Abstract: The invention identifies the B7 antigen as a ligand that is reactive with the CD28 receptor on T cells. The invention further provides methods for using antibodies to B7, or fragments thereof, to regulate CD28 positive T cell response and immune responses mediated by T cells.

Abstract: The invention provides an antibody-toxic moiety conjugates comprising an antibody that specifically recognizes a molecule expressed on the surface of a T cell which is expressed only on T cells and is only expressed transiently on T cells upon T cell activation. Preferably, the T cell molecule is CTLA4. The invention further provides anti-CTLA4 antibodies and humanized forms thereof.

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: Purified genes encoding a T cell surface antigen from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this antigen are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: Methods of enhancing immune responses in which soluble forms of costimulatory molecules, e.g., B7 molecules, are administered to augment immune responses to antigens, e.g., to tumor cells and infectious agents are provided. The subject methods are useful for both prophylactic and therapeutic immunization of subjects.

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.

Abstract: A recombinant antibody or the antibody fragment thereof which specifically reacts with an extracellular domain of human CCR4; a DNA which encodes the recombinant antibody or the antibody fragment thereof; a method for producing the recombinant antibody or the antibody fragment thereof; a method for immunologically detecting CCR4, a method for immunologically detecting a cell which expressed CCR4 on the cell surface, a method for depleting a cell which expresses CCR4 on the cell surface, and a method for inhibiting production of Th2 cytokine, which comprise using the recombinant antibody according or antibody fragment thereof; a therapeutic or diagnostic agent for Th2-mediated immune diseases; and a therapeutic or diagnostic agent for a blood cancer.

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: Methods and compositions for inducing immune suppression are disclosed. The methods involve administering an effective amount of an OX-2 protein or a nucleic acid encoding an OX-2 protein. The methods are useful in preventing graft rejection, fetal loss, autoimmune disease, and allergies. Methods and compositions for preventing immune suppression are also disclosed. The methods involve administering an effective amount of an agent that inhibits OX-2.

Abstract: This invention provides: agents determined to be capable of specifically inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell, but not a T cell-tropic isolate of HIV-1 to a CD4+ cell; and agents determined to be capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4+ cell, but not a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell. This invention also provides: agents capable of specifically inhibiting the fusion of a macrophage tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1; and agents capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 with a CD4+ cell susceptible to infection by a T cell-tropic isolate of HIV-1. The agents include but are not limited to antibodies.

Abstract: The present invention provides machine readable media embedded with the three-dimensional atomic structure coordinates of Synagis Fab, and subsets thereof, and methods of using them.

Abstract: Methods and compositions for regulating immunity are disclosed. For enhancing an immune response, agents that inhibit OX-2 are administered. Such methods are useful in treating cancer. For suppressing an immune response, an OX-2 protein or a nucleic acid encoding an OX-2 protein is administered. Such methods are useful in preventing graft rejection, fetal loss, autoimmune disease, allergies and in inducing tumor cell growth.

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 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 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: 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 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: 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 protein free of cell membranes and other cellular components, said protein being specifically recognized by an antibody that specifically binds an epitope that is specifically bound by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. This invention further provides a protein that is a fragment of a protein specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916, wherein said fragment is free of cell membranes and other cellular components and comprises an epitope that is specifically bound by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. This invention also provides a protein free of cell membranes and other cellular components, said protein consisting essentially of an epitope that is specifically bound by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916.

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: An altered antibody chain is produced in which the CDR's of the variable domain of the chain are derived from a first mammalian species. The framework-encoding regions of DNA encoding the variable domain of the first species are mutated so that the mutated framework-encoding regions encode a framework derived from a second different mammalian species. The or each constant domain of the antibody chain, if present, are also derived from the second mammalian species.

Abstract: Methods of using inhibitors of the CD2/LFA-3 interaction in treating skin conditions characterized by increased T cell activation and abnormal antigen presentation in the dermis and epidermis in mammals, including humans. Such conditions include psoriasis, UV damage, e.g., photoaging, atopic dermatitis, cutaneous T cell lymphoma such as mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.

Abstract: Antibodies against human G-protein chemokine receptor polypeptides, the polypeptides themselves, DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the G-protein chemokine receptor polypeptides, respectively. Also disclosed are diagnostic methods for detecting a mutation in the G-protein chemokine receptor nucleic acid sequences and detecting a level of the soluble form of the receptors in a sample derived from a host.

Abstract: The invention provides recombinant antibody molecules comprising antigen binding regions derived from the heavy and/or light chain variable regions of a donor anti-CD3 antibody, e.g. OKT3, and which have anti-CD3 binding specificity, preferably of affinity similar to that of OKT3. The recombinant antibody is preferably a humanized antibody and may be a chimeric or CDR-grafted antibody. A method is disclosed for preparing CDR-grafted humanized antibodies in which, in addition to the CDR's non-human antibody residues are preferably used at positions 23, 24, 49, 71, 73 and 78 of the heavy chain variable region and at positions 46, 48, 58, and 71 of the light chain variable region. The recombinant, especially the humanized, anti-CD3 antibodies may be used for in vivo therapy or diagnosis.

