Abstract: The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that select the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for treatment of cancer or infection.

Abstract: The invention relates to the field of molecular medicine. In particular, it relates to compositions and methods to enhance the clearance of aberrant cells, e.g. cancer cells or virus-infected cells, by the host's immune system. Provided is a composition comprising (i) a therapeutic compound that can trigger a host's immune effector cells against an aberrant cell, such as a therapeutic antibody, and (ii) at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPalpha.

Abstract: The present invention provides compositions, methods, and assays for treating an inflammatory and/or autoimmune disease, and/or transplanted tissue rejection using anti-?? TCR antibodies and antibody fragments. Anti-?? TCR antibodies are antibodies which bind to a ?? TCR. Anti-?? TCR antibodies produced by the hybridoma TOL101 MCB are also provided. Methods for treatment of an inflammatory disease, an autoimmune disease and for tissue transplant rejection using therapeutic dosing regimen of anti-?? TCR antibodies and antibody fragments and for upregulating the numbers of Treg T-cells are also provided. The present invention also provides methods of treating inflammatory and/or autoimmune disease, and/or transplanted tissue rejection using a therapeutic amount of ex vivo expanded regulatory T-cells.

Abstract: We provide an antibody capable of binding to an intracellular PRL-1 or PRL-3 polypeptide, in which the antibody is capable of binding to an epitope bound by antibody 269, antibody 223 or antibody 318. Such anti-PRL antibodies may be capable of binding to intracellular PRL-1 or PRL-3. They may be suitable for use as therapies against cancer or metastasis thereof, or in clinical diagnosis to identify PRL-3 or PRL-1 positive patients.

Abstract: The present invention relates to methods for reducing or eliminating the non-specific release of a cytokine associated with a disease comprising administering at least one glucocorticoid and an immunostimulating antibody. Additionally, the present invention relates to a pharmaceutical composition that contains at least one immunostimulating antibody and at least one glucocorticoid.

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: The present invention relates to molecules comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc?RIIIA and/or Fc?RIIA with a greater affinity relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are useful in preventing, treating, or ameliorating symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function mediated by Fc?R is desired, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Abstract: The present invention relates to compositions containing antibodies for treating CD5+ HLA-DR+ B OR T cell related diseases such as B or T cell malignances (leukaemia and lymphoma), autoimmune diseases and T cell related diseases as transplantation and graft rejection.

Abstract: Molecules that interact with the NKT cell antigen receptor and its counterpart antigen presenting molecule, but which inhibit the NKT cell immune function, are administered to a patient. Conditions of particular interest include the treatment of systemic lupus erythematosus (SLE), cancer, atherosclerosis, and allergic disease. In some embodiment of the invention, the inhibitory agent is an anergizing glycolipid, for example ?-galactosylceramide. Pharmaceutical formulations of such glycolipids are provided, and find use in the treatment of diseases involving undesirable NKT cell activation.

Abstract: Methods and therapeutic agents are disclosed for treating neurodegenerative disorders by depletion of CD8 positive T cells by using antibodies, FAb fragments of antibodies or similar agents that sequester, neutralize or deplete the CD8+ cytotoxic T cells.

Abstract: The present invention provides methods of treating, preventing or ameliorating the symptoms of T cell-mediated immunological diseases, particularly autoimmune diseases, through the use of anti-CD3 antibodies. In particular, the methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor/alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the invention provides for modification of the anti-CD3 antibodies such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-CD3 antibodies.

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: This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.

Abstract: Disclosed are an anti-human TIM-3 antibody having high ADCC activity or antibody fragment thereof by screening a monoclonal antibody or antibody fragment thereof which binds to the amino acid sequence of the extracellular region of TIM-3 or its three-dimensional structure and exhibits ADCC activity; a hybridoma which produces the antibody; a DNA encoding the antibody; a vector comprising the DNA; a transformant which is obtainable by introducing the vector; a method for producing the antibody or the antibody fragment thereof which comprises using the hybridoma or the transformant; and a therapeutic agent and a diagnostic agent comprising the antibody or the antibody fragment thereof as an active ingredient.

