Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

Abstract: Methods for preventing or treating an IgE-mediated allergic disease in a patient are presented, the methods comprising administration of a monoclonal antibody capable of binding to a human CD40 antigen located on the surface of a human B cell, wherein binding of the antibody to the CD40 antigen prevents the growth or differentiation of the B cell. Monoclonal antibodies useful in these methods, and epitopes immunoreactive with such monoclonal antibodies are also presented.

Abstract: The present invention relates to methods for treating B cell lymphoma using CD80-specific antibodies.

Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

Abstract: Methods are provided to specifically modulate the trafficking of systemic memory T cells, particularly CD4+ T cells, without affecting naive T cells or intestinal memory T cells. It is shown that systemic memory T cells, which are characterized as CD45Ra?, and integrin ?4?7?, express high levels of CCR4. Ligands of CCR4, such as TARC or MDC, act as an adhesion trigger, wherein upon CCR4 binding, these cells undergo integrin-dependent arrest to the appropriate vascular receptor(s). This arrest acts to localize the cells at the target site. The methods of the invention manipulate this triggering, and CCR4 mediated chemotaxis, to affect the localization of T cells in targeted tissues. In an alternative embodiment, the agent is an antagonist that blocks CCR4 biological activity. An advantage of the invention is the selectivity for systemic memory T cells, without affecting native T cells or intestinal memory T cells.

Abstract: The present invention relates to the identification of a novel role of CXCR-4 in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of CXCR-4 in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for CXCR-4. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of CXCR-4 gene expression or the inhibition of CXCR-4 activity in transformed cells reverses the transformed phenotype.

Abstract: The present invention relates to a LO-CD2a antibody and methods of using such antibodies or molecules that bind to the same epitope (or a portion thereof) to prevent and inhibit an immune response in human patients, preferably, where the immune response is mediated by the activation and proliferation of T cells or natural killer cells. The administration of an effective amount of the LO-CD2a antibody to a human patient will prevent or inhibit graft rejection, graft versus host disease or autoimmune disease.

Abstract: The present invention relates to methods and compositions for the prevention and treatment of cancer, inflammatory diseases and disorders or deficiencies of the immune system. The methods of the invention comprise administering a CD40 binding protein that potentiates the binding of CD40 to CD40 ligand.

Abstract: Methods are provided for preventing the development of autoimmune diseases in susceptible subjects and for prolonging acceptance of tissue transplants by administration of an agonist of the T cell CD28 co-stimulatory receptor.

Abstract: Novel recombinant polypeptides are disclosed herein that include a CD4 polypeptide ligated at its C-terminus with a portion of an immunoglobulin comprising a hinge region and a constant domain of a mammalian immunoglobulin heavy chain. The portion of the IgG is fused at its C-terminus with a polypeptide comprising a tailpiece from the C-terminus of the heavy chain of an IgA antibody or a tailpiece from a C-terminus of the heavy chain of an IgM antibody. Also disclosed herein are methods for using these CD4-fusion proteins.

Abstract: Methods and compositions for treating or preventing fibrotic disorders, e.g., sclerotic disorders, for example scleroderma, using CD2-binding agents, e.g., LFA-3/IgG fusion polypeptides or LFA-3-binding agents, are provided.

Abstract: The present invention relates to methods for targeting antigen to antigen presenting cells through specific endocytic receptors, which results in persistent antigen presentation in the context of MHC molecules. Such highly efficient antigen presentation results in robust and long lasting immune responses, in particular cell mediated responses. The invention provides for immune compositions containing antibodies to DEC-205 in combination with the antigen for eliciting either T cell mediated immunity when delivered with a dendritic cell maturation factor, or for inducing tolerance when delivered in the absence of a dendritic cell maturation factor. The compositions described in the present invention are effective as a single dose at low concentrations and show efficacy even with non-replicating subunit vaccines.

Abstract: The present invention provides a method of treating autoimmune diseases. In particular, it provides a method for the treatment of ulcerative colitis comprising administering to a subject a therapeutically effective amount of a pharmaceutical formulation comprising an antibody, wherein said antibody binds to CD3.

Abstract: Recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses are disclosed. The recombinant molecules are comprised by at least one targeting unit and at least one antigenic unit connected through a dimerization motif. Also disclosed are nucleic acid molecules encoding the recombinant antibody-based molecule and methods of treating multiple myeloma or lymphoma in a patient using the recombinant antibody-based molecules or the nucleic acid molecules.