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: The present invention relates to the identification of macaque antibodies to human B7.1 and B7.2 by screening of phage display libraries or monkey heterohybridomas obtained using B lymphocytes from B7.1 and/or B7.2 immunized monkeys. More specifically, the invention provides four monkey monoclonal antibodies 7B6, 16C10, 7C10 and 20C9 which inhibit the B7:CD28 pathway and thereby function as effective immunosuppressants. The invention further provides the complete DNA and amino acid sequences of the light and heavy chain of three primatized antibodies derived from those monkey monoclonal antibodies which bind B7.1 and possibly B7.2, primatized 7C10, primatized 7B6 and primatized 16C10. These primatized and monkey antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

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

Abstract: Humanized anti-CD11a antibodies and various uses therefor are disclosed. The humanized anti-CD11a antibody may bind specifically to human CD11a I-domain, have an IC50(nM) value of no more than about 1 nM for preventing adhesion of Jurkat cells to normal human epidermal keratinocytes expressing ICAM-1, and/or an IC50 (nM) value of no more than about 1 nM in the mixed lymphocyte response assay.

Abstract: Antibodies that bind to a 40 kDa protein which is expressed on tumors, but is not expressed on normal adult hemopoietic cells are disclosed. Also disclosed are methods for production and the use of such antibodies.

Abstract: Although the mechanism of induction of apoptosis through antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells is well understood, little is known about the fate of the reactive NK cells. Nevertheless, it has been shown that NK cells previously activated by IL-2, but not naive NK cells, died by apoptosis after Fc&ggr;RIIIa crosslinking, or after engagement in cytolytic functions. It is demonstrated that apoptosis of naive NK cells is also observed after stimulation with a rat IgG2b anti CD2 mAb (LO-CD2a/BTI-322) or anti HLAI (LO-HLA-1)mAb. The NK apoptosis is rapid (within minutes), Fas-ligand and mRNA synthesis independent and does not require a cell contact. The intracellular mechanism of NK cell apoptosis is calcium, PKC and PLA2 dependent but calcineurin and P13 kinase independent. We suggest that NK cell apoptosis results from the crosslinking on the same cell surface of CD2 or HLA-I molecules and Fc&ggr;RIIIa that exhibits a high affinity for the rat IgG2b isotype.

Abstract: The invention provides monoclonal and polyclonal antibodies recognising molecules on secretory cells of various tissue targets of autoimmune disease allowing a unifying method of preventing and treating autoimmune diseases and other conditions where hormonal dysregulation, hyperinsulinaemia and insulin resistance are involved. It also provides a method for detecting similar antibodies in human sera or other body fluids which can be used in the development of diagnostic kits. Treatment methods arising from this invention comprise the administration of preparations of the antibodies, their target molecules and vectors containing coding sequences of the antibodies and their target molecules.

Abstract: The invention relates to an antibody or antigen-binding fragment thereof which binds to the CC chemokine receptor GPR-9-6 and blocks the binding of a ligand (e.g., TECK) to the receptor. The invention also relates to a method of identifying agents (molecules, compounds) which can bind to GPR-9-6 and inhibit the binding of a ligand (e.g., TECK) and/or modulate a function of GPR-9-6. The invention further relates to a method of modulating a function of GPR-9-6, and to the use of the antibodies, antigen-binding fragments and agents identified by the method of the invention in research, therapeutic, prophylactic and diagnostic methods.

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: A humanized antibody or antibody fragment having all or part of the CDRs as defined and capable of binding to the human CD18 antigen. The antibody and fragment may be labeled and are useful in a variety of applications, such as in therapy in treating leukocyte mediated conditions such as inhibiting ingress of leukocytes into the lung and other organs and treatment of inflammation. Also provided is a kit for detecting the presence of human CD18 antigen comprising an antibody or fragment of the invention, which is optionally labeled.

Abstract: Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common leukemias in both children and adults. Current treatment strategies are inadequate and often result in patient toxicity and relapse. Accordingly, the need exists for a T-cell-specific immunotoxin with sufficient stability and efficacy to eliminate cell populations associated with various T-cell malignancies. The present invention addresses this concern by providing a biotherapeutic agent (e.g., an immunoconjugate or immunotoxin) comprising a monoclonal antibody (MoAb TXU-7) specific to mammalian T-cell/myeloid antigen CD7 linked to the pokeweed antiviral protein (PAP). The CD7 antigen is expressed on human T-lineage lymphoid cells and leukemic progenitor cells in T-lineage lymphoid malignancies. PAP is a member of the hemitoxin group of toxins and inactivates ribosomes by the removal of a single adenosine from the conserved loop sequence found near the 3′ terminus of all larger RNAs.

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 invention relates to a method of inhibiting stenosis or restenosis in a subject. In one embodiment, an agent which inhibits recruitment and/or adhesion of neutrophils and mononuclear cells to a site of vascular injury is administered to a subject in need thereof. In another embodiment, a first agent which inhibits recruitment and/or adhesion of neutrophils to a site of vascular injury, and a second agent which inhibits recruitment and/or adhesion of mononuclear cells to a site of vascular injury are administered to a subject in need thereof. In particular embodiments, the agents are antibodies or antigen-binding fragments thereof which bind to CD18 or CCR2.

