Combinations of Antibodies Selective for a Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor and Other Therapeutic Agents
AssigneeThe UAB Research Foundation
InventorsRobert P. Kimberly, William J. Koopman, Albert F. LoBuglio, Tong Zhou, Donald J. Buchsbaum, Kimihisa Ichikawa, Jun Oshumi
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Abstract
An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.
Claims74
A method of selectively inducing apoptosis in target cells expressing DR5, comprising the steps of (a) contacting the target cells with a soluble antibody that specifically binds TRAIL receptor DR5 and (b) contacting the target cells with a therapeutic quantity of one or more therapeutic agents, wherein the antibody is present in amounts sufficient to kill target cells expressing DR5, wherein the antibody induces cell death of target cells expressing DR5 in vitro in the absence of crosslinking by a secondary antibody and at concentrations less than 1 μg/ml, wherein the antibody induces cell death of target cells expressing DR5 in vivo and wherein the antibody does not bind TRAIL receptor DR4, DcR1 or DcR2.
A method of inhibiting proliferation of target cells expressing DR5, comprising the steps of (a) contacting the target cells with a soluble antibody that specifically binds TRAIL receptor DR5 and (b) contacting the target cells with a therapeutic quantity of one or more therapeutic agents, wherein the antibody is present in amounts sufficient to kill target cells expressing DR5, wherein the antibody induces cell death of target cells expressing DR5 in vitro in the absence of crosslinking by a secondary antibody and at concentrations less than 1 μg/ml, wherein the antibody induces cell death of target cells in vivo, and wherein the antibody does not bind TRAIL receptor DR4, DcR1 or DcR2.
A method of treating an inflammatory or autoimmune disease in a subject, comprising (a) administering to the subject a soluble antibody that specifically binds TRAIL receptor DR5 and (b) administering to the subject a therapeutic quantity of a therapeutic agent, wherein the antibody is present in amounts sufficient to kill target cells expressing DR5, wherein the antibody induces cell death of target cells expressing DR5 in vitro in the absence of crosslinking by a secondary antibody and at concentrations less than 1 μg/ml, wherein the antibody induces cell death of target cells expressing DR5 in vivo, and wherein the antibody does not bind TRAIL receptor DR4, DcR1 or DcR2.
A composition comprising (a) a soluble antibody that specifically binds TRAIL receptor DR5 and (b) one or more therapeutic agents, wherein the antibody is present in amounts sufficient to kill target cells expressing DR5, wherein the antibody induces cell death of target cells expressing DR5 in vitro in the absence of crosslinking by a secondary antibody and at concentrations less than 1 μg/ml, wherein the antibody induces cell death of target cells in vivo and wherein the antibody does not bind TRAIL receptor DR4, DcR1 or DcR2.
Dependencies are inferred from the claim text.