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 cell that has a deficient innate anti-viral response comprising administering to the cell an effective amount of a combination of Myxoma virus and rapamycin. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1  wherein the cell is a human cancer cell. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 4  wherein the Myxoma virus is genetically modified. 
     
     
         7 . The method of  claim 6  wherein the Myxoma virus is genetically modified to express a therapeutic gene. 
     
     
         8 . 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. 
     
     
         9 . The method of  claim 1  wherein the cell is a human cell chronically infected with a virus. 
     
     
         10 . 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 a combination of Myxoma virus and rapamycin. 
     
     
         11 . The method of  claim 10  wherein the disease state is cancer. 
     
     
         12 . The method of  claim 11  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. 
     
     
         13 . The method of  claim 11  wherein the cancer is lung cancer, melanoma, ovarian cancer, prostate cancer, renal cancer, glioma or astrocytoma. 
     
     
         14 . The method of  claim 13  wherein the patient is a human. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 14  wherein the Myxoma virus is genetically modified. 
     
     
         17 . The method of  claim 16  wherein the Myxoma virus is genetically modified to express a therapeutic gene. 
     
     
         18 . The method of  claim 14  wherein the virus and the rapamycin are administered to the site of the cancer by injection. 
     
     
         19 . The method of  claim 14  wherein the virus and the rapamycin are administered systemically. 
     
     
         20 . The method of  claim 10  wherein the disease state is a chronic viral infection. 
     
     
         21 - 40 . (canceled) 
     
     
         41 . A pharmaceutical composition comprising Myxoma virus and rapamycin. 
     
     
         42 - 44 . (canceled) 
     
     
         45 . A method for detecting a cell that has a deficient innate anti-viral response, comprising exposing a population of cells to a combination of 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. 
     
     
         46 . The method of  claim 45  wherein the population of cells is in a patient; said exposing comprises administering to the patient the combination of Myxoma virus and rapamycin, the Myxoma virus being modified to express a detectable marker; and said determining comprises detecting a cell expressing the detectable marker in the patient. 
     
     
         47 . The method of  claim 45  wherein the population of cells is in culture. 
     
     
         48 - 84 . (canceled) 
     
     
         85 . A Myxoma virus that does not express functional M135R. 
     
     
         86 - 95 . (canceled) 
     
     
         96 . The method of  claim 1 , wherein the Myxoma virus does not express functional M135R. 
     
     
         97 . The method of  claim 10 , wherein the Myxoma virus does not express functional M135R. 
     
     
         98 . The pharmaceutical composition of  claim 41 , wherein the Myxoma virus does not express functional M135R. 
     
     
         99 . The method of  claim 45 , wherein the Myxoma virus does not express functional M135R.