Abstract: The present invention provides a method for determining viral load in a patient infected with human immunodeficiency virus, which is useful in patients where viral loads are not detectable in plasma. The levels of human immunodeficiency virus are measured in CD4−CD8− double negative cells. Furthermore, the invention also provides a kit for determining viral load in a patient infected with human immunodeficiency virus.

Abstract: The invention provides compounds comprising at least one phosphohalohydrin group of the formula: where X is a halogen selected from among I, Br, Cl, R1 is selected from among —CH3 and —CH2—CH3, Cat+ is an organic or inorganic cation, and n is an integer between 2 and 20, processes for the production thereof and uses thereof, in particular therapeutic uses and for activating primate T&ggr;9&dgr;2 lymphocytes.

Abstract: An immunotoxin molecule is described which comprises an antibody specific for human CD40L antigen located on the surface of a human cell, coupled to a toxin molecule or active fragment thereof, wherein the binding of the immunotoxin to the CD40L molecule results in the killing of the CD40L expressing cell. The toxin molecule is especially a type-1 ribosome inactivating protein, or an active fragment thereof. The immunotoxin can be used for the treatment of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus, or T-cell malignancies.

Abstract: Provided are novel DT- and ETA-based immunotoxins and a method of treating an immune system disorder not involving T cell proliferation, comprising administering to the animal an immunotoxin comprising a mutant diphtheria toxin moiety linked to an antibody moiety which routes by the anti-CD3 pathway, or derivatives thereof under conditions such that the disorder is treated. Thus, the present method can treat graft-versus-host disease.

Abstract: The present invention provides monoclonal antibodies which interfere with the interactions between FDCs and B cells, thereby suppressing the proliferation and/or differentiation of B cells in lymphoid follicles. The monoclonal antibodies of the present invention are useful for treating follicular lymphomas, multiple myeloma as well as autoimmune diseases.

Abstract: This invention relates to a method for establishing and using a decision marker by which positive samples can be discriminated from negative samples. The method employs the analysis of multiple samples from confirmed positive and negative samples. A fluorescence channel is selected so that the desired sensitivity and specificity are achieved. A microparticle having this fluorescence channel then is made and is used in conjunction with a fluorescence marker which is specific for the population of interest.

Abstract: This invention provides a method of inhibiting an autoimmune response in an animal suffering from an autoimmune disease selected from the group consisting of psoriasis, Lyme disease and hyper IgE syndrome which comprises administering to the animal, in an amount effective to treat the autoimmune disease, an antibody that binds specifically to a protein specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916.

Abstract: Provided is a method of treating an autoimmune disease in an animal comprising administering to the animal an antibody-DT mutant immunotoxin which routes by the anti-CD3 pathway, or derivatives thereof, under conditions such that the autoimmune disease is treated. In a further embodiment, the invention provides a method of treating T cell leukemias or lymphomas in an animal comprising administering to the animal an antibody-DT mutant immunotoxin which routes by the anti-CD3 pathway, or derivatives thereof, under conditions such that the T cell leukemias or lymphomas are treated.

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: The invention provides a LM609 grafted antibody comprising one or more CDRs having at least one amino acid substitution, where the LM609 grafted antibody has &agr;v&bgr;3 binding activity. Nucleic acids encoding LM609 grafted heavy and light chains are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided. The invention also provides a method of inhibiting a function of &agr;v&bgr;3. The method consists of contacting &agr;v&bgr;3 with a LM609 grafted antibody or functional fragments thereof under conditions which allow binding to &agr;v&bgr;3. Finally, the invention provides for a method of treating an &agr;v&bgr;3-mediated disease. The method consists of administering an effective amount a LM609 grafted antibody or functional fragment thereof under conditions which allow binding to &agr;v&bgr;3.

Abstract: This invention provides methods of treating autoimmune diseases, including those selected from the group consisting of rheumatoid arthritis, Myasthenia gravis, systemic lupus erythematosus, Graves' disease, idiopathic thrombocytopenia purpura, hemolytic anemia and diabetes mellitus with 5C8-specific antibodies.

Abstract: The invention provides novel compounds that enhance dimerization of the subunits of HIV-1 reverse transcriptase having mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). Such compounds inhibit HIV-1 reverse transcriptase activity and as such, inhibit HIV-1, in particular HIV-1 resistant to conventional NNRTIs. The invention provides a method of determining whether a compound enhances formation of a complex between a p66 and p51 subunit polypeptides of HIV-1 reverse transcriptase, in which the p66 subunit has at least one or more mutations associated with resistance of HIV-1 to at least one NNRTI. The invention further provides methods of using a compound that enhances formation of a complex between a p66 subunit polypeptide having at least one mutation associated with resistance of HIV-1 to at least one NNRTI and a p51 subunit of HIV-1 reverse transcriptase.