Abstract: Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single VH or VK domain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen.

Abstract: Disclosed are methods of isolating and using a population of FOXP3+ regulatory T cells in a variety of preventative and therapeutic approaches to autoimmune diseases, graft-versus-host disease and transplant rejection.

Abstract: A method to increase the efficiency of transduction of hematopoietic and other cells by retroviruses includes infecting the cells in the presence of fibronectin or fibronectin fragments. The fibronectin and fibronectin fragments significantly enhance retroviral-mediated gene transfer into the cells, particularly hematopoietic cells including committed progenitors and primitive hematopoietic stem cells. The invention also provides improved methods for somatic gene therapy capitalizing on enhanced gene transfer, hematopoietic cellular populations, and novel constructs for enhancing retroviral-mediated DNA transfer into cells and their use.

Abstract: This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.

Abstract: The invention relates to novel artificial antigen presenting cells (aAPCs). The aAPC comprises at least one stimulatory ligand and at least one co-stimulatory ligand where the ligands each specifically bind with a cognate molecule on a T cell of interest, thereby mediating expansion of the T cell. The aAPC of the invention can further comprise additional molecules useful for expanding a T cell of interest. The aAPC of the invention can be used as an “off the shelf” APC that can be readily designed to expand a T cell of interest. Also, the aAPC of the invention can be used identify the stimulatory, co-stimulatory, and any other factors that mediate growth and expansion of a T cell of interest. Thus, the present invention provides powerful tools for development of novel therapeutics where activation and expansion of a T cell can provide a benefit.

Abstract: The present invention relates to humanized immunoglobulins, mouse monoclonal antibodies and chimeric antibodies that have binding specificity for human CD52. The present invention further relates to a humanized immunoglobulin light chain and a humanized immunoglobulin heavy chain. The invention also relates to isolated nucleic acids, recombinant vectors and host cells that comprise a sequence which encodes a humanized immunoglobulin or immunoglobulin light chain or heavy chain, and to a method of preparing a humanized immunoglobulin. The humanized immunoglobulins can be used in therapeutic applications to treat, for example, autoimmune disease, cancer, non-Hodgkin's lymphoma, multiple sclerosis and chronic lymphocytic leukemia.

Abstract: It is disclosed herein that isolated lymphocytes, such as human B-cells and CD4+ T-cell can be used to determine an amount of lymphocyte-associated anthrax lethal toxin activity present. Methods of using isolated lymphocytes to identify anthrax therapeutic agents and to determine the efficacy of a potential anthrax therapeutic are disclosed. Methods are also provided for diagnosing and treating anthrax infections.

Abstract: This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide 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 invention relates to BTLA antibodies that block BTLA-HVEM interaction and uses thereof.

Abstract: The present disclosure relates to CTLA4 proteins and uses of such proteins, for example to treat diseases associated with the dysregulation of immune responses.

Abstract: The present invention provides novel human sequence antibodies against human CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies.

Abstract: The present invention provides to a humanized monoclonal antibody having immunostimulatory effects. This antibody binds specifically to B lymphoblastoid cells, induces proliferation and activation of peripheral blood lymphocytes, particularly T cells, and is capable of eliciting an anti-tumor effect upon administration to subjects suffering from an immune deficiency.

Abstract: The invention provides various antibodies that bind to lymphotoxin-?, methods for making such antibodies, compositions and articles incorporating such antibodies, and their uses in treating, for example, an autoimmune disorder. The antibodies include murine, chimeric, and humanized antibodies.

Abstract: A human IgM monoclonal antibody responding to HIV-infected cells too, which is characterized by lysing activated human lymphocytes, etc. under the mediation by a homologous human complement, is obtained. Using the thus obtained monoclonal antibody, it is intended to provide an immune reaction controlling remedy, etc. containing the human IgM monoclonal antibody which responds specifically to activated lymphocytes and induces cell lysis under the mediation by a homologous complement. Using the human IgM monoclonal antibody responding to activated human lymphocytes, it is also intended to provide an HIV remedy, etc. characterized by lysing and eliminating activated lymphocytes to thereby treat transplantation rejection and autoimmune diseases caused by an over-response of T lymphocytes as well as HIV infection.

Abstract: The present invention provides compositions and methods for effectuating the localized expression of anti-CTLA-4 antibody proximal to a target tissue in a patient.

