Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
AssigneeThe UAB Research Foundation
InventorsTong Zhou, Kimihisa Ichikawa, Robert P Kimberly, William J Koopman
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Abstract
An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.
Claims126
A purified antibody which binds a TRAIL receptor DR5, wherein said antibody, in its soluble form at low concentrations, has in vivo and in vitro cell death-inducing activity in target cells expressing DR5.
A monoclonal antibody having the same epitope specificity as mouse-mouse hybridoma TRA-8 having ATCC Accession Number PTA-1428.
A monoclonal antibody produced by mouse-mouse hybridoma TRA-8 having ATCC Accession Number PTA-1428.
A method of selectively inducing cell death in target cells comprising the steps of:
- (a) transfecting the target cells with a vector comprising an expressible TRAIL receptor nucleic acid sequence;
- (b) expressing on said cells a TRAIL receptor encoded by said TRAIL receptor nucleic acid sequence;
- and
- (c) contacting said cells with a cell death-inducing antibody selective for binding said TRAIL receptor.
An isolated nucleic acid, comprising a nucleotide sequence that encodes a heavy chain immunoglobulin of an antibody capable of binding TRAIL receptor DR5 and capable of inducing cell death of a cell with DR5 receptors.
A purified polypeptide comprising an amino acid sequence of a heavy chain immunoglobulin of an antibody capable of binding TRAIL receptor DR5 and capable of inducing cell death of a cell with DR5 receptors.
An isolated nucleic acid, comprising a nucleotide sequence that encodes a light chain immunoglobulin of an antibody capable of binding TRAIL receptor DR5 and capable of inducing cell death of a cell with DR5 receptors.
A purified polypeptide comprising an amino acid sequence of a light chain immunoglobulin of an antibody capable of binding TRAIL receptor DR5 and capable of inducing cell death of a cell with DR5 receptors.
Dependencies are inferred from the claim text.