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 stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of antibody not subjected to prior lyophilization, a buffer maintaining the pH in the range from about 4.5 to about 6.0, a surfactant and a polyol is described, along with uses for such a formulation.

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

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

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

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

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

Abstract: This invention provides anti-HLA-DR antibodies and the methods of use thereof for the treatment of leukemia or lymphomas, or solid tumors such as ovarian cancer or melanoma.

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

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

Abstract: The invention provides immunological reagents (antibodies) capable of binding to plasmacytoid dendritic cells (pDC), to cell lines which express such antibodies and to a process for identifying and purifying plasmacytoid dendriticcells from tissues containing pDC using such antibodies.

Abstract: The invention relates to compositions which bind T cell inhibitory receptor molecules and modulate T cell activity, and methods of using such compositions. Such compositions include biliary glycoprotein binding agents. Methods for modulating killer T cell activities, including cytotoxicity and proliferation also are provided.

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

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

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

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

Abstract: The 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: A c143 monoclonal antibody which is used for detecting a bovine individual having a possibility of onset of bovine leukemia; a monoclonal antibody which is used for detecting a bovine individual having a possibility of onset of bovine leukemia, wherein the monoclonal antibody has the substantially same reactivity as the c143 monoclonal antibody to a bovine MHC Class II DR molecule to which a possibility of onset of bovine leukemia is attributable; and an agent for diagnosing a possibility of onset of bovine leukemia which comprises the aforementioned monoclonal antibody. Bovine individuals having a possibility of onset of bovine leukemia can be conveniently and accurately detected.

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 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: 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 a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of substituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

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: 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 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: 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: 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: Disclosed herein are therapeutic treatment protocols designed for the treatment of B cell lymphoma. These protocols are based upon therapeutic strategies which include the use of administration of immunologically active mouse/human chimeric anti-CD20 antibodies, radiolabeled anti-CD20 antibodies, and cooperative strategies comprising the use of chimeric anti-CD20 antibodies and radiolabeled anti-CD20 antibodies.

Abstract: The present invention provides an isolated nucleic acid encoding KIAA0918, an isolated nucleic acid that hybridizes under high stringency conditions to a nucleic acid that is complementary to a nucleic acid encoding KIAA0918, a purified KIAA0918 protein, a purified protein encoded by a nucleic acid that hybridizes under high stringency conditions to a nucleic acid that is complementary to a nucleic acid encoding KIAA0918, a method of making KIAA0918 protein, an antibody specific for KIAA0918, a method for producing an antibody specific for KIAA0918 protein, a vector comprising a nucleic acid encoding KIAA0918, and a host cell transformed with a vector comprising a nucleic acid encoding KIAA0918. Also provided are methods for detecting the presence of and isolating hematopoietic stem cells in a heterogeneous cell suspension and for assessing gene expression in a tissue sample.

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: A chimeric antibody with human constant region and murine variable region, having specificity to a 35 kDA polypeptide (Bp35(CD20)) expressed on the surface of human B cells, methods of production, and uses.

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: Methods of inhibiting and diagnosing spontaneous abortion in a subject are provided. The subject methods are based, inter alia, on the administration of an agent that inhibits a CD28-C mediated costimulatory signal in a T cell such that spontaneous abortion in the subject is inhibited. The subject methods are also based on the levels of adhesion molecules, inflammatory cytokines, and immune cell surface molecules which are altered in spontaneous abortion.

Abstract: Anti-thrombotic agents containing humanized antibodies which bind to von Willebrand factor.

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: Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.

Abstract: Disclosed is a composition for inhibiting the interactions of B7-1 and B7-2 with their natural ligands. Such compositions comprise an antibody specific for B7-2 and an antibody specific for B7-1, in a pharmaceutically acceptable carrier. The composition may be formulated for either separate or combined administration of the antibody components. The antibodies may be monoclonal antibodies, or humanized antibodies. Preferred antibodies are disclosed.

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: The present invention provides novel immunotoxins and methods of treating neoplastic diseases. These immunotoxins are comprised of a conjugation of an antigen binding region exhibiting binding specificity for the CD33 protein and a cell growth modulator. The immunotoxins of the present invention specifically and selectively kill tumor cells that are characterized by the expression of CD33 antigen. Thus, the novel immunotoxins would be useful in treating human leukemias, both acute and chronic, and other myelodysplastic syndromes.

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.