Abstract: High affinity antibody antagonists of human interleukin-13 receptor alpha 1 are disclosed. The antibody molecules are effective in the inhibition of IL-13R?1-mediated activities and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with hIL-13R?1 activity. The present invention also discloses nucleic acid encoding said antibody molecules, vectors, host cells, and compositions comprising the antibody molecules. Methods of using the antibody molecules for inhibiting or antagonizing IL-13R?1-mediated activities are also disclosed.

Abstract: The present invention discloses compositions having particles comprising, inorganic element; one or more active ingredient and optionally a release rate modulating agent, suitable for the delivery of active ingredients to human and animal tissues. The particles are nanoparticles or microparticles or mixtures thereof, made preferably by sol-gel method. The compositions are useful for application to the topical or mucosal surfaces preferably in the form of creams, gels, lotions, dry powders, spray, foam and other suitable forms.

Abstract: Compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as autoimmune diseases, transplant rejection, and allergic diseases.

Abstract: A method of inhibiting Th1 immune response in a subject in need of such treatment which comprises administering to the subject effective amounts for inhibiting Th1 immune response of an anti-CD3 monoclonal antibody and IL-5 or an analogue or mimetic thereof.

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

Abstract: Disclosed herein are methods for humanizing antibodies based on selecting variable region framework sequences from human antibody genes by comparing canonical CDR structure types for CDR sequences of the variable region of a non-human antibody to canonical CDR structure types for corresponding CDRs from a library of human antibody sequences, preferably germline antibody gene segments. Human antibody variable regions having similar canonical CDR structure types to the non-human CDRs form a subset of member human antibody sequences from which to select human framework sequences. The subset members may be further ranked by amino acid similarity between the human and the non-human CDR sequences.

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 present invention relates to the field of immunology and hyperproliferative diseases. More specifically, the present invention relates to a method of detecting and monitoring therapeutic antibody:antigen complex, soluble antigen and soluble therapeutic antibody, wherein a patient has undergone at least one course of immunotherapy. Yet further, levels of therapeutic antibody:antigen complexes, soluble antigens or soluble therapeutic antibodies may be measured and used to stage or monitor a hyperproliferative disease.

Abstract: The invention concerns novel DNA and amino acid sequences of monoclonal antibodies (mAbs) raised against lymphoblastoid cells and peptides to which the mAbs bind to. The invention also concerns diagnostic assays using said antibodies or peptides for detecting individuals with a high probability of having a malignant disease and, at times, for detecting an individual having a specific malignant disease. The invention further concerns pharmaceutical compositions comprising the mAbs or peptides of the invention for use in the treatment of various malignant diseases as well as methods for the treatment of malignant diseases using the mAbs or peptides of the invention.

Abstract: PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.

Abstract: Pharmaceutical composition including a soluble form of CD160 for treating an inflammatory condition involving an undesired immune response, such as tissue graft or organ rejection, and autoimmune diseases; in vitro method for screening an individual for the presence of an inflammatory condition such as infectious and autoimmune diseases, tissue graft and organ rejection, or the presence of a tumor or activated endothelial cells, or for monitoring therapy of an inflammatory condition such as an autoimmune disorder or a tissue or organ rejection, or a tumor during chemotherapy including treatment with an anti-angiogenic substance or antibody.

Abstract: Compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as autoimmune diseases, transplant rejection, and allergic diseases.

Abstract: The invention features methods for increasing or maintaining the number of functional cells of a predetermined type, for example, insulin producing cells of the pancreas, blood cells, spleen cells, brain cells, heart cells, vascular tissue cells, cells of the bile duct, or skin cells, in a mammal (e.g., a human patient) that has injured or damaged cells of the predetermined type.

Abstract: Immunoglobulin chains or antibodies having light or heavy chain complementarity determining regions of antibodies that bind to P-Selectin Glycoprotein Ligand-1. Also disclosed are methods of inducing death of an activated T-cell and of modulating a T cell-mediated immune response in a subject.

