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AssigneeThe Corporation of The Trustees of The Sisters of Mercy in Queensland of South Brisbane
InventorsMasato Kato, David Munster, Derek Hart
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The present invention relates generally to a method for modulating the activity of cells of the immune system, including stimulator and responder cells and to agents useful therefor. More particularly, the present invention relates to a method for preventing or down-regulating one or more functional activities of stimulator and responder cells such as, respectively, antigen-presenting cells and lymphocytes inter alia. The present invention further provides antibodies, which interact specifically with epitopes present on the surface of antigen-presenting cells and lymphocytes, resulting in depletion, down-regulation or destruction of targeted antigen-presenting cells and lymphocytes in vivo or in vitro. The instant invention further provides a method for modulating an immune response in a subject and, in particular, for down-regulating the immuno-activity of an allogeneic immuno-competent graft and/or the immune response of a recipient of a solid organ transplant. The ability to modulate stimulator and responder cell immuno-activity may be useful, inter alia, in a range of immuno-therapeutic and immuno-prophylactic treatments that benefit from immune suppression.
A method for modulating immuno-activity of a cell selected from a stimulator myeloid dendritic cell (DC) and a responder CD4+CD8− T cell or CD4−CD8+ T cell said method comprising contacting said cell with an effective amount of an antibody or antigen-binding fragment thereof which couples, binds or otherwise associates with CD83 and in turn prevents, inhibits or otherwise down-regulates one or more functional activities of said cell by inducing cell lysis.
A method for modulating the immuno-activity of a myeloid DC and/or T cell, said method comprising contacting said DC and/or T cell with an effective amount of a monoclonal antibody specific for CD83 for a time and under conditions sufficient to prevent, inhibit or otherwise down-regulate one or more of antigen endocytosis, antigen processing and/or antigen presentation by said DC and activation of macrophages, stimulation of antibody production, and/or killing of target cells by said T cell.
A method for modulating an immune response in a subject, said method comprising administering to said subject an effective amount of an antibody which couples, binds or otherwise associates with a myeloid DC's and/or T cell's surface activation molecule for a time and under conditions sufficient to induce cell lysis of said DC and/or T cell.
A method for down-regulating the immuno-activity of an immuno-competent graft, said method comprising administering to said subject an effective amount of an antibody which couples, binds or otherwise associates with a myeloid DC's and/or a T cell's CD83 molecule, for a time and under conditions sufficient to induce cell lysis of said DC and/or a T cell.
A method for down-regulating the immuno-activity of a bone marrow graft in a subject, said method comprising administering to said subject an effective amount of monoclonal antibody against CD83, for a time and under conditions sufficient to prevent, inhibit or otherwise down-regulate one or more functional activities of a DC and/or T-cell by inducing cell lysis.
A method for the prophylactic and/or therapeutic treatment of a condition characterized by the aberrant, unwanted or otherwise inappropriate immuno-activity of an immuno-competent graft, said method comprising contacting said graft with an effective amount of an antibody or a derivative, homolog, analog, chemical equivalent or mimetic thereof, which couples, binds or otherwise associates with a myeloid DC's and/or a T cell's surface activation CD83 molecule, for a time and under conditions sufficient to prevent, inhibit or otherwise down-regulate the immuno-activity of said DC and/or T cell by inducing cell lysis.
The method of claim 17 wherein the immuno-competent graft comprises allogenic bone marrow cells.
A method for the prophylactic and/or therapeutic treatment of a condition characterized by the aberrant, unwanted or otherwise inappropriate immuno-activity of an immuno-competent graft in a subject, said method comprising contacting said graft with an effective amount of an antibody or a derivative, homolog, analog, chemical equivalent or mimetic thereof, which couples, binds or otherwise associates with a myeloid DC's and/or a T cell's CD83 molecule derived from said graft, for a time and under conditions sufficient to prevent, inhibit or otherwise down-regulate the said inappropriate immuno-activity of said graft by inducing cell lysis.
A method for the prophylactic and/or therapeutic treatment of a condition characterized by an aberrant, unwanted or otherwise inappropriate immune response in a subject, said method comprising administering to said subject an effective amount of an antibody or antigen-binding fragment thereof which couples, binds or otherwise associates with CD83 on the surface of a myeloid DC's and/or a CD4+CD8− T cell or CD4−CD8+ T cell, for a time and under conditions sufficient to prevent, inhibit or otherwise down-regulate the immuno-activity of said DC and/or T cell by inducing cell lysis.
Dependencies are inferred from the claim text.