Abstract: The invention teaches the use of monoclonal antibodies being specific for CD28 and activating T lymphocytes of several to all sub-groups without an occupation of an antigen receptor of the T lymphocytes and thus in an antigen-unspecific manner, or of an analogue hereto, for the preparation of a pharmaceutical composition for stimulating blood cells not carrying CD28, and for treating diseases with a reduced number of such blood cells.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the transporter peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the transporter peptides, and methods of identifying modulators of the transporter peptides.

Abstract: The invention relates to a humanized anti-B7-2 antibody that comprises a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.

Abstract: A method for controlling a flavivirus entry into a cell, kits for assaying the flavivirus entry into the cell, and methods of treating and preventing flaviviruses infections are disclosed, together with vaccine and pharmaceutical compositions.

Abstract: The present invention relates generally to methods for activating and expanding cells, and more particularly, to a novel method to activate and/or stimulate cells that maximizes the expansion of such cells to achieve dramatically high densities. In the various embodiments, cells are activated and expanded to very high densities in a short period of time. In certain embodiments, cells are activated and expanded to very high numbers of cells in a short period of time. Compositions of cells activated and expanded by the methods herein are further provided.

Abstract: The present invention provides an isolated or recombinant HLA-DQ restricted T-cell receptor or functional equivalent and/or fragment thereof capable of recognizing a prolamine-derived peptide. The present invention also provides isolated, recombinant or synthetic prolamine-derived peptides involved in food-related immune enteropathy. In yet another embodiment the invention provides a diagnostic kit comprising an isolated or recombinant HLA-DQ restricted T-cell receptor according to the invention or host cell comprising a T-cell receptor according to the invention or an antibody according to the invention and a suitable means of detection. Such a diagnostic kit is, for example, very useful for detecting in food, food components or samples from (suspected) patients the presence of prolamine-derived peptide involved in food-related immune enteropathy (for example: celiac sprue, tropical sprue, giardiasis or food allergies of childhood).

Abstract: The present invention relates to, inter alia, methods for inhibiting the interaction of the B-lymphocyte antigen, B7-2, with its natural ligand on the surface of an immune cell are disclosed. The methods comprise contacting the immune cell with an agent which inhibits B7-2 binding with its natural ligand, to thereby inhibit the interaction. Examples of such agents are provided, and include a soluble form of B7-2, an antibody that recognized B7-2. The method may also include contacting the immune cell with an agent that blocks the interaction of B7-1 with its natural ligand. Further, the method may include contacting the immune cell with an immunomodulating agent, for example, an antibody reactive with CD28, an antibody reactive with CTLA4, an antibody reactive with a cytokine, a CTLA4Ig fusion protein, a CD28Ig fusion protein, and an immunosuppressive drug. Both in vivo and in vitro applications of the method are disclosed.

Abstract: The present invention relates to methods for the treatment and diagnosis of immune related diseases, including those mediated by cytokines released primarily either Th1 or Th2 cells in response to antigenic stimulation. The present invention further relates to methods for biasing the differentiation of T-cells in either the Th1 subtype or the Th2 subtype, based on the relative expression levels of the gene TCCR, and its agonists or antagonists. The present invention further relates to a method of diagnosing Th1- and Th2-mediated diseases.

Abstract: The invention relates to a polyclonal population of bispecific molecules which comprises a plurality of different bispecific molecules, each comprising a first antigen recognition portion that binds a C3b-like receptor cross-linked to a different second antigen recognition portion that binds a pathogenic antigenic molecule such that the plurality of different bispecific molecules have different second antigen recognition portions with different recognition specificities, such as with recognition specificities directed to different epitopes and/or different variants of a pathogen and/or to different pathogens. The invention also relates to methods of producing such polyclonal population of bispecific molecules. The invention further relates to methods of using such polyclonal population of bispecific molecules for the clearance of pathogens from the circulatory system of a mammal.

Abstract: A new class II cytokine receptor has been identified, which comprises an interleukin-22 receptor molecule, and an interleukin-20 receptor &bgr; molecule. The complex binds to cytokines homologous to IL-10, including mda-7 and IL-20. Also described are methods for inhibiting effect of interleukin-20, mda-7, and IL-19 on cells. The latter is especially useful in treatment of, e.g., skin diseases such as psoriasis.

