Cancer treatment methods using therapeutic conjugates that bind to aminophospholipids
AssigneeBoard of Regents, The University of Texas System
InventorsPhilip E. Thorpe, Sophia Ran
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Abstract
Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolaminie, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.
Claims50
A method for killing tumor vascular endothelial cells, comprising administering to an animal having a vascularized tumor a biologically effective amount of at least a first binding ligand;
- wherein said binding ligand comprises a selected cytotoxic agent operatively attached to a targeting agent and wherein said targeting agent binds to an aminophospholipid on the luminal surface of tumor vascular endothelial cells.
A method for inducing tumor vasculature coagulation, comprising administering to an animal having a vascularized tumor a vessel-occluding amount of at least a first binding ligand;
- wherein said binding ligand comprises a selected occluding agent operatively attached to a targeting agent and wherein said targeting agent binds to an aminophospholipid on the luminal surface of tumor vasculature.
A method for destroying tumor vasculature, comprising administering to an animal having a vascularized tumor a tumor-destructive amount of at least a first binding ligand;
- wherein said binding ligand comprises a selected destructive agent operatively attached to a targeting agent and wherein said targeting agent binds to an aminophospholipid on the luminal surface of blood vessels of the vascularized tumor.
A method for treating an animal having a vascularized tumor, comprising administering to said animal a therapeutically effective amount of at least a first binding ligand;
- wherein said binding ligand comprises at least a first therapeutic agent operatively attached to a targeting agent and wherein said targeting agent binds to an aminophospholipid on the luminal surface of blood vessels of a vascularized tumor.
A method for treating cancer, comprising administering to an animal having a vascularized tumor at least a first pharmaceutical composition comprising an amount of at least a first binding ligand effective to kill at least a portion of the intratumoral vascular endothelial cells;
- wherein said binding ligand comprises at least a first cytotoxic agent operatively attached to a targeting agent and wherein said targeting agent binds to an aminophospholipid expressed on the luminal surface of intratumoral blood vessels of the vascularized tumor.
A method for treating cancer, comprising administering to an animal having a vascularized tumor at least a first pharmaceutical composition comprising an amount of at least a first binding ligand effective to occlude or destroy intratumoral vasculature, the binding ligand comprising at least a first coagulative or destructive agent operatively attached to a targeting agent that binds to an aminoplhospholipid expressed on the luminal surface of intratumoral blood vessels of the vascularized tumor.
A method for treating cancer, comprising administering to an animal with a vascularized tumor at least a first pharmaceutical composition comprising an amount of at least a first binding ligand effective to induce tumor necrosis, the binding ligand comprising at least a first therapeutic agent operatively attached to a targeting agent that binds to an aminophospholipid expressed on the luminal surface of intratumoral blood vessels of the vascularized tumor.
A method for treating an animal having a vascularized tumor, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising at least a first construct comprising an anti-aminophospholipid antibody, or antigen binding fragment thereof, directly or indirectly linked to at least a first therapeutic agent.
A method for delivering a selected therapeutic agent to tumor vasculature, comprising administering to an animal having a vascularized tumor a biologically effective amount of at least a first binding ligand;
- wherein said binding ligand comprises said selected therapeutic agent operatively attached to a targeting agent and wherein said targeting agent binds to an aminophospholipid on the luminal surface of blood vessels of the vascularized tumor.
Dependencies are inferred from the claim text.