Methods and compositions concerning poxviruses and cancer
The present invention concerns methods and compositions for the treatment of cancer and cancer cells using altered poxviruses, including a vaccinia virus that has been altered to generate a more effective therapeutic agent. Such poxviruses are engineered to be attenuated or weakened in their ability to affect normal cells. In some embodiments, methods and compositions involve poxviruses that possess mutations that result in poxviruses with diminished or eliminated capability to implement an antiviral response in a host. Poxviruses with these mutations in combination with other mutations can be employed for more effective treatment of cancer.
1. A method for treating a cancerous tumor in a subject comprising administering to the subject an effective amount of a vaccinia virus encoding an A34R polypeptide comprising a K151E substitution that results in increased production of an extracellular enveloped virus (EEV) form of the vaccinia virus.
2. The method of claim 1 , wherein the vaccinia virus lacks at least one interferon-modulating polypeptide selected from B18R, B8R, B13R, vC12L, A53R or E3L.
3. The method of claim 1 , wherein the vaccinia virus is Copenhagen or Western Reserve strain.
4. The method of claim 1 , wherein the virus lacks at least one functional complement control polypeptide.
5. The method of claim 1 , wherein the virus lacks at least one functional TNF-modulating polypeptide.
6. The method of claim 1 , wherein the virus lacks at least one functional serine protease inhibitor.
7. The method of claim 1 , wherein the virus lacks at least one functional IL-1β modulator.
8. The method of claim 1 , wherein the virus is administered intravascularly.
9. The method of claim 1 , wherein the subject is a human.