Therapeutic regimen for treating cancer

Abstract

The invention provides a method for treating cancer in a human comprising administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding TNF-α operably linked to a promoter, wherein the dose comprises about 1×10 7 to about 4×10 12 particle units (pu) of replication-deficient adenoviral vector, at least once in a therapeutic period comprising up to 10 weeks, whereby the cancer in human is treated. The invention further provides a method of treating a human for multiple tumors, wherein the method comprises contacting a first tumor with a dose of the pharmaceutical composition at least once in a therapeutic period comprising up to about 10 weeks, whereby the human is treated for the first tumor and one or more additional tumors.

1 . A method of treating a human for multiple tumors, wherein the method comprises directly administering to a first tumor a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding TNF-α and operably linked to a promoter, wherein the dose comprises about 1×10 7  to about 4×10 12  particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, whereby the human is treated for the first tumor and one or more additional tumors.  
   
   
       2 . The method of  claim 1 , wherein tumor cells within the first tumor and one or more additional tumors are destroyed.  
   
   
       3 . The method of  claim 2 , wherein the size of the first tumor and one or more additional tumors is reduced.  
   
   
       4 . The method of  claim 3 , wherein the adenoviral vector is replication-deficient.  
   
   
       5 . The method of  claim 4 , wherein the method further comprises administering a dose of ionizing radiation to the tumor over the duration of the therapeutic period.  
   
   
       6 . The method of  claim 4 , wherein the promoter is EGR-1.  
   
   
       7 . The method of  claim 1 , wherein the dose of ionizing radiation comprises about 20 Grays (Gy) to about 70 Gy administered over the duration of the therapeutic period.  
   
   
       8 . The method of  claim 1 , wherein the first tumor is a solid tumor.  
   
   
       9 . The method of  claim 8 , wherein the first tumor is located in the breast, pancreas, colon, rectum, head, neck, brain, esophagus, or lung.  
   
   
       10 . The method of  claim 8 , wherein the first tumor is located in the bladder, thyroid, mandible, skin, or kidney.  
   
   
       11 . The method of  claim 8 , wherein the therapeutic period comprises up to six weeks, and the method comprises administering two doses of pharmaceutical composition in weeks 1-2 and one dose of pharmaceutical composition in each subsequent week of the therapeutic period.  
   
   
       12 . The method of  claim 8 , wherein the pharmaceutical composition is administered to the first tumor via 2-5 injections.  
   
   
       13 . The method of  claim 1 , wherein the first tumor is soft tissue sarcoma.  
   
   
       14 . The method of  claim 13 , wherein the therapeutic period comprises about five weeks, and the method comprises administering two doses of pharmaceutical composition in week 1 and one dose of pharmaceutical composition in each subsequent week of the therapeutic period.  
   
   
       15 . The method of  claim 13 , wherein the pharmaceutical composition is administered to the first tumor via 3-8 injections.  
   
   
       16 . The method of  claim 1 , wherein the first tumor and the one or more additional tumors are located in different regions of the body of the human.