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.

1 .- 35 . (canceled) 
   
   
       36 . A method of treating a neoplasm in a mammal, comprising administering to the mammal with the neoplasm a reovirus, wherein the neoplasm comprises cells in which an element of the ras-signaling pathway is activated, and wherein the reovirus is administered in an amount sufficient to result in oncolysis of the cells of the neoplasm. 
   
   
       37 . The method of  claim 36 , wherein the reovirus is a human reovirus. 
   
   
       38 . The method of  claim 36 , wherein the reovirus is selected from the group consisting of type 1 reovirus, type 2 reovirus and type 3 reovirus. 
   
   
       39 . The method of  claim 36 , wherein the reovirus is administered in a single dose. 
   
   
       40 . The method of  claim 36 , wherein the reovirus is administered in more than one dose. 
   
   
       41 . The method of  claim 36 , wherein more than one type or more than one strain of reovirus is administered. 
   
   
       42 . The method of  claim 36 , wherein approximately 10 3  to 10 12  plaque forming units of reovirus are administered. 
   
   
       43 . The method of  claim 36 , wherein the neoplasm is a solid neoplasm and wherein the reovirus is administered by injection into the solid neoplasm. 
   
   
       44 . The method of  claim 36 , wherein the reovirus is administered intravenously. 
   
   
       45 . A method of treating a neoplasm in a mammal, comprising administering to the mammal with the neoplasm a reovirus, wherein the neoplasm comprises cells in which PKR is inactivated or deleted, and wherein the reovirus is administered in an amount sufficient to result in oncolysis of the cells of the neoplasm. 
   
   
       46 . The method of  claim 45 , wherein the reovirus is a human reovirus. 
   
   
       47 . The method of  claim 45 , wherein the reovirus is selected from the group consisting of type 1 reovirus, type 2 reovirus and type 3 reovirus. 
   
   
       48 . The method of  claim 45 , wherein the reovirus is administered in a single dose. 
   
   
       49 . The method of  claim 45 , wherein the reovirus is administered in more than one dose. 
   
   
       50 . The method of  claim 45 , wherein more than one type or more than one strain of reovirus is administered. 
   
   
       51 . The method of  claim 45 , wherein approximately 10 3  to 10 12  plaque forming units of reovirus are administered. 
   
   
       52 . The method of  claim 45 , wherein the neoplasm is a solid neoplasm and wherein the reovirus is administered by injection into the solid neoplasm. 
   
   
       53 . The method of  claim 45 , wherein the reovirus is administered intravenously. 
   
   
       54 . A method of treating a neoplasm in a mammal, comprising administering to the mammal with the neoplasm a reovirus, wherein the neoplasm comprises cells in which PKR is not activated upon exposure to the reovirus, and wherein the reovirus is administered in an amount sufficient to result in oncolysis of the cells of the neoplasm. 
   
   
       55 . The method of  claim 54 , wherein the reovirus is a human reovirus. 
   
   
       56 . The method of  claim 54 , wherein the reovirus is selected from the group consisting of type 1 reovirus, type 2 reovirus and type 3 reovirus. 
   
   
       57 . The method of  claim 54 , wherein the reovirus is administered in a single dose. 
   
   
       58 . The method of  claim 54 , wherein the reovirus is administered in more than one dose. 
   
   
       59 . The method of  claim 54 , wherein more than one type or more than one strain of reovirus is administered. 
   
   
       60 . The method of  claim 54 , wherein approximately 10 3  to 10 12  plaque forming units of reovirus are administered. 
   
   
       61 . The method of  claim 54 , wherein the neoplasm is a solid neoplasm and wherein the reovirus is administered by injection into the solid neoplasm. 
   
   
       62 . The method of  claim 54 , wherein the reovirus is administered intravenously. 
   
   
       63 . A method of treating a neoplasm in a mammal, comprising administering to the mammal with the neoplasm a reovirus, wherein the neoplasm comprises cells in which phosphorylation of PKR is prevented, and wherein the reovirus is administered in an amount sufficient to result in oncolysis of the cells of the neoplasm. 
   
   
       64 . The method of  claim 63 , wherein the reovirus is a human reovirus. 
   
   
       65 . The method of  claim 63 , wherein the reovirus is selected from the group consisting of type 1 reovirus, type 2 reovirus and type 3 reovirus. 
   
   
       66 . The method of  claim 63 , wherein the reovirus is administered in a single dose. 
   
   
       67 . The method of  claim 63 , wherein the reovirus is administered in more than one dose. 
   
   
       68 . The method of  claim 63 , wherein more than one type or more than one strain of reovirus is administered. 
   
   
       69 . The method of  claim 63 , wherein approximately 10 3  to 10 12  plaque forming units of reovirus are administered. 
   
   
       70 . The method of  claim 63 , wherein the neoplasm is a solid neoplasm and wherein the reovirus is administered by injection into the solid neoplasm. 
   
   
       71 . The method of  claim 63 , wherein the reovirus is administered intravenously. 
   
   
       72 . A method of treating a neoplasm in a mammal, comprising administering to the mammal with the neoplasm a reovirus, wherein the neoplasm comprises EGFR-transformed cells, and wherein the reovirus is administered in an amount sufficient to result in oncolysis of the cells of the neoplasm. 
   
   
       73 . The method of  claim 72 , wherein the reovirus is a human reovirus. 
   
   
       74 . The method of  claim 72 , wherein the reovirus is selected from the group consisting of type 1 reovirus, type 2 reovirus and type 3 reovirus. 
   
   
       75 . The method of  claim 72 , wherein the reovirus is administered in a single dose. 
   
   
       76 . The method of  claim 72 , wherein the reovirus is administered in more than one dose. 
   
   
       77 . The method of  claim 72 , wherein more than one type or more than one strain of reovirus is administered. 
   
   
       78 . The method of  claim 72 , wherein approximately 10 3  to 10 12  plaque forming units of reovirus are administered. 
   
   
       79 . The method of  claim 72 , wherein the neoplasm is a solid neoplasm and wherein the reovirus is administered by injection into the solid neoplasm. 
   
   
       80 . The method of  claim 72 , wherein the reovirus is administered intravenously.