Abstract: Provided is a chimeric antigen receptor-modified immune effector cell carrying a procedural death ligand 1 (PD-L1) blocking agent. Also provided is a method for secreting and expressing a PD-L1 blocking agent using the immune effector cell as a carrier to improve the anti-tumour effect of the chimeric antigen receptor-modified immune effector cell.

Abstract: The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.

Abstract: Improved anti-CD154 antibodies are provided herein which have ablated FcR binding and/or complement binding/activation. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.

Abstract: An object is to provide a signal peptide that can secrete a heterologous polypeptide with high efficiency outside the bacterial cell in a bacterium of the genus Bifidobacterium, an expression cassette that can secrete a heterologous polypeptide with high efficiency outside the bacterial cell, a heterologous polypeptide expression vector, a bacterium of the genus Bifidobacterium capable of secreting a heterologous polypeptide. Means for attaining the object is a bacterium of the genus Bifidobacterium transformed by a vector having an expression cassette sequentially comprising a promoter DNA functioning in a bacterium of the genus Bifidobacterium, a DNA encoding the secretory signal peptide, a DNA encoding a scFv antibody having an antitumor activity, and a terminator DNA functioning in the bacterium of the genus Bifidobacterium; and capable of secreting the scFv antibody with high efficiency outside the bacterial cell.

Abstract: Human antibodies, preferably recombinant human antibodies, both humanized and chimeric, which specifically bind to human OX40 are disclosed. Preferred antibodies have high affinity for OX40 receptor and activate the receptor in vitro and in vivo. The antibody can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, are useful for modulating receptor activity, e.g., in a human subject suffering from a disorder in which OX40 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies are provided, and methods of synthesizing the recombinant human antibodies, are also provided.

Abstract: The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.

Abstract: Compositions are provided, which can be used as frameworks for the creation of very stable and soluble single-chain Fv antibody fragments. These frameworks have been selected for intracellular performance and are thus ideally suited for the creation of scFv antibody fragments or scFv antibody libraries for applications where stability and solubility are limiting factors for the performance of antibody fragments, such as in the reducing environment of a cell. Such frameworks can also be used to identify highly conserved residues and consensus sequences which demonstrate enhanced solubility and stability.

Abstract: Improved anti-CD154 antibodies are provided herein which have ablated FcR binding and/or complement binding/activation. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.

Abstract: The present invention relates to a peptide or peptide complex binding to ?2 integrin, to one or more nucleic acid(s) coding for the peptide or peptide complex, a recombinant cell producing the peptide or peptide complex, a method for producing the peptide or peptide complex, a pharmaceutical composition comprising the peptide or peptide complex or the nucleic acid(s) for use as a medicament, a method for detecting ?2 integrin and a screening method.

Abstract: Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single VH or VK domain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen.

Abstract: Disclosed is a human murine chimeric antibody targeting CD138 which substantially retains the antigen binding region of its murine counterpart. The engineered antibody displays improved binding affinities to the antigen and/or more homogenous binding to target cells relative to its murine counterpart. A constant region of the immunoglobulin heavy chain is preferably an IgG4 isotype constant region.

Abstract: A method is provided for preventing rejection by an immune system of a recipient subject of a tissue transplanted from a donor subject into the recipient subject without the need for long-term administration of non-specific immunosuppressive drugs.

Abstract: An HLA-binding peptide binding to an HLA-A type molecule is provided that includes one or more types of amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 52, and not less than 8 and not more than 11 amino acid residues. All of these amino acid sequences are amino acid sequences predicted to bind to a human HLA-A molecule using a prediction program employing an active learning experiment method shown in FIG. 1.

Abstract: The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), 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 particularly useful in preventing, treating, or ameliorating one or more 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 (e.g., ADCC) mediated by Fc?R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Abstract: The present disclosure provides isolated binding molecules that bind to the human OX40R, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.

Abstract: Improved anti-CD154 antibodies are provided herein which have ablated FcR binding and/or complement binding/activation. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.

Abstract: The use of trifunctional bispecific antibodies for the preparation of a pharmaceutical composition for the prophylaxis and treatment of tumor diseases is provided. Trifunctional bispecific antibodies bind to tumor-associated antigens including Her2/neu, CD20, EpCAM, G250, proteoglycans, GD3. GD2, MHC II, EGF-R and CEA expressed on tumor cells at low to medium expression levels. Also provided are methods for the treatment or prophylaxis of tumor diseases by administering a pharmaceutically effective amount of a trifunctional bispecific antibody to a patient in need thereof.

Abstract: Methods, uses, agents and compositions useful for the diagnosis, prevention and/or treatment of inflammatory conditions, such as neuroinflammatory conditions such as multiple sclerosis, and for the identification and selection of inflammatory cytokine-secreting T cell or a precursor thereof, based on the expression and/or modulation of melanoma cell adhesion molecule (MCAM) are disclosed.

