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AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsNeelima Bhat, Marcia Bieber, Nelson Teng, Martin Sanders
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Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.
A composition for inducing cell membrane wounding, comprising a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell, wherein said cell surface antigen is associated with the cytoskeleton of the cell.
A composition for augmenting cell membrane wounding in a lymphoid cell, comprising a polyvalent agent that binds to a highly expressed cell surface antigen on a lymphoid cell, and further comprising a crosslinking agent that augments the cell membrane wounding of the polyvalent agent relative to the cell membrane wounding of the polyvalent agent in the absence of the crosslinking agent.
A composition for killing a cell, comprising a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell, and further comprising a crosslinking agent providing crosslinking of the polyvalent agent.
A composition for permeabilizing a cell, comprising a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell.
A composition for inducing cell membrane wounding in B cells, comprising a polyvalent VH4-34 antibody that binds to a cell surface antigen on the surface of the B cell.
A pharmaceutical composition for treating a mammal suffering from a condition characterized by hyperproliferation of cells, said pharmaceutical composition comprising a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell, wherein said polyvalent agent induces cell membrane wounding.
A composition for augmenting cell membrane wounding induced by a cell membrane wounding antibody, comprising a polyvalent antibody that binds to a highly expressed cell surface antigen, and crosslinking means that augments the cytotoxicity of the polyvalent antibody, wherein the crosslinking means augments the cytotoxicity of the polyvalent antibody relative to the cytotoxicity of the polyvalent antibody in the absence of the crosslinking means.
A pharmaceutical composition for treating a mammal suffering from a condition characterized by hyperproliferation of cells, comprising a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell, wherein said polyvalent agent comprises a plurality of binding sites for the cell surface antigen on the surface of the cell.
A method of treating a mammal suffering from a condition characterized by a hyperproliferation of cells, comprising administering a polyvalent agent that binds a highly expressed cell surface receptor on the surface of the hyperproliferating cells, wherein said polyvalent agent is administered in an amount effective to preferentially kill the hyperproliferating cells relative to normal cells.
A method of killing a cancer cell, comprising contacting a cancer cell with a cytotoxic amount of a cell membrane wounding antibody that binds to a highly-expressed cell surface antigen on the surface of the cancer cell and induces cell membrane wounding in the cancer cell.
A method for inducing cell membrane wounding in a lymphoid cell in a human patient, comprising contacting a cell with a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of the lymphoid cell.
A method for inducing cell membrane wounding, comprising contacting a cell with a polyvalent agent that binds to a highly expressed cell surface antigen on the surface of the cell.
A method for permeabilizing a cell, comprising contacting a cell with a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of the cell.
A method of treating a human patient suffering from a condition characterized by a hyperproliferation of B cells, comprising contacting said B cells with (1) a cytotoxic amount of an antibody having specific binding for CDIM epitopes on a B cell, and (2) a crosslinking agent that crosslinks the antibody having specific binding for CDIM epitopes on a B cell.
A method of purging the bone marrow of malignant B cells from a patient in need thereof is provided, comprising contacting the bone marrow cells with an antibody having specific binding for a CDIM epitope on the surface of the B cells, and further comprising contacting the B cells with a crosslinking agent that crosslinks the antibody bound to the CDIM epitope on the surface of the B cells, thereby providing an enhanced cytotoxicity for the anti-CDIM antibody toward the malignant B cells.
A kit for determining the dose threshold to a polyvalent agent that induces cell membrane wounding in a mammal, comprising a sufficient amount of a polyvalent agent that binds to a highly expressed cell surface antigen to perform binding assays.
A kit for determining the dose threshold to a cell membrane wounding antibody in a mammal, comprising a sufficient amount of a cell wounding antibody that binds to a highly expressed cell surface antigen to perform binding assays, a crosslinking agent, or a cytotoxic agent, or combinations thereof.
Dependencies are inferred from the claim text.