Cancer treatment kits comprising 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.
Claims35
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anticancer agent, wherein said at least a first anti-cancer agent is at least a first targeting agent-therapeutic agent construct that comprises at least a first targeting agent operatively attached to at least a first therapeutic agent, wherein said at least a first targeting agent binds to phosphatidylethanolamine expressed on the luminal surface of blood vessels of a vascularized tumor, and
- (b) at least a second anti cancer agent other than said at least a first targeting agent-therapeutic agent construct.
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anti-cancer agent, wherein said at least a first anticancer agent is at least a first targeting agent-therapeutic agent construct that comprises at least a first targeting agent operatively attached to at least a first therapeutic agent, wherein said at least a first targeting agent binds to phosphatidylethanolamine on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first targeting agent-therapeutic agent construct;
- wherein said at least a second anti-cancer agent:
- (i) increases phosphatidylethanolamine expression in the endothelium of said blood vessels of said vascularized tumor or injures or induces apoptosis in the endothelium of said blood vessels of said vascularized tumor, or
- (ii) kills tumor cells of said tumor or is an anti-angiogenic agent that inhibits metastasis of tumor cells.
In combination, biologically effective amounts of:
- (a) a first composition comprising at least a first anti cancer agent, wherein said at least a first anti-cancer agent is at least a first targeting agent-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first targeting agent that binds to phosphatidylethanolamine;
- (b) a second composition comprising a targeting agent-detectable agent construct that comprises a detectable agent operatively attached to a second targeting agent that binds to phosphatidylethanolamine;
- and
- (c) at least a second anti-cancer agent other than said at least a first targeting agent-therapeutic agent construct.
Dependencies are inferred from the claim text.