly in combination with further cytokines like interleukin 2 (IL-2) stem cell factor (SCF) and Fms-related tyrosine kinase 3 ligand (FLT3 ligand).

Abstract: The invention provides a method of promoting regression of a cancer in a mammal comprising (i) culturing autologous T cells; (ii) expanding the cultured T cells; (iii) administering to the mammal nonmyeloablative lymphodepleting chemotherapy; and (iv) after administering nonmyeloablative lymphodepleting chemotherapy, administering to the mammal the expanded T cells, wherein the T cells administered to the mammal are about 19 to about 35 days old and have not been screened for specific tumor reactivity, whereupon the regression of the cancer in the mammal is promoted.

Abstract: A polypeptide comprising a polypeptide consisting of an amino acid sequence shown in SEQ ID NO: 5 of Sequence Listing or a polypeptide consisting of an amino acid sequence having deletion, addition, insertion or substitution of one to several amino acid residues in the sequence, the polypeptide being capable of constituting an HLA-A24-restricted, MAGE-A4143-151-specific T cell receptor together with a polypeptide consisting of an amino acid sequence shown in SEQ ID NO: 2 of Sequence Listing.

Abstract: The present invention relates to new methods to promote sialylation of glycoconjugates, including recombinant glycoproteins, in glycoconjugate production systems. The invention relates to methods to promote efficient glycoconjugate sialylation in recombinant expression systems, by providing simpler and more economical ways to produce large intracellular pools of sialic acid precursors. The invention is directed to nucleic acids, vectors, and cells harboring vectors comprising nucleic acids encoding enzymes involved in the synthesis of sialic acid precursors, and cells harboring these nucleic acids in combination with nucleic acids encoding glycosyltransferases, including sialyltransferases, to facilitate the production of humanized recombinant glycoproteins in bacterial, fungal, plant, and animal cell expression systems.

Abstract: Compositions and methods are provided for the treatment of cancer. An immune effector cell population is pre-infected with an oncolytic virus. The combined therapeutic is safe and highly effective, producing an enhanced anti-tumor effect compared to either therapy alone. The methods of the invention thus provide for a synergistic effect based on the combined biotherapeutics.

Abstract: This invention provides a cell presenting at least one T cell receptor (TCR) anchored to the membrane by a transmembrane sequence, said TCR comprising an interchain disulfide bond between extracellular constant domain residues which is not present in native TCRs.

Abstract: A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect.

Abstract: Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain, as well as polynucleotides encoding same. Fusion proteins comprising cleavage half-domains are used in pairs to reconstitute a functional cleavage domain. In these fusion proteins, the zinc finger domain can be N-terminal to the cleavage half-domain, or the cleavage half-domain can be N-terminal to the zinc finger domain.

Abstract: The present invention provides a method for activating a Natural Killer (NK) cell by contacting the NK cell in vitro with an activating tumour cell preparation (ATCP). The invention also provides an activated NK cell produced by such a method and its use in the treatment of cancer.

Abstract: The present invention provides methods and materials by which glycosylation of glycoproteins can be regulated. Methods include the monitoring and regulation of parameters such that a glycoprotein having a desired product quality is obtained.

Abstract: Cytotoxic ?? T cells form an essential component in immunity to infections and tumors, and are also implicated in host defense against these challenges. The present disclosure demonstrates the ability of activated ?? T cells to cross-present exogenous antigens to CD8+ ?? T cells, a process previously thought to be mediated best by dendritic cells. In particular, the present disclosure provides a method for cross-presentation of antigen derived from tumor cell or microbial organisms such as viruses, bacteria, yeasts, parasites, and the like, or from cells infected with such organisms, to a CD8+ ?? T cell. Still further, the present disclosure provides a method for treatment of a tumor or a chronic or recurrent infectious disease, comprising delivering an antigen-presenting autologous ?? T cell population above into a patient requiring such treatment. Still yet further, a method is described for preparing a peptide-specific effector T cell.

Abstract: The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Abstract: A method for generating a purified regulatory T cell composition having a CD4+CD25+Foxp3? phenotype from naive T cells having CD4+CD45RA+RO?CD11alo CD27+ phenotype comprising the steps of stimulating a T cell receptor on the naive T cells and stimulating ICAM-1 on the naive T cells.

Abstract: The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human maligancy.

Abstract: A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways.