Abstract: Mammals with cancer are treated with an antibody which specifically binds to CD223 protein and inhibits negative T cell regulatory function of CD223. The mammal may be a human. The antibody may be a monoclonal antibody. The amount of the antibody administered may be sufficient to enhance an immune T cell response to the cancer.

Abstract: Human antibodies, preferably recombinant human antibodies, both humanized and chimeric, which specifically bind to human OX40 are disclosed. Preferred antibodies have high affinity for OX40 receptor and activate the receptor in vitro and in vivo. The antibody can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, are useful for modulating receptor activity, e.g., in a human subject suffering from a disorder in which OX40 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies are provided, and methods of synthesizing the recombinant human antibodies, are also provided.

Abstract: Methods of enhancing the efficacy of antibody-directed cellular cytotoxicity (ADCC) for therapy directed to killing of tumor cells are disclosed. Cancer specific cell surface antigens are bound by monoclonal antibodies, thereby stimulating a cytotoxic T cell response characterized by an upregulation of cell surface expression of costimulatory molecules on the T cell. The ADCC response is augmented by the subsequent administration of a second antibody that is an agonist of the costimulatory molecule.

Abstract: A humanized agonistic antibody which binds human PD-1 comprising a heavy chain wherein the variable domain of the heavy chain comprises the sequence given in SEQ ID NO:1 for CDR-H1, the sequence given in SEQ ID NO: 2 for CDR-H2 and the sequence given in SEQ ID NO: 3 for CDR-H3 and the heavy chain framework region is derived from human sub-group sequence VH4 3-1 4-30.4+JH4 (SEQ ID NO: 33). The disclosure also extends to therapeutic uses of the antibody molecules, compositions and methods for producing said antibody molecules.

Abstract: The invention provides novel polypeptides useful for co-stimulating T cells, isolated nucleic acid molecules encoding them, vectors containing the nucleic acid molecules, and cells containing the vectors. Also included are methods of making and using these co-stimulatory polypeptides.

Abstract: The present invention provides a specific binding molecule which binds to Annexin-1 (Anx-A1) for use in the treatment of T cell-mediated disease.

Abstract: The present invention comprises a humanized monoclonal antibody that binds to the chemokine receptor CCR4. This antibody is derived from Mab 1567 and recognizes the same epitope. Binding of the invented antibody to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.

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: The present invention relates to a substance specific to human PD-1 comprising a part that recognizes human PD-1, a part that recognizes a membrane protein in cell membrane of human PD-1-expressing cells, and linkers. Since the substance specific to human PD-1 selectively can recognize human PD-1 and a membrane protein on cell membrane of human PD-1-expressing cells and can transmit inhibitory signal of human PD-1, it is useful for therapy and/or prevention of diseases caused by immunopathy.

Abstract: Method of identifying a modulator of CD28 comprising comparing a structural model of a candidate modulator with a structural model of CD28 to thereby determine whether the modulator will bind to CD28, wherein the structural model is derived from, or comprises, structural coordinates of a crystal of: (i) CD28, (ii) a fragment of CD28, or (iii) a homolog of (i) or (ii). The crystal of CD28 in a soluble form complexed with the Fab fragment of a mitogenic (superagonistic) antibody has been obtained and used for the determination of the 3D-structure of the receptor. The application also relates to modulators of superagonistic signalling for any receptor of the CD28 family, i.e. to superagonistic antibodies and chimeric proteins thereof, and to the screening of the superagonistic modulators. In the methods of screening, the binding of the candidate modulators to a portion of the receptor proximal to the cell membrane is investigated.

Abstract: The invention relates to a method for identifying T-cell stimulating protein fragments using the following steps: a) detecting the amino acid sequence of an antigen; b) subdividing the found amino acid sequence of the antigen into protein fragments; c) synthesizing at least one protein fragment; d) incubating a suspension containing t-cells with the protein fragments; e) identifying an induced T-cell cytokine or activation marker by flow-through cytometry, and; f) assigning the T-cells, with which T-cell cytokines and/or activation markers were identified, to the protein fragments which were incubated with the T-cells. The corresponding protein fragments/peptides are synthetically produced with the assistance of the detected positive sequence, and said corresponding protein fragments/peptides can be utilized to produce a medicament for immunostimulation.

Abstract: The present invention provides a method of treating BPH using modified pore-forming proteins (MPPs). These MPPs are derived from naturally occurring cytotoxic proteins (nPPs) that kill cells by forming pores or channels in the cell membrane, resulting in cell death. The MPPs are generated by modification of the nPPs such that they are capable of being selectively activated at normal prostate cells. Such modification may include the addition of a prostate-specific protease cleavage site to the activation sequence, and/or the addition of a prostate-specific targeting domain to allow selective targeting of prostate cells. These MPPs are capable of selectively targeting and killing normal prostate cells in vivo. The MPPs may be used either alone or in combination with other therapies for the treatment of BPH.

