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.

1 . An energy activatable delivery system that is selectively targeted to a target tissue, comprising:
 an energy activatable agent that destroys a target tissue to which it is bound, the energy activatable agent activatable by absorbing at least one of a sonic, ultrasonic, thermal, or chemical energy; and   a ligand-receptor binding pair comprising:
 a first member conjugated to one of an antibody or an antibody fragment, wherein one of the antibody or the antibody fragment selectively binds to an antigen of the target tissue, and 
 a second member conjugated to the energy activatable agent; 
   wherein the target tissue is selected from among a diseased bone marrow, and malignant cells of one of a hematopoietic tissue and a lymphoid tissue.   
   
   
       2 . The energy activatable targeted delivery system of  claim 1 , wherein the energy activatable agent comprises a prodrug. 
   
   
       3 . The energy activatable targeted delivery system of  claim 1 , wherein the energy activatable agent comprises a sonically or ultrasonically activatable photosensitizing agent. 
   
   
       4 . The energy activatable targeted delivery system of  claim 3  wherein the sonically or ultrasonically activatable photosensitizing agent comprises a chlorin compound. 
   
   
       5 . The energy activatable targeted delivery system of  claim 1 , wherein the target tissue is selected from among malignant cells of one of a hematopoietic tissue and a lymphoid tissue. 
   
   
       6 . The energy activatable targeted delivery system of  claim 1 , wherein the ligand-receptor binding pair comprises an antigen-antibody binding pair. 
   
   
       7 . The energy activatable targeted delivery system of  claim 1 , wherein the energy activatable agent comprises a chlorin compound. 
   
   
       8 . The energy activatable targeted delivery system of  claim 1 , wherein:
 the ligand-receptor binding pair is antigen-antibody; and   the energy activatable agent is a chlorin compound.   
   
   
       9 . The energy activatable targeted delivery system of  claim 1 , wherein:
 the target tissue is a diseased bone marrow; and   the energy activatable agent is a photosensitizer agent activatable by absorbing sonic or ultrasonic energy.   
   
   
       10 . A sonodynamically activatable agent delivery system for treating abnormal, malignant, or diseased target cells, comprising:
 a ligand-receptor binding pair comprising:
 a first member conjugated to one of an antibody or an antibody fragment that selectively binds to an antigen of the target cells; and 
   a second member conjugated to a sonodynamically activatable agent that, when activated, destroys a selectively bound target cell, the sonodynamically activatable agent having a characteristic energy absorption waveband in a sonic or ultrasonic range.   
   
   
       11 . The system of  claim 10 , wherein the ligand-receptor binding pair comprises an antigen-antibody pair. 
   
   
       12 . The system of  claim 10 , wherein the sonodynamically activatable agent comprises a chlorin compound. 
   
   
       13 . A method for treating abnormal, malignant, or diseased target cells in a mammalian subject, comprising:
 administering a therapeutically effective amount of a formulation including a ligand-receptor binding pair comprising
 a first member conjugated to one of an antibody or an antibody fragment, that selectively binds to an antigen of the target tissue, and 
 a second member conjugatable to a sonodynamically activatable agent that, when activated, destroys a target cell, the sonodynamically activatable agent having a characteristic energy absorption waveband in a sonic or ultrasonic range; and 
   activating the sonodynamically activatable agent.   
   
   
       14 . The method of  claim 13  wherein a therapeutically effective amount of a ligand-receptor binding pair comprises an amount sufficient to obtain a blood level of sonodynamically activatable agent of about 0.01 μg/ml to about 100 μg/ml. 
   
   
       15 . The method of  claim 13  wherein a therapeutically effective amount of a ligand-receptor binding pair comprises an amount sufficient to obtain a blood level of sonodynamically activatable agent of about 0.01 μg/ml to about 10 μg/ml. 
   
   
       16 . The method of  claim 13  wherein activating the sonodynamically activatable agent comprises administering ultrasonic energy having an intensity of about 5 mW/cm 2  to about 100 mW/cm 2 .