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.

1 . A method for inhibiting a cancer cell that has a deficient innate anti-viral response comprising administering to the cell an effective amount of a combination of a replication-competent Myxoma virus and rapamycin. 
     
     
         2 . The method of  claim 1 , wherein the cell is a human cancer cell. 
     
     
         3 . The method of  claim 2 , wherein the Myxoma virus is genetically modified. 
     
     
         4 . The method of  claim 3 , wherein the Myxoma virus is genetically modified to express a therapeutic gene. 
     
     
         5 . The method of  claim 2 , wherein the cell is a lung cancer cell, a melanoma cell, an ovarian cancer cell, a prostate cancer cell, a renal cancer cell, a glioma cell or an astrocytoma cell. 
     
     
         6 . The method of  claim 2 , wherein the cancer is a solid tumour, hematopoietic cell cancer, colon cancer, pancreas cancer, endometrial cancer, thyroid cancer, oral cancer, laryngeal cancer, hepatocellular cancer, bile duct cancer, squamous cell carcinoma, breast cancer, cervical cancer, or colorectal cancer. 
     
     
         7 . The method of  claim 1 , wherein the cell is in culture. 
     
     
         8 . The method of  claim 1 , wherein the Myxoma virus does not express functional M135R. 
     
     
         9 . (canceled) 
     
     
         10 . A method for treating a disease state characterized by the presence of cancer cells, comprising administering to a patient in need thereof an effective amount of a combination of a replication-competent Myxoma virus and rapamycin. 
     
     
         11 . The method of  claim 10 , wherein the Myxoma virus does not express functional M135R. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 10 , wherein the cancer cell is a lung cancer cell, a melanoma cell, an ovarian cancer cell, a prostate cancer cell, or a renal cancer cell. 
     
     
         14 . The method of  claim 13 , wherein the patient is a human. 
     
     
         15 . The method of  claim 14 , wherein the Myxoma virus is genetically modified. 
     
     
         16 . The method of  claim 15 , wherein the Myxoma virus is genetically modified to express a therapeutic gene. 
     
     
         17 . The method of  claim 14 , wherein the virus and the rapamycin are administered to the site of the cancer by injection. 
     
     
         18 . The method of  claim 14 , wherein the virus and the rapamycin are administered systemically. 
     
     
         19 . (canceled) 
     
     
         20 . A pharmaceutical composition comprising Myxoma virus and rapamycin. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the Myxoma virus does not express functional M135R. 
     
     
         22 . A method for detecting a cancer cell, comprising exposing a population of cells to a combination of a replication-competent Myxoma virus and rapamycin; allowing the virus to infect a cell that has a deficient innate anti-viral response; and determining the infection of any cells of the population of cells by the Myxoma virus. 
     
     
         23 . The method of  claim 22 , wherein the Myxoma virus does not express functional M135R. 
     
     
         24 . The method of  claim 10 , wherein the Myxoma virus is administered to the site of the cancer by injection and the cancer cells are glioma cells or astrocytoma cells. 
     
     
         25 . The method of  claim 14 , wherein the Myxoma virus is administered to the site of the cancer by injection.