Abstract: Compositions and methods effective for eliciting an immune response for inhibiting abnormal or undesirable cell proliferation, particularly endothelial cell proliferation and angiogenesis related to neovascularization and tumor growth are provided. The compositions comprise a naturally occurring or synthetic protein, peptide, or protein fragment containing all or an active portion of a growth factor in a pharmaceutically acceptable carrier. The preferred growth factors comprise basic fibroblast growth factor and vascular endothelial growth factor. The methods involve administering to a human or animal the compositions described herein in a dosage sufficient to elicit an- immune response. The methods are useful for treating diseases and processes mediated by undesired and uncontrolled cell proliferation, such as cancer, particularly where uncontrolled cell proliferation is influenced by the presence of growth factors.

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: The field of the invention is generally related to pharmaceutical agents useful in treating graft-versus-host disease (GVHD) in patients that have received allogenic bone marrow transplants.

Abstract: Disclosed are methods of stimulating in a subject an immune response to an antigen to which the immune response is targeted. This method includes the step of administering to the subject a binding agent which binds a surface receptor of an antigen-presenting cell, in some instances without being blocked substantially by the natural ligand for the surface receptor, and an antigen to which the immune response is targeted, in a physiologically acceptable medium to the subject. Also disclosed are molecular complexes including the binding agent coupled to an antigen.

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: 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: 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: 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: 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: 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: A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of suppressor T cells effective to reduce or inhibit host rejection of the transplant. The suppressor T cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with suppressor T 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 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: A method is provided for reducing the occurrence of fever, headache, nausea and/or vomiting associated with administration of a therapeutic compound to a mammal in need therof, comprising administering to the mammal a first conditioning dose of a non-target cell depleting compound which binds to a cell surface receptor on a target mammalian cell; and administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.

Abstract: The invention provides methods of treating autoimmune and chronic inflammatory conditions by administering agents that hinder the CD30/CD30L interaction, combination treatments, and methods of treating conditions resistant to treatment with TNF&agr; inhibitors by administering agents that inhibit signal transduction by CD30 or IL-1. Included also are treatments involving concurrently administering agents that block the CD30/CD30L interaction and agents that antagonize the IL-4/IL-4R interaction. Additionally provided is an animal model for screening candidate agents for their efficacy in treating conditions that are resistant to treatment with TNF&agr; inhibitors.

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: The present invention concerns the treatment of disorders characterized by the overexpression of ErbB2. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer overexpressing ErbB2 with anti-ErbB2 antibody.

Abstract: The present invention relates to agents that bind CD23 and that can be used in the treatment of inflammatory, autoimmune or allergic diseases.

Abstract: The invention provides methods and compositions relating to two classes of semaphorin receptors, SR1 and SR2. The polypeptides may be produced recombinantly from transformed host cells from the disclosed SR encoding nucleic acids or purified from human cells. The invention provides isolated SR hybridization probes and primers, capable of specifically hybridizing with the disclosed SR genes. SR-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

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: Methods of detecting activated T-cells involve monitoring levels of MUC-1 mucin expression at the protein and/or mRNA level. Compositions for modulating immune function contain compounds that modulate the expression or function of MUC-1. Methods of treating disorders associated an inappropriate state of T-cell activation involve contacting a T-cell with a compound containing an inhibitor of MUC-1 expression or function.

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: A method is provided for reducing the occurrence of fever, headache, nausea and/or vomiting associated with administration of a therapeutic compound to a mammal in need thereof, comprising administering to the mammal a first conditioning dose of a non-target cell depleting compound which binds to a cell surface receptor on a target mammalian cell; and administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.

Abstract: When stimulated through the T cell receptor(TCR)/CD3 complex without requisite costimulation through the CD28/B7 interaction, T cells enter a state of antigen specific unresponsiveness or anergy. This invention is based, at least in part, on the discovery that signaling though a common cytokine receptor &ggr; chain (e.g., interleukin-2 receptor, interleukin-4 receptor, interleukin-7 receptor) prevents the induction of T cell anergy. This &ggr; chain has been found to be associated with a JAK kinase having a molecular weight of about 116 kD (as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis) and signaling through the &ggr; chain induces phosphorylation of the JAK kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor &ggr; chain are disclosed.

Abstract: An antibody is produced, which will bind effectively with the antigen Campath-1, and which has at least one complementarity determining region of rat origin, as identified in FIG. 2, which may be combined with a range of different foreign variable domain framework regions as desired, including framework regions of human origin.

Abstract: The present invention relates to molecules involved in cell-cell interactions in the immune system. In particular, the invention relates to a cell surface protein which contains certain classical cadherin characteristics, but it exhibits an apical distribution pattern on the surface of lymphocytes. The membrane location of this molecule correlates with the contact interface between T and B cells, and antibodies against an extracellular domain of this protein disrupt T cell/B cell interactions.

