Oncolytic virus
The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR−/−, STAT1−/− or both PKR−/− and STAT1−/−. The virus is selected from the group consisting of Rhabdovirus and picornavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.
1. A method of reducing the viability of a tumor cell, comprising administering to the tumor cell a virus, such that the virus is delivered to the tumor cell,
wherein said virus is a vesicular stomatitis virus and said tumor cell is a hematopoietic tumor cell and
wherein the virus is contained in a cell infected with the virus and the administering comprises administering the virus-infected cell.
2. The method of claim 1 , wherein the hematopoietic tumor cell is a leukemia, a lymphoma, or a myeloma.
3. The method of claim 1 , wherein the hematopoietic tumor cell is a leukemia.
4. The method of claim 3 , wherein the leukemia is acute myelogenous leukemia.
5. The method of claim 3 , wherein the leukemia is chronic myelogenous leukemia.
6. The method of claim 3 , wherein the leukemia is promyelocytic leukemia.
7. The method of claim 3 , wherein the leukemia is T cell leukemia.
8. The method of claim 1 , wherein the hematopoietic tumor cell is a lymphoma.
9. The method of claim 1 , wherein the hematopoietic tumor cell is a myeloma.
10. The method of claim 1 , wherein the tumor cell is PKR−/−; STAT1−/−; or both PKR−/− and STAT1−/−.
11. The method of claim 1 , further comprising administering interferon to the tumor cell prior to administering VSV, such that the interferon is delivered to the tumor cell.
12. The method of claim 1 , wherein the virus is unable to inactivate PKR activity within the tumor cell.
13. The method of claim 1 , wherein the virus is an attenuated strain of vesicular stomatitis virus.
14. The method of claim 1 , wherein the virus is vesicular stomatitis virus strain M1.
15. The method of claim 1 , wherein the virus is vesicular stomatitis virus strain M2.
16. The method claim 1 , wherein the virus is vesicular stomatitis virus strain M3.
17. The method of claim 1 , wherein the virus is vesicular stomatitis virus strain M4.
18. The method of claim 1 , wherein the virus is vesicular stomatitis virus strain M5.
19. The method of claim 1 , wherein the tumor cell is in a mammalian subject.
20. The method of claim 19 , wherein the mammalian subject is a non-human mammal.
21. The method of claim 19 , further comprising treating the mammalian subject with an interferon.
22. The method of claim 19 , wherein the mammalian subject is a human.
23. The method of claim 19 , wherein the administering comprises administering the virus-infected cell to the subject by a route selected from intratumorally, intravenously and intraperitoneally.
24. A method of reducing the viability of a tumor cell within a population of cells comprising administering a vesicular stomatitis virus to the population of cells, such that the virus is delivered to the population of cells,
wherein the virus is contained in a cell infected with the virus and the administering comprises administering the virus-infected cell,
wherein the population of cells comprises hematopoietic tumor cells and non-tumor cells and
wherein the virus is able to selectively reduce the viability of the hematopoietic tumor cells.
25. The method of claim 24 , wherein the virus is unable to inactivate PKR activity in the tumor cell.
26. The method of claim 25 , further comprising treating the population of cells with interferon prior to administering the virus.
27. The method of claim 24 , wherein the hematopoietic tumor cells are leukemia cells.
28. The method of claim 27 , wherein the leukemia cells are acute myelogenous leukemia cells.
29. The method of claim 27 , wherein the leukemia cells are chronic myelogenous leukemia cells.
30. The method of claim 27 , wherein the leukemia cells are promyelocytic leukemia cells.
31. The method of claim 27 , wherein the leukemia cells are T cell leukemia cells.
32. The method of claim 24 , wherein the hematopoietic tumor cells are lymphoma cells.
33. The method of claim 24 , wherein the hematopoietic tumor cells are myeloma cells.
34. The method of claim 24 , wherein the tumor cells are PKR−/−; STAT1−/−; or both PKR−/− and STAT1−/−.
35. The method of claim 24 , wherein the virus is an attenuated strain of vesicular stomatitis virus.
36. The method of claim 24 , wherein the virus is vesicular stomatitis virus strain M1.
37. The method of claim 24 , wherein the virus is vesicular stomatitis virus strain M2.
38. The method of claim 24 , wherein the virus is vesicular stomatitis virus strain M3.
39. The method of claim 24 , wherein the virus is vesicular stomatitis virus strain M4.
40. The method of claim 24 , wherein the virus is vesicular stomatitis virus strain M5.
41. The method of claim 24 , wherein the administering of the vesicular stomatitis virus to the population of cells is performed in vitro.