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: The OX-40 antigen is characterized and claimed together with variants and derivatives thereof. Also described are binding agents for the antigen and the use of these in diagnosis and therapy. Examples of such use include a method for the selective depletion of activated CD4+ T-cells in vivo by using immunotoxins comprising an OX-40 antibody conjugated to a toxic molecule (such as Ricin-A chain). The administration of these specific immunotoxins is used therapeutically to deplete autoimmune reactive CD4+ T-cells which have been implicated in diseases including Multiple Sclerosis, Rheumatoid Arthritis, Sarcoidosis, and Autoimmune Uveitis as well as inflammatory bowel disease and graft-versus-host disease. This type of therapy is also beneficial for eradicating CD4+ T-cell lymphomas and alloreactive CD4+ T-cells involved with a transplantation reaction. The use of the human form of the OX-40 antibody will also help in the early diagnosis of all the diseases mentioned above.

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: 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: The invention concerns an antibody composition which inhibits the binding of interleukin 2 to its high affinity receptor and contains (1) monoclonal antibodies against the &agr; chain of the interleukin 2 receptor and (2) monoclonal antibodies against the &bgr; chain of the interleukin 2 receptor, as well as a pharmaceutical agent which contains the antibody composition according to the present invention.

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: 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: 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 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: The invention provides peptides which are expressed by the env gene of a non-M, non-O HIV-1 virus, in particular a strain designated YBF30. The invention also provides fragments of the peptides that including the V3 loop region and their corresponding nucleotide sequences. The invention further provides kits including diagnostic reagents containing these molecules or immunogenic compositions containing these peptides, as well as methods for screening and typing non-M, non-O HIV-1 viruses and HIV-1 viruses expressing these peptide and/or nucleotide sequences.

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: 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: The present invention relates to antibody composition that are useful in preparing enriched cell preparations such as human hematopoietic progenitor cells and stem cells and non-hematopoietic tumor cells. The invention also relates to kits for carrying out the processes and to the cell preparations prepared by the processes.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells.

Abstract: Recombinant immunotoxin polypeptides are described comprising a CD3-binding domain and a Pseudomonas exotoxin mutant, and in particular, comprising a single chain (sc) Fv as the CD3-binding moiety. A preferred species of the invention comprises scFv(UCHT-1)-PE38. Also disclosed are methods for the preparation of said immunotoxins; functionally equivalent immunotoxins which are intermediates in the preparation of the immunotoxins of the invention, as well as polynucleotide and oligonucleotide intermediates; methods for the prevention and/or treatment of transplant rejection and induction of tolerance, as well as treatment of autoimmune and other immune disorders, using the immunotoxins or pharmaceutically acceptable salts thereof; and pharmaceutical compositions comprising the immunotoxins or pharmaceutically acceptable salts thereof.

Abstract: The present invention is directed to humanized antibodies that specifically bind the protein 4-1BB. The antibodies can be made by grafting of the complementarity determining regions (CDR's) of mouse monoclonal antibody to human 4-1BB to the remaining portions of a human antibody and by making further amino acid replacements. In addition, a pharmaceutical composition that includes the humanized antibody can be made and can be used to treat autoimmune diseases to suppress an immune response. The humanized antibody of the invention has high affinity for human 4-1BB, and exhibits sequence similarity to human antibody. As a result, the pharmaceutical composition of the present invention can be used to treat autoimmune disease and act as an immunosuppressant in humans without much side-effect.

Abstract: This invention provides for an isolated protein specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. This invention also provides for an isolated protein having substantially the same biological activity as the aforementioned isolated protein. In addition, this invention provides for a pharmaceutical composition comprising the isolated protein and a pharmaceutically acceptable carrier.

Abstract: This invention provides a method of inhibiting an allergic response in a subject by inhibiting T cell activation of B cells, wherein said method comprises administering to the subject an antibody capable of binding to a protein which is specifically recognized by monoclonal antibody 5C8 produced by the hybridoma having ATCC Accession No. HB 10916.

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; and an immunosuppressant during transplantation of heterologous cells, tissues or organs, cell therapy, and gene therapy.

Abstract: The present invention provides polypeptides comprising an immunogenic epitope of a M. vaccae protein, polynucleotides encoding such polypeptides, and fusion proteins comprising at least one such polypeptide, together with DNA constructs comprising at least one inventive polynucleotide. Compositions comprising such polypeptides, polynucleotides, fusion proteins and/or DNA constructs may be employed in the treatment of infectious diseases and immune disorders.

Abstract: Methods to treat spinal cord injury using &agr;d monoclonal antibodies are disclosed.

Abstract: The invention concerns retrovirus envelope glycoprotein mutants characterized in that they are glycoproteins capable of specifically binding with chemokine receptors and having an inhibiting activity with respect to a retroviral infection.

