Use of a combination of myxoma virus and rapamycin for therapeutic treatment

Abstract

The present invention relates to therapeutic use of a combination of Myxoma virus, including in combination with rapamycin. Treatment with rapamycin enhances the ability of Myxoma virus to selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon. The combination of rapamycin and Myxoma virus can be used to treat diseases characterized by the presence of such cells, including cancer. The invention also relates to therapeutic use of Myxoma virus that does not express functional M135R.

What is claimed is: 
     
         1 . A method for inhibiting a cell that has a deficient innate anti-viral response comprising administering to the cell an effective amount of Myxoma virus that does not express functional M135R. 
     
     
         2 . The method of  claim 1  wherein the cell is non-responsive to interferon. 
     
     
         3 . The method of  claim 2  wherein the cell exhibits abnormal interferon signalling. 
     
     
         4 . The method of  claim 3  wherein the cell is a human cancer cell. 
     
     
         5 . The method of  claim 4  wherein the Myxoma virus is genetically modified to express a therapeutic gene. 
     
     
         6 . The method of  claim 4  wherein the cell is lung cancer cell, melanoma cell, ovarian cancer cell, prostate cancer cell, renal cancer cell, glioma cell or astrocytoma cell. 
     
     
         7 . The method of  claim 1  wherein the cell is a human cell chronically infected with a virus. 
     
     
         8 . A method for treating a disease state characterized by the presence of cells that have a deficient innate anti-viral response, comprising administering to a patient in need thereof an effective amount of Myxoma virus that does not express functional M135R. 
     
     
         9 . The method of  claim 8  wherein the disease state is cancer. 
     
     
         10 . The method of  claim 9  wherein the cancer is a solid tumour, hematopoietic cell cancer, colon cancer, lung cancer, kidney cancer, pancreas cancer, endometrial cancer, thyroid cancer, oral cancer, ovarian cancer, laryngeal cancer, hepatocellular cancer, bile duct cancer, squamous cell carcinoma, prostate cancer, breast cancer, cervical cancer, colorectal cancer or melanoma. 
     
     
         11 . The method of  claim 9  wherein the cancer is lung cancer, melanoma, ovarian cancer, prostate cancer, renal cancer, glioma or astrocytoma. 
     
     
         12 . The method of  claim 11  wherein the patient is a human. 
     
     
         13 . The method of  claim 12  wherein the Myxoma virus is genetically modified to express a therapeutic gene. 
     
     
         14 . The method of  claim 9  wherein the virus is administered to the site of the cancer by injection. 
     
     
         15 . The method of  claim 9  wherein the virus is administered systemically. 
     
     
         16 . The method of  claim 8  wherein the disease state is a chronic viral infection. 
     
     
         17 . A Myxoma virus that does not express functional M135R. 
     
     
         18 . A pharmaceutical composition comprising Myxoma virus that does not express functional M135R. 
     
     
         19 . The pharmaceutical composition of  claim 18  further comprising an additional therapeutic agent. 
     
     
         20 . The pharmaceutical composition of  claim 19  wherein the additional therapeutic agent is a chemotherapeutic agent. 
     
     
         21 . A kit comprising Myxoma virus that does not express functional M135R and instructions for inhibiting a cell that has a deficient innate anti-viral response or for treating a disease state characterized by the presence of cells that have a deficient innate anti-viral response.