Abstract: The present invention relates generally to binding agents useful in the selective depletion of T cells in vivo. More specifically, the invention relates to ICOS-binding agents which once bound to ICOS expressed on the surface of cells, in particular ICOS-bearing activated T cells, result in the in vivo depletion of cells to which they are bound. Methods of treating T cell related diseases using said ICOS-binding agents, and pharmaceutical compositions comprising said ICOS-binding agents, a method of identifying an ICOS-binding agent, and monoclonal anti-ICOS antibodies capable of eliminating cells in vivo which express ICOS on their surface are also provided.

Abstract: The present invention relates to a pharmaceutical composition comprising a cyclotide for use in immune suppression as well as to a method for immune suppression comprising the step of administering an effective amount of a pharmaceutical composition comprising such a cyclotide to a subject in need thereof. The present invention also relates to a pharmaceutical composition comprising a cyclotide for use in treating or preventing a disorder selected from the group consisting of (i) an autoimmune disorder; (ii) a hypersensitivity disorder; and (iii) a lymphocyte-mediated inflammation. Likewise, the present invention also relates to a method for treating or preventing a disorder selected from the group consisting of (i) an autoimmune disorder; (ii) a hypersensitivity disorder; and (iii) a lymphocyte-mediated inflammation.

Abstract: A method is provided for preventing rejection by an immune system of a recipient subject of a tissue transplanted from a donor subject into the recipient subject without the need for long-term administration of non-specific immunosuppressive drugs.

Abstract: The present disclosure relates to 2,4-pyrimidinediamines substituted with tricyclic carbamates 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, such as JAK2 or JAK3, is therapeutically useful.

Abstract: The invention provides methods for treating a malignant neoplastic cell proliferative disorder or disease, comprising administering to a subject in need thereof an effective amount of an mTOR inhibitor and an effective amount of a CD4 lymphocyte depleting agent. Such methods find utility in the treatment of certain subsets of malignant neoplastic cell proliferative disorders or diseases, e.g. renal cell carcinoma and melanoma. The invention also provides for pharmaceutical compositions comprising a therapeutically effective amount of an mTOR inhibitor and an effective amount of a CD4 lymphocyte depleting agent in a pharmaceutically acceptable carrier.

Abstract: Described herein are anti-NKG2A antibodies suitable for human therapy, including humanized versions of murine anti-NKG2A antibody Z270, as well as related methods and materials for producing and using such antibodies. Exemplary complementarity-determining regions (CDRs) sequences and sites for optional amino acid back-substitutions in framework region (FR) and/or CDRs of such antibodies are also described.

Abstract: Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.

Abstract: Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single VH or VK domain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen.

Abstract: Improved anti-CD154 antibodies are provided herein which have ablated FcR binding. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.

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: 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 disclosure relates to a protein composed of a first polypeptide or polypeptide domain having a first specific binding activity for Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) expressed on a T-cell cell surface and a second specific binding activity for Glucose Transporter 2 (GLUT2) or an extracellular ectodomain thereof expressed on a pancreatic ?-cell surface, wherein binding of the first polypeptide or polypeptide domain to CTLA-4 induces a CTLA-4 specific agonist response in the T-cell, and binding of the second polypeptide or polypeptide domain to GLUT2 or an ectodomain thereof does not inhibit GLUT2 glucose transporter function, wherein said agonist response in the T-cell induces a response that reduces immunoreactivity against pancreatic ?-cells.

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 present invention relates to antibodies that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Abstract: The invention relates to humanized antibodies directed against the human lymphocyte receptor CD28. When used in a monovalent form these antibodies are antagonists, i.e. capable of blocking of the CD28/B7 interaction, without activating CD28. These antibodies can be used in particular as therapeutic agents for blocking T cell activation through the CD28 receptor.

Abstract: The present invention provides a method for the preparation of a human binding molecule, fragment or derivative thereof which specifically binds to the human CD3 complex. Furthermore, the invention provides a human binding molecules specifically binding to the human CD3 complex and means comprising said human binding molecules.

Abstract: The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.

Abstract: The present invention relates to antagonist antibodies or fragments thereof that bind to human OX40. More specifically, the present invention relates to an antagonist antibody or fragment thereof that binds to human OX40 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6.

Abstract: The present invention comprises a composition with means to inhibit an autoimmune response and methods for using this composition to treat glaucoma and optic neuropathy.

Abstract: Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) and inhibit PD1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD1-mediated functions.