Abstract: The invention relates to macrophages which have at least one of the following properties: their cytotoxic activity without IFN-&ggr; is increased by about 20 to 30% with respect to standard macrophages, and is preferably of about 70%; their cytotoxic activity with IFN-&ggr; is increased by about 20 to about 40% with respect to standard macrophages, and is preferably of about 93%; the extension of the deactivation of the cytotoxic activity in reply to an activation of IFN-&ggr; is in a ratio such that after 60h of activation with IFN-&ggr;, the cytotoxic activity is higher than or equal to 30%, preferably of about 55%, compared to the maximum cytotoxic activity presented by the macrophages due to IFN-&ggr; activation, with said cytotoxic activity being measured as the percentage of inhibition of 3-H thymidine incorporation by target tumoral cells, particularly U 937 cells.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucelotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: The present invention relates to the treatment, inhibition and prevention of cancer by the administration of anti-C3b(i) antibodies. The invention also relates to the treatment, inhibition and prevention of cancer by the administration of IgM antibodies and/or complement components prior to the administration of anti-C3b(i) antibodies. The present invention further relates to the detection, imaging, diagnosis and monitoring of cancer utilizing C3b(i) specific antibodies.

Abstract: Disclosed herein are therapeutic compositions containing agents that modulate the immune response in a patient.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and a therapeutic and/or diagnostic agent. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates compositions in therapeutic and/or diagnostic methods.

Abstract: Provided are methods of enhancing and maintaining immune tolerance by modulation of CD200 or CD200R. Provided are antagonists thereof including antibodies.

Abstract: The use of a chimeric anti-CD20 antibody, RITUXAN®, as an in vivo or in vitro purging agent, of patients receiving bone marrow or peripheral blood stem cell transplant during treatment of B-cell-related malignancies, e.g., B-cell lymphomas or leukemias, is disclosed. Such purging may enhance engraftment and/or prevent disease relapse in such patients.

Abstract: The invention identifies PD-1 as a receptor for B7-4. B7-4 can inhibit immune cell activation upon binding to an inhibitory receptor on an immune cell. Accordingly, the invention provides agents for modulating PD-1, B7-4, and the interaction between B7-4 and PD-1 in order to modulate a costimulatory or an inhibitory signal in a immune cell resulting in modulation of the immune response.

Abstract: Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Abstract: The present invention provides liquid formulations of antibodies or antibody fragments that immunospecifically bind to integrin &agr;V&bgr;3, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention provides liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin &agr;V&bgr;3, which formulations are substantially free of surfactant, inorganic salts, and/or other common excipients. Furthermore, the invention provides methods of preventing, treating or ameliorating an inflammatory disorder, an autoimmune disorder, a disorder associated with aberrant expression and/or activity of integrin &agr;V&bgr;3, a disorder associated with abnormal bone metabolism, a disorder associated with aberrant angiogenesis or cancer utilizing the liquid formulations of the present invention.

Abstract: The present invention provides liquid formulations of antibodies or antibody fragments that immunospecifically bind to integrin &agr;v&bgr;3, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention provides liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin &agr;v&bgr;3, which formulations are substantially free of surfactant, inorganic salts, and/or other common excipients. Furthermore, the invention provides methods of preventing, treating or ameliorating an inflammatory disorder, an autoimmune disorder, a disorder associated with aberrant expression and/or activity of integrin &agr;v&bgr;3, a disorder associated with abnormal bone metabolism, a disorder associated with aberrant angiogenesis or cancer utilizing the liquid formulations of the present invention.

Abstract: The invention relates to novel nucleic acid sequences which encode human autoantibodies and antiidiotypic antibodies against blood platelet membrane proteins, to novel amino acid sequences of human antibodies, and to their use for the diagnosis and therapy of diseases.

Abstract: The present application describes therapy with antagonists which bind to B cell surface markers, such as CD20. In particular, the application describes the use of such antagonists to treat autoimmune disease in a mammal who experiences an inadequate response to a TNF&agr;-inhibitor.

Abstract: A method for transfecting T cells with a nucleic acid molecule comprising a gene such that the gene is expressed in the T cells is described. The T cells are stimulated and proliferating prior to introduction of the nucleic acid molecule.

Abstract: Novel aglycosylated antibodies having a binding affinity for the CD3 antigen complex are of value for use in therapy, particularly in immunosuppression.

Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.

Abstract: Immunization of human antibody-producing transgenic mice, which have been created using genetic engineering techniques, with AILIM molecule as an antigen resulted in various human monoclonal antibodies capable of binding to AILIM and capable of controlling a variety of biological reactions (for example, cell proliferation, cytokine production, immune cytolysis, cell death, induction of ADCC, etc.) associated with AILIM-mediated costimulatory signal (secondary signal) transduction. Furthermore, it has been revealed that the human monoclonal antibody is effective to treat and prevent various diseases associated with AILIM-mediated costimulatory signal transduction, being capable of inhibiting the onset and/or advancement of the diseases.