Abstract: The present invention provides peptides, and fragments thereof, and antibodies, or fragments thereof comprising the same, wherein the peptide comprises at least one amino acid substitution compared to wild type 5c8 antibody. The present invention also provides compositions and methods of treating CD154-related diseases or disorders in a subject.

Abstract: Disclosed are CD70 binding agents, such as anti-CD70 antibodies and derivatives, that induce a cytotoxic, cytostatic or immunosuppressive without conjugation to a therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody or derivative. Also disclosed are methods for the treatment and prevention of CD70-expressing cancers and immunological disorders comprising administering to a subject the CD70-binding agent.

Abstract: Methods are provided for treating metastatic cancer in patients having metastatic cancer or for preventing metastasis in cancer patients at risk for metastasis comprising administering to the patient an antibody to B7x, or an active antibody fragment that binds B7x, in an amount effective to treat or prevent metastasis.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is an adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: The present invention relates to humanized immunoglobulins, mouse monoclonal antibodies and chimeric antibodies that have binding specificity for human CD52. The present invention further relates to a humanized immunoglobulin light chain and a humanized immunoglobulin heavy chain. The invention also relates to isolated nucleic acids, recombinant vectors and host cells that comprise a sequence which encodes a humanized immunoglobulin or immunoglobulin light chain or heavy chain, and to a method of preparing a humanized immunoglobulin. The humanized immunoglobulins can be used in therapeutic applications to treat, for example, autoimmune disease, cancer, non-Hodgkin's lymphoma, multiple sclerosis and chronic lymphocytic leukemia.

Abstract: Immunostimulatory methods and systems for treating or preventing atherosclerosis and/or a condition associated thereto in an individual.

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: The invention relates to the use of a CD28-specific superagonistic monoclonal antibody (mAb) or of a mimicry compound hereto for making a pharmaceutical composition for the induction and/or multiplication of regulatory T cells.

Abstract: The present invention describes humanized antibodies that target CD40, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an Fc?R or alters effector function as compared to the parent antibody. Also disclosed are methods of using the antibodies of the invention.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Abstract: The present invention relates to pharmaceutical compositions comprising a 2-amino-2-[2-(4-C2-20-alkyl-phenypethyl]propane-1,3-diol compound or a pharmaceutically acceptable salt thereof, and to the use thereof for treating, preventing or delaying the progression of multiple sclerosis in a paediatric patient or a patient suffering from a specific condition.

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 and/or CD40L 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: Antibodies that interact with interleukin-1 receptor type 1 (IL-1R1) are described. Methods of treating IL-1 mediated diseases by administering a pharmaceutically effective amount of antibodies to IL-1R1 are described. Methods of detecting the amount of IL-1R1 in a sample using antibodies to IL-1R1 are described.

Abstract: A composite polypeptide, said composite polypeptide comprising a desired polypeptide and an expression enhancing domain (“EED”), said EED comprising first and second cysteine amino acid residues Cys1 and Cys2, respectively, Cys1 being located closer to the N-terminus of the composite polypeptide molecule than Cys2, wherein Cys1 and Cys2 are separated by a polypeptide linker, said linker—being free of cysteine and proline;—defining a length sufficient to allow Cys1 and Cys2 to engage in an intramolecular disulfide bond with one another; and—having a flexible polypeptide conformation essentially free of secondary polypeptide structure in aqueous solution, wherein at least one of Cys1 and Cys2 is derivatized with a derivatization moiety.

Abstract: The present invention provides novel antibodies and functional fragments thereof specific for CD38, and methods of using the same for the treatment of diseases associated with CD38 expression, including hematological malignancies such as multiple myeloma.

