Reovirus for the treatment of neoplasia

Abstract

Methods for treating neoplasia, by administering reovirus to a Ras-mediated neoplasm, are disclosed. The reovirus is administered so that it ultimately directly contacts cells of the neoplasm. Human reovirus, non-human mammalian reovirus, and/or avian reovirus can be used. If the reovirus is human reovirus, type 1 (e.g., strain Lang), type 2 (e.g., strain Jones), type 3 (e.g., strain Dearing or strain Abney), as well as other serotypes or strains of reovirus can be used. Combinations of more than one type and/or strain of reovirus can be used, as can reovirus from different species of animal. Either solid neoplasms or hematopoietic neoplasms can be treated.

What is claimed is:  
     
         1 . A method of treating a Ras-mediated neoplasm in a mammal, comprising administering to the neoplasm a reovirus in an amount sufficient to result in reovirus-mediated oncolysis of cells of the neoplasm.  
     
     
         2 . The method of  claim 1 , wherein the reovirus is a human reovirus.  
     
     
         3 . The method of  claim 2 , wherein the reovirus is type 1.  
     
     
         4 . The method of  claim 2 , wherein the reovirus is type 2.  
     
     
         5 . The method of  claim 2 , wherein the reovirus is type 3.  
     
     
         6 . The method of  claim 1 , wherein the reovirus is a non-human reovirus.  
     
     
         7 . The method of  claim 6 , wherein the reovirus is a mammalian reovirus.  
     
     
         8 . The method of  claim 6 , wherein the reovirus is an avian reovirus.  
     
     
         9 . The method of  claim 1 , wherein more than one type of reovirus is administered.  
     
     
         10 . The method of  claim 1 , wherein more than one strain of reovirus is administered.  
     
     
         11 . The method of  claim 1 , wherein the reovirus is a field isolate.  
     
     
         12 . The method of  claim 1 , wherein the reovirus is treated with a protease prior to administration.  
     
     
         13 . The method of  claim 1 , wherein the neoplasm is a solid neoplasm.  
     
     
         14 . The method of  claim 3 , wherein the reovirus is administered by injection into the solid neoplasm.  
     
     
         15 . The method of  claim 13 , wherein the reovirus is administered intravenously into the mammal.  
     
     
         16 . The method of  claim 1 , wherein the neoplasm is a hematopoietic neoplasm.  
     
     
         17 . The method of  claim 16 , wherein the reovirus is administered intravenously into the mammal.  
     
     
         18 . The method of  claim 16 , wherein the reovirus is administered intraperitoneally into the mammal.  
     
     
         19 . The method of  claim 1 , wherein the mammal is selected from the group consisting of: mice, dogs, cats, sheep, goats, cows, horses, pigs, and non-human primates.  
     
     
         20 . The method of  claim 1 , wherein the mammal is a human.  
     
     
         21 . The method of  claim 1 , wherein the neoplasm is pancreatic cancer.  
     
     
         22 . The method of  claim 1 , wherein the neoplasm is breast cancer.  
     
     
         23 . The method of  claim 1 , wherein the neoplasm is brain cancer.  
     
     
         24 . The method of  claim 1 , wherein the neoplasm is selected from the group consisting of: lung cancer, prostate cancer, colorectal cancer, thyroid cancer, renal cancer, adrenal cancer, liver cancer, and leukemia.  
     
     
         25 . The method of  claim 1 , wherein approximately 10 3  to 10 12  plaque forming units of reovirus are administered.  
     
     
         26 . The method of  claim 1 , wherein the reovirus is administered in a single dose.  
     
     
         27 . The method of  claim 1 , wherein the reovirus is administered in more than one dose.  
     
     
         28 . The method of  claim 1 , wherein the reovirus is administered to more than one neoplasm in the mammal.  
     
     
         29 . The method of  claim 1 , wherein the ras-mediated neoplasm is metastatic.  
     
     
         30 . The method of  claim 29 , wherein the reovirus is administered to a single solid neoplasm.  
     
     
         31 . The method of  claim 29 , wherein the reovirus is administered intravenously.  
     
     
         32 . A method of treating a Ras-mediated neoplasm in a human, comprising administering to the neoplasm a reovirus in an amount sufficient to result in reovirus-mediated oncolysis of cells of the neoplasm.  
     
     
         33 . The method of  claim 32 , wherein the neoplasm is a solid neoplasm.  
     
     
         34 . The method of  claim 33 , wherein the solid neoplasm is pancreatic cancer.  
     
     
         35 . The method of  claim 33 , wherein the reovirus is administered by injection into the solid neoplasm.