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: Disclosed are immunopotentiating agents, and vaccines thereof, which enhance and/or otherwise modify immune responses, and method for their preparation and use in vivo. Immunopotentiating agents can be single agents that act directly, adjuvants added concurrently with the agents, or heteroconjugates wherein the immunopotentiating agent is chemically coupled to the compound against which an immune response is desired. Examples of immunopotentiating agents include monoclonal antibodies, such as anti-CD3, anti-CD2) and anti-CD5 antibodies, and proteins derived from microorganisms (e.g., enterotoxins) which activate T cells. The compounds against which an immune response can be generated, which may be the second component in a heteroconjugate, include compound from abnormal or diseased tissues such as tumors, or infectious agents, such as viruses, bacteria, fungi, protozoal or metozoal parasites, and can be obtained by natural or recombinant means.

Abstract: This invention provides for a method for inhibiting rejection of a transplant organ in a subject which comprises administering to the subject an antibody capable of binding to a protein which is specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. The present invention further provides for a method for inhibiting rejection of a transplant organ in a subject, which comprises administering to the subject a pharmaceutical composition comprising a monoclonal antibody capable of binding to a protein which is specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916. In one embodiment of the invention, the transplant organ is a heart, a kidney or a liver. In another embodiment, the monoclonal antibody is 5c8 produced by the hybridoma having ATCC Accession No. HB 10916.

Abstract: The present invention relates to an efficient method of producing monoclonal antibodies against surface antigens of cells and viruses. The method accommodates for antigens which are present in only relatively small amounts, or antigens of which only very small amounts are available or antigens which easily lose their in vivo conformation. Thus the method according to the invention comprises a series of steps, comprising a step in which B-cells from a mammal injected with surface antigen-comprising material are enriched with respect to the relative number of specific B-cells and a step which comprises a small-scale fusion technique.

Abstract: Use of the blockade of costimulation and hematopoietic stem cells in allograft transplantation.

Abstract: Novel 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: An anti-CD2 monoclonal antibody according to the present invention can be: (1) a chimeric nonclonal antibody CD2 SFv-Ig produced by expression of the construct cloned in recombinant Escherichia coli culture ATCC No. 69277; (2) a monoclonal antibody having complementarity-determining regions identical with those of CD2 SFv-Ig; or (3) a monoclonal antibody competing with CD2 SFv-Ig for binding to CD2 antigen at least about 80% as effectively on a molar basis as CD2 SFv-Ig. Anti-CD2 monoclonal antibodies according to the present invention, as well as other antibodies that can modulate the interactions between T lymphocytes and monocytes, can be used to inhibit the production of HIV-1 by HIV-1-infected T cells in HIV-1-infected patients. In another use, T cells treated in vitro can be reinfused into AIDS patients to increase the proportion of functional non-HIV-1-producing T cells in the patient.

Abstract: A method for the prevention or reversal of transplant rejection, or for therapy for autoimmune diseases, is provided comprising administering compounds such as monoclonal antibodies, that bind specifically to one or more preselected CD45R leukocyte antigens.

Abstract: This invention relates to an antibody which is a modified version of a therapeutic antibody with affinity for a cell-surface antigen, said antibody having reduced affinity for the antigen compared with the therapeutic antibody as a result of a modification or modifications to the antibody molecule, wherein the antibody is capable of inducing immunological tolerance to the therapeutic antibody. The invention further relates to a method of inducing immunological tolerance to a therapeutic antibody comprising administering to a patient an antibody which is a modified version of the therapeutic antibody and which has reduced affinity for the antigen as compared with the therapeutic antibody.

Abstract: Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ.

Abstract: The present invention provides a novel biotherapeutic agent comprising a monoclonal antibody TXU-7, which is specific to the CD7 antigen, conjugated to the pokeweed antiviral protein (PAP). This immunoconjugate was designated TXU-7-PAP. The CD7 antigen is present on the surface of the majority of T-lymphocytes, including those that are the cellular target of the human immunodeficiency virus (HIV). The pokeweed antiviral protein displays broad spectrum antiviral activity toward various plant, animal, and human viruses, including HIV. Prior attempts to generate PAP immunoconjugates with anti-HIV activity have been unsuccessful due to the poor stability of the immunoconjugate in vivo. However, the TXU-7-PAP immunoconjugate described herein displayed potent antiviral activity against HIV-1 and low toxicity in various animal models. Preliminary clinical studies in HIV-1-infected patients demonstrated that the immunoconjugate was well-tolerated and reduced the HIV-1 viral load.

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 relates to an antibody or functional fragment thereof which binds to a mammalian (e.g., human) CC-chemokine receptor 2 (CCR2) or a portion of the receptor and blocks binding of a ligand to the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR2 with a ligand thereof, and to use of the antibodies and fragments in therapeutic, prophylactic and diagnostic methods.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells.

