Combined cancer treatment methods using therapeutic conjugates that bind to aminophospholipids
AssigneeBoard of Regents, The University of Texas System
InventorsPhilip E. Thorpe, Sophia Ran, Rolf A. Brekken
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Abstract
Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, 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.
Claims54
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;
- and further comprising:
- (a) subjecting said animal to surgery or radiotherapy;
- or
- (b) simultaneously or sequentially administering to said animal a therapeutically effective amount of at least a second anti-cancer agent.
A method for treating cancer, comprising simultaneously or sequentially administering to an animal having a vascularized tumor a therapeutically effective combination of a targeting agent-therapeutic agent construct comprising a therapeutic agent operatively attached to a targeting agent that binds to an aminophospholipid on the luminal surface of blood vessels of the vascularized tumor and at least a second anti-cancer agent.
Dependencies are inferred from the claim text.