477 results about "Effector cell" patented technology

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 FcgammaRIIA and / or FcgammaRIIA 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 FcgammaR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention relates to methods and compositions for the treatment of Hodgkin's Disease, comprising administering proteins characterized by their ability to bind to CD30, or compete with monoclonal antibodies AC10 or HeFi-1 for binding to CD30, and exert a cytostatic or cytotoxic effect on Hodgkin's disease cells in the absence of effector cells or complement. Such proteins include derivatives of monoclonal antibodies AC10 and HeFi-1. The proteins of the invention can be human, humanized, or chimeric antibodies; further, they can be conjugated to cytotoxic agents such as chemotherapeutic drugs. The invention further relates to nucleic acids encoding the proteins of the invention. The invention yet further relates to a method for identifying an anti-CD30 antibody useful for the treatment or prevention of Hodgkin's Disease.

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 FcgammaRIIIA and / or FcgammaRIIA 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 FcgammaR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

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 FcγRIIIA and / or FcγRIIA 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 FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention relates to methods and compositions for the treatment of Hodgkin's Disease, comprising administering proteins characterized by their ability to bind to CD30, or compete with monoclonal antibodies AC10 or HeFi-1 for binding to CD30, and exert a cytostatic or cytotoxic effect on Hodgkin's disease cells in the absence of effector cells or complement. Such proteins include derivatives of monoclonal antibodies AC10 and HeFi-1. The proteins of the invention can be human, humanized, or chimeric antibodies; further, they can be conjugated to cytotoxic agents such as chemotherapeutic drugs. The invention further relates to nucleic acids encoding the proteins of the invention. The invention yet further relates to a method for identifying an anti-CD30 antibody useful for the treatment or prevention of Hodgkin's Disease.

The present invention relates to methods of treating or preventing cancer and other diseases using 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 FcγRIIIA and / or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease. The methods of the invention are also of use in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention relates to methods and compositions for the treatment of Hodgkin's Disease, comprising administering proteins characterized by their ability to bind to CD30, or compete with monoclonal antibodies AC10 or HeFi-1 for binding to CD30, and exert a cytostatic or cytotoxic effect on Hodgkin's disease cells in the absence of effector cells or complement. Such proteins include derivatives of monoclonal antibodies AC10 and HeFi-1. The proteins of the invention can be human, humanized, or chimeric antibodies; further, they can be conjugated to cytotoxic agents such as chemotherapeutic drugs. The invention further relates to nucleic acids encoding the proteins of the invention. The invention yet further relates to a method for identifying an anti-CD30 antibody useful for the treatment or prevention of Hodgkin's Disease.

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 FcγRIIIA and / or FcγRIIA 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 FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention is directed to mammalian bi-specific T cells and methods for using these bi-specific T cells. More specifically, the invention relates to viral specific T cells that express chimeric anti-tumor receptors. These bi-specific T cell clones are a source of effector cells that persist in vivo in response to stimulation with viral antigen, leading to long-term function after their transfer to patients with cancer and autoimmune diseases.

The invention discloses a full-humanized anti-PD-1 monoclonal antibody having a heavy-chain amino acid sequence shown in a sequence 7 in a sequence table and a light-chain amino acid sequence shown in a sequence 8 in the sequence table. The full-humanized anti-PD-1 monoclonal antibody has the advantages that the antibody has high appetency and low immunogenicity on PD-1, is efficiently expressed in animal cells, and can be used for industrial production. An experiment proves that the full-humanized anti-PD-1 monoclonal antibody specifically blocks a PD-1 / PD-L inhibiting signal, so that a disabled effector cell in an organism restores a biological function; activation proliferation of a tumor and a virus specificity CD8+T cell and secretion of a cell factor are facilitated; the killability of lymphocyte on tumor antigen, an exotic invasive virus and the like is enhanced; the immunity of the organism is improved; and the tumor cell and the virus are timely cleared. Therefore, the antibody disclosed by the invention has a wide application prospect on treatment of tumors, infectious diseases and autoimmune diseases.

Disclosed are synthetic nanocarrier methods, and related compositions, comprising administering immunosuppressants and MHC Class I-restricted and / or MHC Class II-restricted epitopes that can generate tolerogenic immune responses (e.g., antigen-specific T effector cell deletion).

The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant heavy chain, which variant heavy chain comprises constant domains from more than one IgG isotype. The variant heavy chain of the invention may further comprise at least one amino acid modification relative to the parental heavy chain, such that the Fc region of said variant heavy chain binds an FcγR with an altered affinity relative to a comparable molecule comprising the wild-type heavy cahin. 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 FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention relates to Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and to methods of using such polypeptides for treating or preventing cancer and other diseases. The Fc region-containing polypeptides of the present invention are preferably immunoglobulins (e.g., antibodies), in which the Fc region comprises at least one amino acid substitution relative to the corresponding amino acid sequence of a wild type Fc region, and which is sufficient to attenuate post-translational fucosylation and mediate improved binding to an activating Fc receptor and reduced binding to an inhibitory Fc receptor. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).

The present invention relates to methods of treating or preventing cancer and other diseases using 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 an FcγR that activates a cellular effector (“FcγRActivating,” such as FcγRIIA or FcγRIIIA) and an FcγR that inhibits a cellular effector (“FcγRInhibiting,” such as FcγRIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such FcγR for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).