Abstract: A method of inducing an immune response in a patient is provided. The method involves administration of bispecific molecules capable of recognizing and binding Fc&ggr;RIII and a second antigen. The second antigen may be a cancer antigen, a viral antigen, a fungal antigen, a bacterial antigen or a toxin. The second antigen may or may not be present in the patient at the time the method of the invention is performed.

Abstract: Methods for assessing immunocompetence, cellular or humoral immunity, antigen exposure, or allergic conditions in an individual by accelerating diagnostic particles into a target skin site in the individual are provided.

Abstract: The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM.

Abstract: The present invention provides substantially purified nucleic acid molecules encoding Bax inhibitor protein-1 (BI-1; SEQ ID NO: 1) or Bax inhibitor protein-2 (BI-2; SEQ ID NO: 4), nucleic acid molecules complementary thereto (SEQ ID NO: 2 and SEQ ID NO: 5, respectively), portions of such nucleic acid molecules, vectors containing the nucleic acid molecules, and host cells containing the vectors. The invention also provides methods of using such nucleic acid molecules to identify the presence of a nucleic acid molecule encoding a Bax inhibitor protein in a sample or to increase or decrease the level of expression of a Bax inhibitor protein in a cell. In addition, the invention provides substantially purified BI-1 (SEQ ID NO: 3) and BI-2 (SEQ ID NO: 6) polypeptides, portions of such polypeptides, and antibodies specific for BI-1 or BI-2.

Abstract: Methods for treating and inhibiting disease and symptoms associated with the human immunodeficiency virus (HIV) are provided. The method includes transforming the human immunodeficiency virus (HIV) infection into a nonserious disease through the infusion of monoclonal antibodies directed against particular antigens on anti-self, anti-CD4 cytotoxic T-lymphocytes. The monoclonal antibodies are primarily directed against the alpha or beta chain of LFA-1.

Abstract: The present invention relates to an antibody or functional portion thereof which binds to a mammalian (e.g., human) chemokine receptor 5 protein (CKR-5 or CCR5) or portion of the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR5 with a ligand thereof. Another aspect of the invention relates to a method of inhibiting HIV infection of a cell which expresses a mammalian CCR5 or portion thereof using the antibodies described herein. Also encompassed by the present invention are methods of treating or preventing HIV in a patient.

Abstract: Monoclonal antibodies to the CD25 antigen are characterized by the amino acid sequence of their hypervariable regions. Initially produced in murine form, they may be converted to chimeric or humanized forms, immunoconjugates or antibody fragments (generally described as binding molecules). The products are useful for the prophylaxis or treatment of transplant rejection, paticularly in combination with other antibodies to activated T-cells, for example CD7 antibodies.

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: The present invention is directed to humanized antibodies which bind human gp39 and their use as therapeutic agents. These humanized antibodies are especially useful for treatment of autoimmune diseases.

Abstract: The present invention relates to methods to regulate actin polymerization in T lymphocytes involved in tumorigenesis, inflammatory responses, immune responses, allergic responses and graft rejection responses, kits to perform such assays and methods to identify regulatory reagents that specifically control actin polymerization in T lymphocytes.

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: Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell.

Abstract: The binding specificity of the murine OKT3 has been transferred into a human antibody framework in order to reduce its immunogenicity. These “humanized” anti-CD3 monoclonal antibodies retain, in vitro, all the properties of native anti-CD3 antibodies, including T cell activation which has been correlated, in vivo, with the severe side-effects observed in transplant recipients after the first administration of the mAb.

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: Chimeric antibodies including an Old World monkey portion and a human portion, nucleic acid encoding such antibodies, Old World monkey monoclonal antibodies, and methods for their production and use.

Abstract: The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. The vaccine is administered to the mammal in a manner that induces an immunologically effective response so as to affect the course of the disease. The invention additionally provides specific &bgr;-chain variable regions of the T cell receptor, designated V&bgr;6.2/3, V&bgr;6.5, V&bgr;2, V&bgr;5.1, V&bgr;13 and V&bgr;7, which are central to the pathogenesis of multiple sclerosis (MS).

Abstract: The present invention provides an anti-idiotypic antibody having specific reactivity with an idiotope common to more than one type of anti-HIV-1 antibody, and having no specific reactivity with non-HIV-1 antibodies. The present invention provides methods of diagnosis, monitoring and treatment of HIV-related diseases through the use of this antibody or related compounds.

Abstract: Multivalent, multispecific molecules having at least one specificity for a pathogen and at least one specificity for the HLA class II invariant chain (Ii) are administered to induce clearance of the pathogen. In addition to pathogens, clearance of therapeutic or diagnostic agents, autoantibodies, anti-graft antibodies, and other undesirable compounds may be induced using the multivalent, multispecific molecules.