Abstract: Although results from preclinical studies in animal models have proven the concept for use of anti-CTLA-4 antibodies in cancer immunotherapy, two major obstacles have hindered their successful application for human cancer therapy. First, the lack of in vitro correlates of the anti-tumor effect of the antibodies makes it difficult to screen for the most efficacious antibody by in vitro analysis. Second, significant autoimmune side-effects have been observed In a recent clinical trial. In order to address these two issues, we have generated human CTLA-4 gene knock-in mice and used them to compare a panel of anti-human CTLA-4 antibodies for their ability to induce tumor rejection and autoimmunity. Surprisingly, while all antibodies induced protection against cancer and demonstrated some autoimmune side effects, the antibody that induced the strongest protection also induced the least autoimmune side effects. These results demonstrate that autoimmune disease does not quantitatively correlate with cancer immunity.

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: 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 provides to methods of preventing, treating or ameliorating an autoimmune or inflammatory disorder or one or more symptoms thereof utilizing combinatorial therapy. In particular, the present invention provides methods of preventing, treating, or ameliorating an autoimmune or inflammatory disorder or one or more symptoms thereof comprising administering to a subject in need thereof one or more CD2 antagonists and at least one other prophylactic or therapeutic agent. The present invention also provides compositions and articles of manufacture for use in preventing, treating or ameliorating one or more symptoms associated with an autoimmune or inflammatory disorder.

Abstract: The invention relates to antibody polypeptides that monovalently bind CD40L. Antibody polypeptides that are monovalent for binding of CD40L can inhibit CD40L activity while avoiding potential undesirable effects that can occur with antibodies capable of divalent or multivalent binding of CD40L. In one aspect, a monovalent anti-CD40L antibody polypeptide consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD40L, preferably without substantially agonizing CD40 activity. In another aspect, the monovalent anti-CD40L antibody polypeptide is a human antibody polypeptide. The invention further encompasses methods of antagonizing CD40/CD40L interactions in an individual and methods of treating diseases or disorders involving CD40/CD40L interactions, the methods involving administering a monovalent anti-CD40L antibody polypeptide to the individual.

Abstract: An antibody against AILIM (alternatively called JTT-1 antigen, JTT-2 antigen, ICOS and 8F4) was found to have a significant therapeutic effect on arthrosis, for example, rheumatoid arthritis and osteoarthritis, graft versus host disease, graft immune rejection, inflammation (hepatitis and inflammatory bowel diseases), diseased condition accompanied by the excessive production of an antibody against a foreign antigen triggered by immunological sensitization by the antigen.

Abstract: The present invention provides for novel compositions of anti-CTLA-4 antibodies comprising a chelating agent. Also provided are method of treating diseases and conditions with novel compositions of CTLA-4 antibodies, including various neoplasia conditions.

Abstract: Methods and compositions are described for targeting therapeutic and diagnostic molecules to particular types of cells using targeting antibodies or other targeting moeities.

Abstract: The instant invention provides compositions and methods for downmodulation of immune responses, e.g., autoimmune responses. For example, methods of downmodulating an immune response using agents that specifically block CD28-mediated signaling are provided. The subject methods are useful for both prophylactic and therapeutic downmodulation of immune responses.

Abstract: GM-CSF administered before immunization exerted a sustained suppressive effect against the induction of myasthenia gravis (MG). This suppression was associated with lowered serum autoantibody levels, reduced T cell proliferative responses to AChR, and an expansion in the population of FoxP3+ regulatory T cells. Manipulating DCs to expand regulatory T cells is useful for the control of autoimmune diseases such as myasthenia gravis MG.

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

Abstract: Small animal models for assessing immunomodulatory effects of compounds are provided.

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 is based upon the surprising discovery that exposure of a non-resistant HIV to a first entry inhibitor, such as an anti-CD4 antibody or a co-receptor inhibitor, which like all current HIV drugs selects for mutations that result in a resistant HIV, surprisingly results in HIV viruses much more susceptible to neutralization by a second entry inhibitor, such as soluble CD4 (sCD4) or an HIV gp41 inhibitor. Therefore, the present invention provides methods and compositions for inhibiting HIV-1 infection in a subject that overcomes the problem of drug resistance.

