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 - 21 . (canceled) 
     
     
         22 . A method for inhibiting a human cancer cell, comprising contacting a human cancer cell that is deficient in an innate antiviral response and permissive to Myxoma virus replication with an effective amount of a mutated Myxoma virus comprising a mutated M135R gene, wherein the mutated M135R gene comprises a mutation in a coding region or a regulatory region of the M135R gene such that the mutated M135R gene does not express a functional M135R protein. 
     
     
         23 . The method of  claim 22 , wherein the innate antiviral response comprises interferon signaling. 
     
     
         24 . The method of  claim 22 , wherein the mutated M135R gene comprises a mutation in a coding region of the M135R gene, and wherein the mutation is a deletion, replacement, or interruption of the coding region or a segment thereof. 
     
     
         25 . The method of  claim 24 , wherein the mutation is a deletion or replacement of part or all of the coding region of the M135R gene. 
     
     
         26 . The method of  claim 22 , wherein the mutated M135R gene comprises a mutation in the regulatory region of the M135R gene, and wherein the mutation is a deletion, replacement, or interruption of the regulatory region or a segment thereof. 
     
     
         27 . The method of claim of  claim 26 , wherein the mutation is a deletion or replacement of part or all of the regulatory region of the M135R gene. 
     
     
         28 . The method of  claim 22 , wherein the contacting step comprises administering the mutated Myxoma virus to a human cancer patient having cancer cells that are deficient in an innate antiviral response and permissive to Myxoma virus replication. 
     
     
         29 . The method of  claim 28 , wherein the cancer is selected from the group consisting of prostate cancer, renal cancer, colon cancer, lung cancer, ovarian cancer, melanoma, breast cancer, and osteosarcoma. 
     
     
         30 . The method of  claim 28 , wherein the mutated Myxoma virus is further modified genetically to express a therapeutic protein. 
     
     
         31 . The method of  claim 28 , wherein the mutated Myxoma virus is administered to the site of the cancer by injection. 
     
     
         32 . The method of  claim 28 , wherein the human cancer patient is further administered an anti-cancer agent. 
     
     
         33 . The method of  claim 28 , wherein part or all of the open reading frame that encodes M135R of the mutated Myxoma virus is deleted. 
     
     
         34 . A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a mutated Myxoma virus, which comprises a mutated M135R gene, wherein (i) part or all of the open reading frame of the M135R gene is deleted or replaced, or (ii) part or all of the regulatory region of the M135R gene is deleted or replaced. 
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the mutated Myxoma virus is further modified genetically to express a therapeutic protein. 
     
     
         36 . The pharmaceutical composition of  claim 34 , wherein the pharmaceutical composition further comprises a therapeutic agent. 
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the therapeutic agent is rapamycin. 
     
     
         38 . A method for producing a mutated Myxoma virus that does not express functional M135R protein, the method comprising: deleting or replacing part or whole of (i) the coding region of a M135R gene, or (ii) the regulatory region of the M135R gene to produce a mutated Myxoma virus. 
     
     
         39 . The method of  claim 38 , wherein the method further comprises confirming that the mutated Myxoma virus does not express a functional M135R protein. 
     
     
         40 . The method of  claim 39 , wherein the method further comprises contacting the mutated Myxoma virus with a human cancer cell to determine infectivity and/or cytolytic effects on the human cancer cell.