Abstract: It is disclosed herein that isolated lymphocytes, such as human B-cells and CD4+ T-cell can be used to determine an amount of lymphocyte-associated anthrax lethal toxin activity present. Methods of using isolated lymphocytes to identify anthrax therapeutic agents and to determine the efficacy of a potential anthrax therapeutic are disclosed. Methods are also provided for diagnosing and treating anthrax infections.

Abstract: The present invention provides to a humanized monoclonal antibody having immunostimulatory effects. This antibody binds specifically to B lymphoblastoid cells, induces proliferation and activation of peripheral blood lymphocytes, particularly T cells, and is capable of eliciting an anti-tumor effect upon administration to subjects suffering from cancer.

Abstract: The present invention provides to a humanized monoclonal antibody having immunostimulatory effects. This antibody binds specifically to B lymphoblastoid cells, induces proliferation and activation of peripheral blood lymphocytes, and is capable of eliciting an anti-tumor effect upon administration to subjects suffering from cancer.

Abstract: There is disclosed a polypeptide (CD40-L) and DNA sequences, vectors and transformed host cells useful in providing CD40-L polypeptides. More particularly, this invention provides isolated human and murine CD40-L polypeptides that bind to the extracellular binding region of a CD40 receptor.

Abstract: A polypeptide (8F4 molecule) with a T-cell costimulating biological activity is disclosed, as well as monoclonal antibodies against said 8F4 molecule and hybridoma cells which produce the monoclonal antibodies, the use as medicaments of substances which inhibit the biological activity of the disclosed 8F4 polypeptide, in particular monoclonal antibodies, natural or synthetic ligands, agonists or antagonists, in particular for preventing or treating diseases which involve the immune system, the use of said 8F4 molecule or cells containing said 8F4 molecule as medicaments, in particular for preventing or treating diseases which involve the immune system, and the use of substances which specifically recognize the disclosed polypeptide, in particular monoclonal antibodies, natural or synthetic ligands, agonists or antagonists, for diagnosing diseases which involve the immune system.

Abstract: This invention provides a composition which comprises an admixture of three compounds, wherein: (a) one compound is an antibody which binds to a CCR5 receptor; (b) one compound retards attachment of HIV-1 to a CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell; and (c) one compound retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate; wherein the relative mass ratio of any two of the compounds in the admixture ranges from about 100:1 to about 1:100, the composition being effective to inhibit HIV-1 infection of the CD4+ cell. This invention also provides a method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with an amount of the composition of the subject invention effective to inhibit HIV-1 infection of the CD4+ cell so as to thereby inhibit HIV-1 infection of the CD4+ cell.

Abstract: A method for determining a soluble human ST2 in a sample conveniently at a high sensitivity and an assay kit are provided. By an immunological method comprising a step for bringing a sample into contact with an immobilized antibody formed by binding to an insoluble support a first anti-human ST2 antibody which binds specifically to a non-denatured human ST2, a step for labelling a first reaction product generated in the previous step by reacting said first reaction product with a second anti-human ST2 antibody which binds specifically to a non-denatured human ST2 by recognizing a site different from the site on ST2 where said first anti-human ST2 antibody binds and which is labelled with a label, and a step for determining the amount of the label on said first reaction product which has been labelled, a soluble human ST2 in a sample is determined. In addition, a recombinant ST2 is employed as a standard to prepare a calibration curve, based on which the ST2 in a sample is quantified.

Abstract: A cell surface molecule that is expressed specifically in thymocytes, lymphocytes activated by ConA-stimulation, and peripheral blood lymphocytes. This molecule is involved in signal transmission of the secondary signal (costimulatory signal) essential for the activation of lymphocytes such as T cells and regulates functions of activated lymphocytes such as activated T cells. Disclosed are an antibody or a portion thereof, which binds to a polypeptide of the cell surface molecule, a polypeptide fragment thereof, or a fusion polypeptide comprising the fragment; a cell secreting the antibody or its portion; a pharmaceutical composition comprising the antibody; and methods of using the compositions for therapeutic, diagnostic and/or experimental purpose.

Abstract: The invention teaches human-compatible monoclonal antibodies which are specific against human CD28 and human T-lymphocytes of several to all sub-groups to activate without occupancy of an antigen receptor of the human T-lymphocytes and thus antigen-non-specifically.

Abstract: Disclosed is a method for treating infection with a pathogen. The method involves administration of: (1) a substance which induces active pathogen replication in a cell latently infected with HIV and (2) an anti-pathogen drug. Also disclosed are methods for expanding CD4+ T cells from peripheral blood mononuclear cells isolated from human subjects in the presence of an antiretroviral drug and for treating HIV infection by infusing the expanded CD4+ cells into HIV-infected patients.

