Energy-activated targeted cancer therapy

Abstract

The present invention is drawn to methods and systems for administering a therapy to a target tissue or target composition in a mammalian subject, using an ultrasonic energy source that preferably transmits energy to a treatment site transcutaneously. The method provides 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 . A method for transcutaneously administering a therapy to a target tissue in a mammalian subject, comprising the steps of: 
 (a) administering to the subject a therapeutically effective amount of a targeted compound that is activated by ultrasonic energy to render the therapy, where the targeted compound selectively binds to the target tissue, but not to a non-target tissue; and    (b) irradiating at least a portion of the subject with ultrasonic energy at a wavelength that activates the targeted compound, causing the target tissue to be destroyed.    
     
     
         2 . The method of  claim 1 , wherein the step of irradiating is delayed for a period of time sufficient for any of the compound that has not bound to the target tissue to clear from adjacent non-target tissue of the mammalian subject, prior to the step of irradiating.  
     
     
         3 . The method of  claim 1 , wherein the target tissue is selected from the group consisting of a vascular endothelial tissue, an abnormal vascular wall of a tumor, a solid tumor in one of the head, the neck, the gastrointestinal tract, the liver, the breast, the prostate, and the lung, a nonsolid tumor, malignant cells in hematopoietic tissue, malignant cells in lymphoid tissue, lesions in a vascular system, diseased bone marrow, cells afflicted by an autoimmune disease and cells afflicted with an inflammatory disease.  
     
     
         4 . The method of  claim 1 , further comprising the step of providing an ultrasonic emitting source for emitting the ultrasonic energy used for the step of irradiating.  
     
     
         5 . The method  claim 4 , wherein the ultrasonic energy emitting source is disposed external to an intact skin layer.  
     
     
         6 . The method of  claim 1 , wherein said compound includes an energy-activated agent that is conjugated to a ligand.  
     
     
         7 . The method of  claim 6 , wherein the ligand is selected from the group consisting of a target-specific antibody, a target-specific peptide and a target-specific polymer.  
     
     
         8 . The method of  claim 1 , wherein the compound is selected from the group consisting of indocyanine green, methylene blue, toluidine blue, aminolevulinic acid, phthalocyanines, porphyrins, purpurins and texaphyrins.  
     
     
         9 . The method of  claim 1 , wherein the compound is selected from the group consisting of gallium-porphyrin complexes, protoporphyrin, hematoporphyrin, daunorubicin and adriamycin.  
     
     
         10 . The method of  claim 1 , wherein the step of irradiating is carried out for a time interval of from about 30 minutes to about 72 hours.  
     
     
         11 . The method of  claim 1 , wherein the ultrasonic energy used for the step of irradiating is at a frequency between about 5 kHz and more than about 300 MHz.  
     
     
         12 . The method of  claim 1 , wherein the ultrasonic energy used for the step of irradiating is at a frequency between about 20 kHz and more than about 100 MHz.  
     
     
         13 . The method of  claim 1 , wherein the targeted compound activated by ultrasonic energy comprises one of: 
 (a) a targeted compound activated by ultrasonic energy;    (b) a delivery system that delivers the targeted compound activated by ultrasonic energy to bind with the target tissue; or    (c) a prodrug that produces a prodrug product activated by ultrasonic energy, wherein the prodrug product selectively binds to the target tissue.    
     
     
         14 . An ultrasonic energy-activated targeted delivery system that is selectively targeted at a target tissue, comprising: 
 (a) an ultrasonic energy-activated agent that absorbs energy and destroys a target tissue to which it is bound; and    (b) a ligand conjugated to the ultrasonic energy-activated agent, said ligand binding to a receptor on the target tissue with specificity, so that binding of the ligand to a non-target tissue is minimized.    
     
     
         15 . The ultrasonic energy-activated targeted delivery system of  claim 14 , wherein the energy-activated agent comprises a prodrug.  
     
     
         16 . The ultrasonic energy-activated targeted delivery system of  claim 14 , wherein the ligand comprises an antibody that binds to the receptor.  
     
     
         17 . The ultrasonic energy-activated targeted delivery system of  claim 14 , wherein said 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.  
     
     
         18 . The ultrasonic energy-activated targeted delivery system of  claim 14 , wherein the ligand is selected from the group consisting of a target-specific antibody, a target-specific antibody fragment, a target-specific peptide and a target-specific polymer.  
     
     
         19 . The ultrasonic energy-activated targeted delivery system of  claim 14 , 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.  
     
     
         20 . The ultrasonic energy-activated targeted delivery system of  claim 14 , wherein the ligand is a target-specific antibody specific to an antigen selected from the group consisting of tumor surface antigen, tumor endothelial antigen, non-tumor endothelial antigen and tumor vessel wall antigen.