Energy-activated targeted cancer therapy

Abstract

The present invention is drawn to energy activated targeted delivery systems for administering a therapy to a target tissue or target composition in a mammalian subject, using an energy source that preferably transmits energy to a treatment site transcutaneously. The systems provide for administering to the subject a therapeutically effective amount of a targeted substance, which preferably selectively binds to the target tissue. Energy at a wavelength or waveband corresponding to that which is absorbed by the targeted substance is then administered. The energy intensity is relatively low, but a high total fluence is employed to ensure the activation of the targeted energy-activated agent or targeted prodrug product. The claimed energy-activated targeted therapy is useful in the treatment of specifically selected target tissues, such as vascular endothelial tissue, the abnormal vascular walls of tumors, solid tumors of the head and neck, tumors of the gastrointestinal tract, tumors of the liver, tumors of the breast, tumors of the prostate, tumors of the lung, nonsolid tumors, malignant cells of the hematopoietic and lymphoid tissue and other lesions in the vascular system or bone marrow, and tissue or cells related to autoimmune and inflammatory disease.

What is claimed:  
     
         1 . An energy activated targeted delivery system that is selectively targeted at a target tissue, comprising: 
 (a) an energy activated agent that absorbs energy and destroys a target tissue to which it is bound; and    (b) a ligand conjugated to the energy activated agent, wherein the ligand binds to a receptor on the target tissue with specificity, so that binding of the ligand to a non-target tissue is minimized.    
     
     
         2 . The energy activated targeted delivery system of  claim 1 , wherein the energy activated agent comprises a prodrug.  
     
     
         3 . The energy activated targeted delivery system of  claim 1 , wherein the ligand comprises an antibody fragment that binds to the receptor.  
     
     
         4 . The energy activated targeted delivery system of  claim 1 , wherein the receptor is selected from the group consisting of a vascular endothelium antigen, an antigen that is specific for an abnormal vascular wall of a tumor, and an antigen that is specific for a non-vascular tumor tissue.  
     
     
         5 . The energy activated targeted delivery system of  claim 1 , wherein the ligand comprises an antibody that binds to a receptor.  
     
     
         6 . The energy activated targeted delivery system of  claim 5 , wherein the receptor is selected from the group consisting of a vascular endothelium antigen, an antigen that is specific for an abnormal vascular wall of a tumor, and an antigen that is specific for a non-vascular tumor tissue.  
     
     
         7 . The energy activated targeted delivery system of  claim 5 , wherein the ligand and the receptor comprise a binding pair selected from the group consisting of: a biotin-streptavidin, a chemokine-chemokine receptor, a growth factor-growth factor receptor, and an antigen-antibody.  
     
     
         8 . The energy activated targeted delivery system of  claim 1 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         9 . The energy activated targeted delivery system of  claim 2 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         10 . The energy activated targeted delivery system of  claim 3 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         11 . The energy activated targeted delivery system of  claim 4 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         12 . The energy activated targeted delivery system of  claim 5 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         13 . The energy activated targeted delivery system of  claim 6 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         14 . The energy activated targeted delivery system of  claim 7 , wherein the energy activated agent is a photosensitizing agent.  
     
     
         15 . The energy activated targeted delivery system of  claim 8 , wherein the photosensitizing agent is selected from the group consisting of indocyanine green, methylene blue, toluidine blue; aminolevulinic acid, chlorin compounds, phthalocyanines, porphyrins, purpurins, and texaphyrins.  
     
     
         16 . The energy activated targeted delivery system of  claim 1 , wherein the energy activated agent is activated by irradiating with ultrasonic energy.  
     
     
         17 . The energy activated targeted delivery system of  claim 1 , wherein the ligand comprises a peptide specific in binding with the target tissue.  
     
     
         18 . An energy-activated targeted delivery system that is selectively targeted at a target tissue, comprising: 
 (a) an energy-activated agent that absorbs energy and destroys a target tissue to which it is bound;    (b) a first member of a ligand-receptor binding pair conjugated to one of an antibody and an antibody fragment, wherein one of the antibody and the antibody fragment selectively binds to an antigen of the target tissue; and    (c) a second member of the ligand-receptor binding pair, conjugated to the energy-activated agent.