Methods and compositions for treatment of hematologic cancers

Abstract

The present invention relates to oncolytic Picornaviruses and methods and compositions for treating subjects having hematologic cancers. These include methods and compositions for treatment of myeloma, using disclosed Picornavirus such as Coxsackievirus, in methods of direct or indirect administration to subjects and ex vivo purging of malignant cells within auto grafts prior to transplantation.

What is claimed is: 
     
         1 . A method for treating and/or preventing hematologic cancer in a subject, the method comprising administering a therapeutically effective amount of a Picornavirus or a modified form thereof such that at least some cells of the cancer undergo viral oncolysis. 
     
     
         2 . The method according to  claim 1 , wherein the Picornavirus is selected from the group consisting of prototype and clinically isolated strains of enteroviruses including Coxsackievirus, Echovirus, Poliovirus, unclassified enteroviruses, Rhinovirus, Paraechovirus, Hepatovirus, and Cardiovirus. 
     
     
         3 . The method according to  claim 1 , wherein the Picornavirus is a Coxsackie A group virus selected from the group consisting of CVA13, CVA15, CVA18, CVA20, CVA21, modified forms thereof, and combinations thereof. 
     
     
         4 . The method according to  claim 1 , wherein the Picornavirus is administered intravenously, intratumorally, intraperitoneally, intramuscularly, ex vivo purging of malignant cells within auto grafts prior to autologous stem cell transplantation, or by ex vivo purging of malignant cells within auto grafts prior to transplantation. 
     
     
         5 . The method according to  claim 4 , wherein the auto grafts comprise hematopoietic stem cells. 
     
     
         6 . The method according to  claim 1 , wherein the range of viral dose is between about 0.01 to about 1000 infectious viral units per cell. 
     
     
         7 . The method according to  claim 1 , wherein the virus is administered to a subject in combination with an effective amount of a chemotherapeutic agent. 
     
     
         8 . The method according to  claim 1 , wherein the virus is administered to a subject in combination with an effective amount of a probiotic agent. 
     
     
         9 . The method according to  claim 1 , wherein the hematologic cancer is a cancer selected from the group consisting of multiple myeloma, B cell lymphoma, B prolymphocytic leukemia and monocytic leukemia. 
     
     
         10 . The method according to  claim 1 , wherein cells of the hematologic cancer over-express the virus-cell entry receptor molecules intercellular adhesion molecule-1 (ICAM-1) and/or decay-accelerating factor (DAF). 
     
     
         11 . The method according to  claim 1 , wherein cells of the hematologic cancer constitutively express NF- K B. 
     
     
         12 . A method for treating and/or preventing a hematologic cancer selected from the group consisting of multiple myeloma, B cell lymphoma, B prolymphocytic leukemia and monocytic leukemia, in a subject, the method comprising administering a therapeutically effective amount of a Picornavirus selected from the group consisting of CVA13, CVA15, CVA18 and CVA21 or a combination thereof such that at least some cells of the cancer undergo viral oncolysis. 
     
     
         13 . A method for treating and/or preventing hematologic cancer in a subject, the method comprising administering a therapeutically effective amount of a nucleic acid molecule derived from a Picornavirus or a modified form thereof such that at least some cells of the cancer are killed by the virus, 
     
     
         14 . The method according to  claim 13 , wherein the Picornavirus is a Coxsackie A group virus selected from the group consisting of CVA13, CVA15, CVA18, CVA20, CVA21. 
     
     
         15 . The method according to  claim 1  or  13 , wherein the subject is a human. 
     
     
         16 . A pharmaceutical composition for use in treating and/or preventing hematologic cancer in a subject, the composition comprising an effective amount of a Picornavirus or a modified form thereof, capable of lyrically infecting a hematologic cancer, together with a pharmaceutically acceptable excipient, diluent or carrier. 
     
     
         17 . A pharmaceutical composition for use in treating and/or preventing hematologic cancer in a subject, the composition comprising an effective amount of a nucleic acid molecule derived from a Picornavirus or a modified form thereof, capable of lyrically infecting a hematologic cancer, together with a pharmaceutically acceptable excipient, diluent or carrier. 
     
     
         18 . Use of a Picornavirus or a modified form thereof, capable of lyrically infecting a hematologic cancer, in the manufacture of a medicament for treating and/or preventing hematologic cancer in a subject. 
     
     
         19 . The use according to  claim 18 , wherein the Picornavirus is a Coxsackie A group virus selected from the group consisting of CVA13, CVA15, CVA18, CVA20, CVA21. 
     
     
         20 . The use according to  claim 18 , wherein the hematologic cancer is a cancer selected from the group consisting of multiple myeloma, B cell lymphoma, B prolymphocytic leukemia and monocytic leukemia. 
     
     
         21 . Use of a nucleic acid molecule derived from a Picornavirus or a modified form thereof, capable of lyrically infecting a hematologic cancer, in the manufacture of a medicament for treating and/or preventing hematologic cancer in a subject. 
     
     
         22 . A method for inducing an immune response in a subject against hematologic tumor or cancer cells, the method comprising infecting said cells of the subject with a therapeutically effective amount of a Picornavirus or a modified form thereof such that at least some cells of the cancer undergo viral oncolysis.