Abstract: Methods and compositions useful for inducing a cytotoxic T lymphocyte response (CTL) in a human or domesticated or agriculturally important animal. The method includes the steps of providing the antigen to which the CTL response is desired and providing a microfluidized antigen formulation which comprises, consists, or consists essentially of two or more of a stabilizing detergent, a micelle-forming agent, and an oil. This antigen formulation is preferably lacking, in an immunostimulating peptide component, or has sufficiently low levels of such a component that the desired CTL response is not diminished. This formulation is provided as a stable oil-in-water emulsion.

Abstract: The present invention is directed to an immune complex composition, and a method of using that complex to enhance an in viva immune response against a preselected target antigen. The immune complexes of the present invention comprise a monoclonal antibody specific for binding to complement receptor (CR2) site on B lymphocytes linked to a target antigen. As shown in FIG. SA-SD immune complexes bound to monkey B cells are removed in concert with loss of CR2. FIGS. SA and SB demonstrate the % AI488 HB135 and % APhCy CD21 positive cells, out of the doubly positive FE CD20/PerCF CD45 population over time, after injection of A1488 labeled HB135 (an anti-CR2 antibody, administration indicated by first arrow) followed by injection of rabbit anti-mouse IgG (administration indicated by the second arrow). FIGS. SC and SD are plots of the molecules of equivalent soluble fluorochome (MESF) values for these populations.

Abstract: Methods for inhibiting intimal hyperplasia in the vasculature of mammals, including primates, are disclosed. The methods comprise administering to the mammal an anti-PDGF receptor antibody, such as an anti-PDGF-alpha receptor antibody or an anti-PDGF-beta receptor antibody. The methods are useful in reducing intimal hyperplasia due to, for example, vascular injuries resulting from angioplasty, endarterectomy, reduction atherectomy or anastomosis of a vascular graft. The anti-PDGF receptor antibodies may optionally be administered coordinately with heparin, whereby the coordinately administered antibody and heparin are combinatorially effective in inhibiting intimal hyperplasia.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc&ggr;RIIB, particularly human Fc&ggr;RIIB, with greater affinity than said antibodies or fragments thereof bind Fc&ggr;RIIA, particularly human Fc&ggr;RIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Abstract: The method of immunotherapy of the present invention involves the regulation of the T cell immune response through the activation or suppression/inactivation of the CD28 pathway. Induction of activated T cell lymphokine production occurs upon stimulatory binding of the CD28 surface receptor molecule, even in the presence of conventional immunosuppressants. Inhibition of CD28 receptor binding to an appropriate stimulatory ligand or inactivation of the CD28 signal transduction pathway through other means down-regulates CD28-pathway related T cell lymphokine production and its resulting effects.

Abstract: Methods are provided for reducing the number of HIV-infected cells or HIV infection-susceptible cells of a host. Therapeutically this is achieved by exposing the cells to a V region selective element (VRSE) which binds to T cell receptors (TCR) of a V region defined family (VRDF) that is preferentially infected with HIV. The therapeutic VRSE can be an antibody which binds to the VRDF and is capable of causing cytotoxicity of infected and infection-susceptible cells, either alone, in conjunction with host factors, or fused to a toxin. The number of HIV-infection susceptible cells can be reduced prophylactically and in some circumstances therapeutically by immunization with an antibody or T cell receptor that induces an immune response that includes antibodies that bind to the TCR of a VRDF associated with HIV infection. The latter antibodies inhibit the viability of the infected or infection-susceptible cell.

Abstract: A method is provided for producing a population of substantially purified CD4+ Th2 lymphocytes. The method includes stimulating a population of substantially purified CD4+ T cells isolated from a subject by contacting the population with an immobilized anti-CD3 monoclonal antibody and an immobilized antibody that specifically binds to a T cell costimulatory molecule in the presence of a Th2 supportive environment to form a stimulated population of T cells. Purified populations of Th2 cells are disclosed herein, as are methods for their use. For example, substantially purified CD4+ Th2 lymphocytes can be used to treat graft-versus-host-disease, tumors, and autoimmune disorders.

Abstract: The present invention is based, at least in part, on the finding that tolerance can be induced by inhibition of CD4+ and CD8+ T cells. Accordingly, the methods of the invention are useful in treating a primate, e.g., a human, by inhibiting CD4+ and CD8+ T cells to induce tolerance to at least one antigen, e.g., self or foreign, such as for inducting tolerance in a primate against a transplanted antigen, e.g., an allogeneic or xenogeneic transplanted antigen.

Abstract: The present invention provides a novel lymphocyte inhibitory receptor termed BTLA which is expressed on both T and B cells, and identifies B7 family member B7x as interacting with BTLA to attenuate lymphocyte activity. Methods and compositions for modulating BTLA-mediated negative signaling and interfering with the interaction of BTLA and B7x for therapeutic, diagnostic and research purposes are also provided.