Abstract: The invention pertains to the generation and utility of antibodies that can bind effectively to C?mX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The C?mX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mIgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP (SEQ ID NO:1) peptide at the C-terminal of C?mX, have now been found to bind poorly to mIgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL (SEQ ID NO:2) and HSGQQQGLPRAAGGSVPHPR (SEQ ID NO:3), of C?mX can bind effectively to mIgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. In particular, the invention describes a gene known in the art, alternatively, as ST2, T1 and Fit-1, and referred to herein as the 103 gene. The 103 gene is disclosed herein to be differentially expressed in TH2 cells and not in TH1 cells. Further, the 103 gene product is demonstrated herein to be an important modulator of TH2 and TH2-like immune response both in vitro and in vivo. Thus, the 103 gene, its gene products and antibodies that specifically bind thereto can be used diagnostically or as targets for therapeutic intervention in the treatment of a variety of immune disorders. In this regard, the invention provides methods for the identification and therapeutic use of compounds for treatments of immune disorders, especially TH cell subpopulation-related disorders and including TH2 and TH2-like disorders (i.e.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.

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: 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: 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: The present invention relates, e.g., to an isolated peptide comprising a sequence of contiguous amino acids that is at least about 60% identical (e.g., at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 100% identical) to the sequence E-W-Q-K-E-G-L-V-T-L-W-L (SEQ ID NO:1), or an active variant of an isolated peptide comprising SEQ ID NO:1. Neutralizing antibodies generated by, or specific for, such peptides are also described, in particular antibodies which are specific for the HIV co-receptor, CCR5, and which inhibit infection of a host cell by HIV. Neutralizing single strand and complete human monoclonal antibodies against CCR5 are described. Methods of using such peptides or antibodies, for inhibiting infection by HIV, are also described.

Abstract: The present invention relates to diagnostic and therapeutic methods in the field of malignant disorders. Most particularly, the invention provides methods of determining the invasivity of malignant disorders and methods for reducing the invasivity of malignant disorders including the prevention or treatment of cancer cell invasion.

Abstract: Prevention of autoimmune disease and induction of transplantation tolerance in a recipient can be achieved by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI)-conditioning of the recipient. The toxicity of radiation and potential for graft versus host disease (GVHD) prevents its clinical application. Donor CD8+ T cells play a critical role in facilitation of engraftment, but also contribute to induction of GVHD in TBI-conditioned recipients. It is disclosed herein that high doses of donor CD8+ T cells in combination with donor bone marrow (BM) cells induces mixed chimerism without GVHD in recipients conditioned with anti-CD3 mAb. These chimeric recipients display donor specific tolerance and reversal of insulitis. These results establish that donor CD8+ T cell-mediated facilitation of engraftment can be separated from GVHD in non-irradiated recipients.

Abstract: Disclosed are pharmaceutical combinations comprising at least one S1P receptor agonist, as well as a method for treating demyelinating diseases, e.g. multiple sclerosis or disorders associated therewith or Guillain-Barré syndrome, comprising co-administration, e.g. concomitantly or in sequence, of a therapeutically effective amount of a) an S1P receptor agonist, and b) at least one co-agent shown to have clinical activity against at least one symptom of a demyelinating disease.

Abstract: The invention encompasses compounds having formula I and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases are therapeutically useful.

Abstract: The invention provides methods of treatment using humanized immunoglobulins that specifically bind to alpha-4 integrin. The methods are useful for treatment of asthma, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, transplant rejection, graft versus host disease, tumor metastasis, nephritis, atopic dermatitis, psoriasis, myocardial ischemia, and acute leukocyte mediated lung injury.

Abstract: The invention relates to factor D inhibitors, which bind to factor D and block the functional activity of factor D in complement activation. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab?)2 and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. A monoclonal antibody which bound to factor D and blocked its ability to activate complement was generated and designated 166-32. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number HB-12476.

Abstract: The invention relates to transgenic non-human animals capable of producing high affinity human sequence antibodies. The invention is also directed to human sequence antibodies specific for human antigens , such as, human CD4. The invention also is directed to methods for producing human sequence antibodies.

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: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide 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 humanized anti-human Factor D monoclonal antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

Abstract: Disclosed are methods of treating subjects having cancers including administering an effective amount of an early activation molecule agonist, antagonist or depletor, to the subject. Human monoclonal antibodies specific to the early activation molecules, and methods of use, are also disclosed.

Abstract: The present invention features a novel combination therapy useful in the treatment of autoimmune disease that increases or maintains the number of functional cells of a predetermined type in a mammal by killing or inactivating autoimmune cells and re-educating the host immune system.

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.