Abstract: Described are methods of treating viral disease using compounds that block inhibitory NK cell receptors, thereby reducing their inhibition of NK cell cytotoxicity in killing infected target cells. In one embodiment, the compound is an antibody binding, for example, one or more of the human KIR2DL1, KIR2DL2, and KIR2DL3 receptors. In another embodiment, the method further comprises administering a therapeutic antibody or fusion protein which binds an antigen expressed on cells infected with the virus.

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: Methods of suppressing a humoral immune response to a thymus-dependent (TD) antigen are disclosed. The methods involve administering to a subject a TD antigen with an antagonist of a molecule which mediates contact-dependent helper effector functions. In a preferred embodiment, the antagonist is an antagonist of gp39. Primary and secondary humoral immune responses can be suppressed and suppression is prolonged.

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

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: The present invention provides method of treatment using human sequence antibodies against human CTLA-4. In particular, methods of treating cancer are provided.

Abstract: A humanized antibody derived from mouse monoclonal anti-CD4 antibody B-F5 is able to activate CD25+CD4+ regulatory T cells and is useful for preparing immunosuppressive compositions.

Abstract: A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect.

Abstract: The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease.

Abstract: Graft rejection is a serious problem associated with tissue or organ transplantation (e.g., allotransplantation or xenotransplantation), performed to treat various organ failures (e.g., liver, heart, lung, kidney, or pancreas). Described are pharmaceutical compositions for suppressing, treating, or preventing graft rejection comprising a substance having an activity to modulate signal transduction mediated by AILIM, and a pharmaceutically acceptable carrier.

Abstract: The invention is directed to a new method for the treatment of new onset Type I diabetes in mammals or for the treatment of pre-Type I diabetic mammals where the method comprises administering (a) anti-T cell therapy to the mammal and administering (b) an autoantigen and optional mucosal antigen composition, wherein (a) and (b) are administered concurrently or sequentially Exemplified is a treatment using a mixture of anti-CD3 antibodies, a glutamic acid decarboxylase (GAD) autoantigen, and an immunoregulatory cytokine Canme GAD sequences are also disclosed.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity to ?v?3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided. The invention also provides a method of inhibiting a function of ?v?3. The method consists of contacting ?v?3 with Vitaxin or a LM609 grafted antibody or functional fragments thereof under conditions which allow binding to ?v?3.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity ?v?3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. The invention additionally provides a high affinity LM609 grafted antibody comprising one or more CDRs having at least one amino acid substitution, where the ?v?3 binding activity of the high affinity LM609 grafted antibody is enhanced. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided.

Abstract: TACI receptor antibodies are provided. The TACI antibodies may be included in pharmaceutical compositions, articles of manufacture, or kits. Methods of treatment and diagnosis using the TACI antibodies are also provided.

Abstract: The present invention relates to methods for the treatment and diagnosis of immune related diseases, including those mediated by cytokines released primarily either Th1 or Th2 cells in response to antigenic stimulation. The present invention further relates to methods for biasing the differentiation of T-cells in either the Th1 subtype or the Th2 subtype, based on the relative expression levels of the gene TCCR, and its agonists or antagonists. The present invention further relates to a method of diagnosing Th1- and Th2-mediated diseases.

Abstract: Isolated human monoclonal antibodies which bind to CD30 (e.g., human CD30) are disclosed. The human antibodies can be produced in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are derivatives of the human antibodies (e.g., bispecific antibodies and immunoconjugates), pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: The invention relates to methods of inducing an anti-tumor immunity and/or inducing an immune responses to p53 in mammals. The methods comprise administering to a mammal an effective amount of at least one immunogen selected from the group consisting of: (i) a peptide based on a CDR of the heavy or light chain of an anti-p53 mAb, which peptide is capable of eliciting antibodies to p53; and (ii) a DNA molecule coding for the variable (V) region of an anti-p53 mAb in a suitable gene delivery vehicle. Preferably the immunogen is administered in the form of a pharmaceutical composition. Preferably the peptide is 7 to 30 amino acid residues in length and contains a sequence of the CDR2 or CDR3 of the heavy chain, or of the CDR3 of the light chain of an anti-p53 mAb.

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

Abstract: 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: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

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