Abstract: The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. Specifically, the present invention relates to expression of hepsin protease. The detected proteases are themselves specifically over-expressed in certain cancers, and the presence of their genetic precursors may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

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: 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: This invention provides a method of isolating CD8+ cells which employs an antibody which specifically binds to CD8 molecules present on the surface of CD8+ cells but does not activate the CD8+ cells once bound. This invention also provides related hybridoma cell lines, monoclonal antibodies, antigenic polypeptides, isolated CD8+ cells, and kits.

Abstract: The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. Specifically, the present invention relates to expression of hepsin protease. The detected proteases are themselves specifically overexpressed in certain cancers, and the presence of their genetic precursors may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

Abstract: Disclosed are methods for the alleviation of symptoms associated with inflammatory disease states, and more particularly to the inhibition of inflammatory disease processes associated with the multiple sclerosis disease, by adminstering to a patient a phamaceutically effective amount of mAb 23F2G or an antibody that competes with mAb 23F2G for binding to LFA-1.

Abstract: The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding human TR11, TR11SV1, and TR11SV2 receptors. TR11, TR11SV1, and TR11SV2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of TR11, TR11SV1, and TR11SV2 receptor activity. The present invention further relates to antibodies that specifically bind TR11, TR11SV1, and/or TR11SV2. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of TR11, TR11SV1, and TR11SV2 receptors. Further provided are therapeutic methods for treating disease states related to aberrant proliferation and differentiation of cells which express the TR11, TR11SV1, and TR11SV2 receptors.

Abstract: The present invention provides T helper cells epitopes and compositions for use in inducing an immune response comprising at least one of these epitopes.

Abstract: The present invention provides methods for enhancing host immunity to a virus and/or a cancer and methods for enhancing the cytotoxic T-cell (CTL) mediated immune responses by providing granzyme B inhibitors to a subject. One objective of the invention is to induce long-term protective immunity to a subject in need thereof This is accomplished by providing granzyme inhibitors to the subject which increase the number of memory-CTLs and thereby prevent or alleviate viral infections and/or treat. Providing granzyme inhibitors is also effective in the prevention of cancers. Some examples of granzyme inhibitors contemplated within the present invention include the endogenous serpins such as SPI6 and PI9, other suicide substrates of granzyme B, granzyme B antibodies, etc. Also provided are methods for expression of nucleic acids encoding granzyme inhibitors in cytotoxic T-lymphocytes (CTLs).

Abstract: The present invention disclosed recombinant anti-VLA-4 antibody molecules, including humanized recombinant anti-VLA-4 antibody molecules. These antibodies are useful in the treatment of specific and non-specific inflammation, including asthma and inflammatory bowel disease. In addition, the humanized recombinant anti-VLA-4 antibodies disclosed can be useful in methods of diagnosing and localizing sites of inflammation.

Abstract: An isolated antibody that specifically binds a peptide coded by a nucleotide sequence coding for a variable region of &agr; chain of an human T lymphocyte receptor, said nucleotide sequence having a nucleotide sequence chosen from any of: V&agr; segments having any one of the sequences SEQ ID Nos. 1 to 11 or J&agr; segments having one of the sequence SEQ ID Nos. 13 or 15 to 19 and hybridomas producing said antibodies.

Abstract: A method of treating a human subject with cancer is disclosed. A pharmaceutical composition is administered to the subject, the pharmaceutical composition comprising human leukocytes and a replication-competent oncolytic virus in suspension in a physiologically acceptable solution. Alternatively the pharmaceutical composition comprises human leukocytes or platelets infected with an oncolytic virus.

Abstract: A monoclonal antibody which binds to baboon and human CD2, and in particular LO-CD2b antibody. The antibody may be employed to prevent and inhibit an immune response in human patients, such as when the immune response is mediated by the activation and proliferation of T-cells or natural killer cells.

Abstract: Disclosed is a method for treating infection with a pathogen. The method involves administration of: (1) a substance which induces active pathogen replication in a cell latently infected with HIV and (2) an anti-pathogen drug. Also disclosed are methods for expanding CD4+ T cells from peripheral blood mononuclear cells isolated from human subjects in the presence of an antiretroviral drug and for treating HIV infection by infusing the expanded CD4+ cells into HIV-infected patients.

