Immuno-adjuvant PDT treatment of metastatic tumors

Abstract

Immuno-adjuvant photodynamic therapy to treat and prevent metastatic cancer is effected using photosensitizers in combination with immuno-adjuvants to destroy metastatic tumor cells.

We claim:  
     
         1 . A method of treating metastatic tumors in a subject, which method comprises: 
 administering to a subject afflicted by metastatic tumors effective amounts of one or more photosensitizer and one or more immuno-adjuvant, and    irradiating said subject with light absorbed by said one or more photosensitizer,    wherein said method is photochemical mediated photodynamic therapy (PDT).    
     
     
         2 . A method of preventing or inhibiting the development of metastatic tumors in a subject, which method comprises: 
 administering to a subject at risk for developing metastatic tumors effective amounts of one or more photosensitizer and one or more immuno-adjuvant, and    irradiating said subject with light absorbed by said one or more photosensitizer.    
     
     
         3 . A method of treating a primary tumor in a subject, which method comprises: 
 administering to a subject clinically diagnosed with a primary tumor effective amounts of one or more photosensitizer and one or more immuno-adjuvant, and    irradiating said subject with light absorbed by said one or more photosensitizer.    
     
     
         4 . The method of  claim 2  wherein said subject has previously undergone cancer or tumor therapy.  
     
     
         5 . The method of  claim 1  wherein said effective amount of one or more photosensitizer is in the range of 0.05 to 10 mg/kg.  
     
     
         6 . The method of  claim 5  wherein said effective amount of one or more photosensitizer is in the range of 0.05 to 1 mg/kg.  
     
     
         7 . The method of  claim 5  wherein said effective amount of one or more photosensitizer is in the range of 1 to 10 mg/kg.  
     
     
         8 . The method of  claim 1  wherein said one or more photosensitizer is administered intravenously and said one or more immuno-adjuvant is administered by injection into tumors after irradiation.  
     
     
         9 . The method of  claim 1  wherein said irradiation is localized to the tumors.  
     
     
         10 . The method of  claim 2  wherein said one or more photosensitizer is administered intravenously or intratumorally.  
     
     
         11 . The method of  claim 1  wherein said one or more photosensitizer is administered, and the subject irradiated, before administration of said one or more immuno-adjuvant.  
     
     
         12 . The method of  claim 1  wherein said one or more immuno-adjuvant is administered systemically.  
     
     
         13 . The method of  claim 1  wherein said one or more photosensitizer is a benzoporphyrin derivative (BPD) or a green porphyrin.  
     
     
         14 . The method of  claim 13  wherein the BPD is BPD-MA, EA6, or B3.  
     
     
         15 . The method of  claim 1  further comprising an additional irradiation, before irradiation with light absorbed by said one or more photosensitizer, with light of a wavelength which improves penetration of the absorbed light.  
     
     
         16 . The method of  claim 1  wherein said one or more immuno-adjuvant comprises mycobacterial cell wall skeleton and/or lipid A from a gram negative bacterium.  
     
     
         17 . The method of  claim 16  wherein said lipid A is de-3-O-acylated lipid A.  
     
     
         18 . The method of  claim 8  further comprising additional systemic administration of immuno-adjuvant to said subject.  
     
     
         19 . The method of  claim 18  wherein said additional systemic administration occurs at least from 1-3 times and occurs at an interval of about two weeks.  
     
     
         20 . The method of  claim 1  further comprising at least 1-3 repeats of the administering and irradiating steps.  
     
     
         21 . The method of  claim 14  wherein said BPD is BPD-MA.  
     
     
         22 . A pharmaceutical composition to treat, prevent, or inhibit the development of, metastatic tumors, said composition comprising: 
 a photosensitizer and an immuno-adjuvant in amounts effective to treat, prevent, or inhibit the development of, metastatic tumors, and    a pharmaceutically acceptable carrier or excipient.    
     
     
         23 . The composition of  claim 22  wherein the photosensitizer is a BPD or a green porphyrin.  
     
     
         24 . The composition of  claim 23  which is a liposomal formulation.  
     
     
         25 . The composition of  claim 23  wherein the BPD is BPD-MA, EA6, or B3.  
     
     
         26 . The composition of  claim 23  wherein said immuno-adjuvant comprises mycobacterial cell wall skeleton and lipid A from a gram negative bacterium.  
     
     
         27 . The composition of  claim 26  wherein said lipid A is de-3-O-acylated lipid A.