Abstract: Activation of cells bearing CD40 on their cell surface by CD40 ligand is inhibited by contacting the cells with an agent capable of inhibiting interaction between CD40 ligand and the cells, in an amount effective to inhibit activation of the cells. Activation of cells bearing CD40 on their surface by CD40 ligand in a subject is inhibited by administering to the subject an agent capable of inhibiting interaction between CD40 ligand and the cells, in an amount effective to inhibit activation of the cells. Reperfusion injury, in an non-transplant recipient, is a condition associated with CD40 ligand-induced activation of CD40-bearing cells. Therefore, reperfusion injury can be treated by the administration of anti-human CD40L monoclonal antibodies, such as those described herein (e.g. 5c8 mAb).

Abstract: The present invention provides a method of determining the success of a cancer therapy in an individual, comprising the step of measuring the frequency of occurence of an oncofetal antigen-specific subclasses in the individual's peripheral blood. Also provided is a method of determining whether protective immunity against a tumor will develop in an individual, comprising the step of measuring the frequency of oncofetal antigen-specific T cells, tumor cells and macrophages at the site of the tumor which secrete IL-10. Additionally, a method of determining whether an individual having a tumor will go into remission or remain in remission, comprising the step of measuring the frequency of oncofetal antigen-specific Th1 cells, Tc cells and Ts cells, IL-10 and interferon-&ggr; secreting T cells in the peripheral blood.

Abstract: The present invention provides for an isolated nucleic acid molecule encoding a light chain protein of an antibody, wherein the antibody binds specifically to a protein specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession Number HB 10916. The invention also provides for an isolated nucleic acid molecule encoding a heavy chain protein of an antibody, wherein the antibody binds specifically to a protein specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession Number HB 10916. The present invention also provides for a gene transfer vector comprising a nucleic acid molecule, a host vector system comprising the gene transfer vector, and a composition comprising a nucleic acid molecule.

Abstract: Method for the treatment of multiple sclerosis and other T cell mediated autoimmune disorders is described. The method involves administering to a subject a therapeutically effective amount of an antagonist of a receptor on a surface of a T cell which mediates contact dependent helper effector functions, for example, an anti-gp39 antibody.

Abstract: The presence of cytotoxic T-cells to the Rev and/or Tat protein in samples from a subject infected with immunodeficiency virus, particularly HIV in humans, is an indication of a stable disease condition and a favorable prognosis of lack of progression to disease. Immunogenic compositions containing at least one cytotoxic T-cell epitope of the Rev and/or Tat protein of an immunodeficiency virus, particularly HIV, or a vector encoding the T-cell epitope, may be used to prevent infection by disease caused by the immunodeficiency virus, by stimulating, in the host, a specific cytotoxic T-cell response specific for the respective Rev and/or Tat proteins.

Abstract: This invention relates to compositions and methods useful for activating LT-&bgr; receptor signaling, which in turn elicits potent anti-proliferative effects on tumor cells. More particularly, this invention relates to lymphotoxin heteromeric complexes formed between lymphotoxin-&agr; and multiple subunits of lymphotoxin-&bgr;, which induce cytotoxic effects on tumor cells in the presence of lymphotoxin-&bgr; receptor activating agents. Also within the scope of this invention are antibodies directed against the lymphotoxin-&bgr; receptor which act as lymphotoxin-&bgr; receptor activating agents alone or in combination with other lymphotoxin-&bgr; receptor activating agents either in the presence or absence of lymphotoxin-&agr;/&bgr; complexes. A screening method for selecting such antibodies is provided.

Abstract: A method of treating graft-vs-host diseases by administration of bone marrow and an anti-gp39 antibody specific to human gp39 is provided.

Abstract: The present invention relates to an antibody composition which contains antibodies specific for glycophorin A, CD3, CD24, CD16, CD14, and optionally CD45RA, CD38, CD36, CD38, CD56, CD2, CD19, CD66e, CD66b, and/or antibodies specific for antigens expressed on non-hematopoietic tumor cells. A process is also provided for enriching and recovering human hematopoietic progenitor cells and stem cells in a sample containing human hematopoietic differentiated, progenitor, and stem cells, and optionally tumor cells.

Abstract: A pharmaceutical kit and process useful for achieving prolonged immunosuppression and tumor cell elimination, wherein the kit comprises a first antibody having binding specificity for T cells and is capable of eliminating T cells in vivo; and a second antibody, having binding specificity for T cells and is capable of eliminating T cells in vivo, capable of modulating the antigen effect of T cells or both, wherein said first antibody differs from said second antibody in the constant region of its heavy chains and thus belongs to a different animal species, wherein said first antibody and said second antibody are maintained separately in said kit, and wherein in said process said first antibody is first applied once or several times and said second antibody is applied at a different time from said first antibody.

Abstract: Use of the blockade of costimulation and hematopoietic stem cells in allograft transplantation.