Abstract: A method resulting in differentiation of T-cells for use in cell therapy includes labeling the T-cells with a first array of antibodies specific for T-cell surface antigens; applying a universal cross-linking agent to the labeled T-cells with the first array of antibodies; labeling the T-cells with a second array of antibodies specific for T-cell surface antigens; and applying a universal cross-linking agent to the labeled T-cells with the second array of antibodies.

Abstract: The present invention encompasses methods, and kits for the isolation and expansion of T regulatory cells having the CD45RA+ phenotype, including such cells from human umbilical cord blood.

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 invention provides nucleic acids comprising a nucleotide sequence encoding programmed death ligand-1 (PD-L1) and a nucleotide sequence encoding a fusion protein comprising thymidylate kinase (TMPK) or a variant thereof and a cell surface marker or a variant thereof. Recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and kits relating to the nucleic acids are disclosed. Methods of treating or preventing a disease in a host and methods of suppressing an immune system in a host are also disclosed.

Abstract: The present invention is directed to a synthetic nucleic acid sequence which encodes a protein wherein at least one non-common codon or less-common codon is replaced by a common codon. The synthetic nucleic acid sequence can include a continuous stretch of at least 90 codons all of which are common codons.

Abstract: A T cell receptor (TCR) having the property of binding to the gp100 YLEPGPVTA peptide-HLA-A2 complex and comprising a TCR alpha variable domain and/or a TCR beta variable domain, characterized in that the domains are mutated relative to a TCR having the extracellular alpha and beta chain sequences SEQ ID NOs: 2 and that the TCR has a binding affinity for, and/or a binding half-life for, the YLEPGPVTA-HLA-A2 complex at least double that of a reference TCR. Embodiments of the invention such as the use of such TCRs in adoptive therapy, and fusions of such TCRs with therapeutic agents are also described.

Abstract: The invention relates to compositions of vault complexes containing recombinant cytokine fusion proteins that include a cytokine and a vault targeting domain, and methods of using the vault complexes to deliver the cytokines to a cell or subject, and methods for using the compositions to treat cancer, such as lung cancer.

Abstract: Disclosed are cells, methods of modulating cells, and therapeutic uses of the cells for the immune modulation of mammals in need thereof. Immune modulation including alteration of cytokine profile, cytotoxic activity, antibody production and inflammatory states is achieved through the administration of various cell types that have been unmanipulated or manipulated in order to endow specific biological activity. Cellular subsets and administration of the subsets in combination with various agents are also provided. One embodiment teaches the previously unknown finding that adipose tissue derived mononuclear cells contain T cells with immune regulatory properties that alone or synergistically with various stem cells induce immune modulation upon administration. Another embodiment is the finding that stimulation of stem cell activation results in stem cell secondary activation of immune modulatory cells, one type which is T regulatory cells (Tregs).

Abstract: T-cell receptors that recognize MART-1 antigen are provided. The TCRs can be used, for example, to treat patients suffering from melanoma.

Abstract: A method of producing lymphocytes characterized by comprising the step of culturing lymphocytes in the presence of a modified recombinant fibronectin fragment which has overlapping parts of the heparin-binding domain of fibronectin. This method makes it possible to achieve a high cell proliferation rate. The lymphocytes obtained thereby are appropriately usable in, for example, adoptive immunotherapy and, therefore, expected as highly useful in the clinical field. Moreover, a novel modified recombinant fibronectin fragment is provided.

Abstract: The present invention provides therapeutic and prophylactic compositions for use in treating and preventing disorders involved epithelial cell apoptosis, such as gastrointestinal disorders (e.g., inflammatory bowel disease, Crohn's disease or ulcerative colitis) in a subject, such as a human patient.

Abstract: An inexpensive, easily available, and convenient method of treating or preventing a virus infection is provided. The present invention relates to a method for the treatment or prevention of virus infections using polybiguanide-based compounds administering a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof The invention relies on the unique biochemical reaction in which polybiguanide-based compounds interfere with the spread of virus within or between organisms. The compositions and formulations described in the present invention are effective means to reduce the infectivity of the human immunodeficiency virus type 1 (HIV-1), and human herpes simplex viruses, and also to kill the causative organisms of many other sexually transmitted diseases (STDs).

Abstract: LAT (Linker for Activation of T-cells) is a protein involved in signaling through the T-cell receptor (TCR). The invention provides a LAT protein including mutations at ubiquitylation sites that result in an increase in stability of LAT in stimulated and unstimulated cells, and enhanced signaling through the TCR. The invention further provides use for a LAT protein including mutations at ubiquitylation sites for therapeutic and laboratory methods.

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.