Abstract: The present invention relates to a monoclonal antibody against human mononuclear leukocytes which is capable of inhibiting transmigration of human mononuclear leukocytes after their adhesion to vascular endothelial cells, and to a hybridoma producing this antibody, and which can be used for studies to elucidate the mechanism of inflammatory reaction, and the diagnosis and therapy of inflammatory diseases.

Abstract: The present invention provides monoclonal antibodies and binding proteins which specifically bind to the IL-1 receptor. Also provided are methods for detecting IL-1 receptors on cells, and for detecting soluble IL-1 receptors in serum.

Abstract: Disclosed is a method for treating infection with a pathogen. The method involves administration of: (1) a substance which induces active pathogen replication in a cell latently infected with HIV and (2) an anti-pathogen drug. Also disclosed are methods for expanding CD4+ T cells from peripheral blood mononuclear cells isolated from human subjects in the presence of an antiretroviral drug and for treating HIV infection by infusing the expanded CD4+ cells into HIV-infected patients.

Abstract: The present invention relates to methods and compositions for modulating the heterotypic adhesion between E-cadherin expressing cells and T lymphocytes. Monoclonal antibodies which specifically bind to E-cadherin and isolated peptides which mimic the binding function of E-cadherin also are provided. The antibodies and peptides are useful in screening assays to identify pharmaceutical lead compounds which are capable of modulating adhesion between T lymphocytes and E-cadherin expressing cells. Methods and pharmaceutical compositions for modifying the mucosal immune response of a subject also are provided.

Abstract: The present invention relates generally to immunointeractive molecules and their use inter alia in the detection and/or purification of T-cell antigen binding molecules (TABMs). The ability to determine the presence and levels of particular TABMs provides a useful diagnostic procedures for a variety of disease conditions.

Abstract: The subject invention pertains to antibodies that have binding specificity for an antigen that is expressed on a subset of human, hematopoietic mononuclear cells, including a hematopoietic stem cell population, but is not expressed on normal, mature myeloid cells. In one embodiment, a monoclonal antibody, MG1, is provided. This antibody is useful in methods of isolating cell suspensions from human blood and marrow that can be employed in bone marrow transplantation, genetic therapy, and in treating other diseases of the hematopoietic system. Cell suspensions containing MG1+ human hematopoietic cells are also provided, as well as therapeutic methods employing the cell suspensions. The subject invention also pertains to the novel antigen recognized by the subject antibodies.

Abstract: The present invention provides an assay for measuring the immunogenicity of a vaccine, wherein the vaccine contains an epitope having a conformation associated with an immunogenically active form of the vaccine and a fragment having a conformation associated with an immunogenically inactive form of the vaccine, wherein the method includes exposing a sample of the vaccine to a first ligand capable of binding to the epitope in the conformation associated with the immunogenically active form of the vaccine and a second ligand capable of binding to the fragment in the conformation associated with the immunogenically inactive form of the vaccine and measuring the amount of first ligand bound to the vaccine sample and the amount of the second ligand bound to the vaccine sample.

Abstract: The present invention relates to a method of inducing a CD8+ CTL response to a molecule in an individual deficient in CD4+ T cells comprising administering to the individual an hsp or a portion of an ATP binding domain of an hsp joined to the molecule. In one embodiment, the present invention relates to a method of treating HIV in an individual deficient in CD4+T cells comprising administering to the individual an hsp or a portion of an ATP binding domain of an hsp joined to the molecule. Also encompassed by the present invention is a method of inducing a CD4+ independent CTL response in an individual comprising administering to the individual a portion of an ATP binding domain of an hsp joined to the molecule. The present invention also relates to a method of inducing a CD8+ CTL response in an individual comprising administering to the individual a portion of an ATP binding domain of an hsp joined to the molecule.

Abstract: This invention provides a composition which comprises an admixture of three compounds, wherein: (a) one compound is an antibody which binds to a CCR5 receptor; (b) one compound retards attachment of HIV-1 to a CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell; and (c) one compound retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate; wherein the relative mass ratio of any two of the compounds in the admixture ranges from about 100:1 to about 1:100, the composition being effective to inhibit HIV-1 infection of the CD4+ cell.

Abstract: Compositions are provided that comprise antibody against coreceptors for human immunodeficiency virus such as CCR5 and CXCR4. In particular, monoclonal human antibodies against human CCR5 are provided that bind to CCR5 with high affinity and are capable of inhibiting HIV infection at low concentrations. The antibodies can be used as prophylactics or therapeutics to prevent and treat HIV infection, for screening drugs, and for diagnosing diseases or conditions associated with interactions with HIV coreceptors.