Methods and devices are provided herein for identifying a cell population comprising an effector cell that exerts an extracellular effect. In one embodiment the method comprises retaining in a microreactor a cell population comprising one or more effector cells, wherein the contents of the microreactor further comprise a readout particle population comprising one or more readout particles, incubating the cell population and the readout particle population within the microreactor, assaying the cell population for the presence of the extracellular effect, wherein the readout particle population or subpopulation thereof provides a direct or indirect readout of the extracellular effect, and determining, based on the results of the assaying step, whether one or more effector cells within the cell population exerts the extracellular effect on the readout particle. If an extracellular effect is measured, the cell population is recovered for further analysis to determine the cell or cells responsible for the effect.

A murine anti-CD20 monoclonal antibody having cell growth inhibitory activities is disclosed. Cell growth inhibitory activities include apoptosis against human CD20 antigen expressing cells in culture of the CD20 antigen expressing cells without effector cells. The anti-CD20 monoclonal antibody is incorporated into chimeric anti-CD20 monoclonal antibodies in which the amino acid sequences of the variable regions of the anti-CD20 monoclonal antibody and the amino acid sequences of the constant regions of human immunoglobulin are fused. Also a humanized anti-CD20 monoclonal antibody is described which includes all of the variable region CDRs of the H chain of the anti-CD20 monoclonal antibody and all of the variable region CDRs of the L chain of the anti-CD20 monoclonal antibody and an amino acid sequence of human immunoglobulin. A nucleotide sequence encoding the amino acid sequence of the chimeric or humanized anti-CD20 monoclonal antibody can be expressed in mammalian cells.

A redirected Treg cell is endowed with specificity toward a selected target antigen or ligand. The cell contains a chimeric receptor polypeptide that is expressed in a single, continuous chain, with an extracellular recognition region displayed on the surface of the cell, a transmembrane region and an intracellular signaling region. The extracellular recognition region is specific for the selected target antigen or ligand. The intracellular signaling region includes a combination of T-cell signaling polypeptide moieties, which combination, upon binding of the extracellular recognition region to the selected target antigen or ligand, triggers activation of the redirected Treg cells to cause suppression of T-cell mediated immunity. Such redirected Treg cells may be used to suppress undesired activity of T effector cells thereby mediating an immune or inflammatory response. They are particularly useful in treating T effector cell-mediated diseases, such as inflammatory bowel disease, transplant rejection and GVH disease.

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 FcγRIIIA and / or FcγRIIA 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 FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

This invention relates to specific antibodies against ganglioside GD3 called MB3.6 and against protein prostate specific membrane antigen (PSMA) called 3D8, 4D4 and 3E11 when prepared as chimeric molecules with signaling molecules of T cells and other effector cells, and the use thereof in the treatment of cancers expressing these antigens.

The present invention is based, at least in part, on the finding that certain molecules are preferentially associated with effector T cells or regulatory T cells. Accordingly, immune responses by one or the other subset of cells can be preferentially modulated. The invention pertains, e.g., to methods of modulating (e.g., up- or down-modulating), the balance between the activation of regulatory T cells and effector T cells leading to modulation of immune responses and to compositions useful in modulating those responses. The invention also pertains to methods useful in diagnosing, treating, or preventing conditions that would benefit from modulating effector T cell function relative to regulatory T cell function or from modulating regulatory T cell function relative to effector T cell function in a subject. The subject methods and compositions are especially useful in the diagnosis, treatment or prevention of conditions characterized by a too-vigorous effector T cell response to antigens associated with the condition, in the diagnosis, treatment or prevention of conditions characterized by a weak effector T cell response, in the diagnosis, treatment or prevention of conditions characterized by a too-vigorous regulatory T cell response, or in the diagnosis, treatment, or prevention of conditions characterized by a weak regulatory T cell response.

The present invention relates to methods and pharmaceutical compositions useful for the prevention and treatment of any disease wherein the treatment of such disease would be improved by an enhanced immune response, such as infectious diseases, primary and metastatic neoplastic diseases (i.e., cancer), or neurodegenerative or amyloid diseases. In particular, the contemplated invention is directed to method comprising the administration of heat shock / stress proteins (HSPs) or HSP complexes alone or in combination with each other, in combination with the administration of an immunoreactive reagent. The invention also provides pharmaceutical compositions comprising one or more HSPs or HSP complexes in combination with an immunoreactive reagent. Additionally, the invention contemplates the use of the methods and compositions of the invention to enhance or improve passive immunotherapy and effector cell function.

Compositions containing clinically relevant numbers of immune cells that have been isolated from a patient differentiated and / or expanded ex vivo. Methods for treating or preventing disease or otherwise altering the immune status of the patient by reinfusing such cells into the donor are also provided. Methods for expanding and / or immune cells, including effector cells, in the absence of exogenous IL-2, and for administering the cells in the absence of co-infused IL-2 are also provided.

Compositions containing clinically relevant numbers of immune cells that have been isolated from a patient differentiated and / or expanded ex vivo. Methods for treating or preventing disease or otherwise altering the immune status of the patient by reinfusing such cells into the donor are also provided. Methods for expanding and / or immune cells, including effector cells, in the absence of exogenous IL-2, and for administering the cells in the absence of co-infused IL-2 are also provided.

The present invention relates to methods of treating or preventing cancer and other diseases using 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 an FcγR that activates a cellular effector (“FcγRActivating,” such as FcγRIIA or FcγRIIIA) and an FcγR that inhibits a cellular effector (“FcγRInhibiting,” such as FcγRIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such FcγR for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmunde disease).

Hematopoeitic stem / progenitor cells (HSPC) and / or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.