Reovirus for the treatment of cellular proliferative disorders

Abstract

Methods for treating proliferative disorders, by administering reovirus to a Ras-mediated proliferative disorder, are disclosed. The reovirus is administered so that it ultimately directly contacts ras-mediated proliferating cells. Proliferative disorders include but are not limited to neoplasms. Human reovirus, non-human mammalian reovirus, and/or avian reovirus can be used. If the reovirus is human reovirus, serotype 1 (e.g., strain Lang), serotype 2 (e.g., strain Jones), serotype 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 - 25 . (canceled)  
   
   
       26 . A pharmaceutical composition comprising a recombinant reovirus, a chemotherapeutic agent and a pharmaceutically acceptable excipient.  
   
   
       27 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus results from reassortment of two or more strains of reovirus.  
   
   
       28 . The pharmaceutical composition of  claim 27 , wherein the two or more strains of reovirus are selected from the group consisting of strain Dearing, strain Abney, strain Jones and strain Lang.  
   
   
       29 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus results from reassortment of two reoviruses selected from the group consisting of serotype 1 reoviruses, serotype 2 reoviruses and serotype 3 reoviruses.  
   
   
       30 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus results from co-infection of mammalian cells with different subtypes of reovirus.  
   
   
       31 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus is naturally-occurring.  
   
   
       32 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus comprises different subtypes of coat proteins in the resulting virion capsid.  
   
   
       33 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus is immunoprotected.  
   
   
       34 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus is coated in a liposome or micelle.  
   
   
       35 . The pharmaceutical composition of  claim 26 , wherein the recombinant reovirus comprises mutated coat proteins.  
   
   
       36 . The pharmaceutical composition of  claim 26 , wherein the chemotherapeutic agent is not BCNU.  
   
   
       37 . The pharmaceutical composition of  claim 26 , wherein the chemotherapeutic agent is selected from the group consisting of 5-fluorouracil, mitomycin C, methotrexate, hydroxyurea, cyclophosphamide, dacarbazine, mitoxantrone, doxorubicin, epirubicin, herceptin, etopside, pregnasome, carboplatin, cisplatin, taxol, taxotere, tamoxifen, interferon, an aromatase inhibitor and an LHRH analog.  
   
   
       38 . A pharmaceutical composition comprising a modified reovirus, a chemotherapeutic agent and a pharmaceutically acceptable excipient.  
   
   
       39 . The pharmaceutical composition of  claim 38 , wherein the modified reovirus is chemically or biochemically pretreated with a protease.  
   
   
       40 . The pharmaceutical composition of  claim 38 , wherein the modified reovirus is coated in a liposome or micelle.  
   
   
       41 . The pharmaceutical composition of  claim 38 , wherein the modified reovirus comprises mutated coat proteins.  
   
   
       42 . The pharmaceutical composition of  claim 38 , where the modified reovirus has reduced immunogenecity as compared to wild type reovirus.  
   
   
       43 . The pharmaceutical composition of  claim 38 , wherein the outer capsid of the modified reovirus has been removed.  
   
   
       44 . The pharmaceutical composition of  claim 38 , wherein the chemotherapeutic agent is not BCNU.  
   
   
       45 . The pharmaceutical composition of  claim 38 , wherein the chemotherapeutic agent is selected from the group consisting of 5-fluorouracil, mitomycin C, methotrrexate, hydroxyurea, cyclophosphamide, dacarbazine, mitoxantrone, doxorubicin, epirubicin, herceptin, etopside, pregnasome, carboplatin, cisplatin, taxol, taxotere, tamoxifen, inferferon, an aromatase inhibitor and an LHRH analog.  
   
   
       46 . A kit comprising a pharmaceutical composition comprising a recombinant reovirus, a chemotherapeutic agent and a pharmaceutically acceptable excipient.  
   
   
       47 . The kit of  claim 46 , wherein the recombinant reovirus results from reassortment of two or more strains of reovirus.  
   
   
       48 . A kit comprising a pharmaceutical composition comprising a modified reovirus, a chemotherapeutic agent and a pharmaceutically acceptable excipient.  
   
   
       49 . The kit of  claim 48 , where the modified reovirus has reduced immunogenecity as compared to wild type reovirus.