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 cancer in a subject comprising administering to the subject an attenuated Western Reserve strain vaccinia virus comprising a mutation in a gene encoding an interferon modulating polypeptide selected from B8R and B18R that results in the virus having a reduced ability to inhibit an antiviral response mediated by an interferon.
2. The method of claim 1 , wherein the virus comprises a mutation in the gene encoding B8R.
3. The method of claim 1 , wherein the vaccinia virus comprises a mutation in the gene encoding B18R.
4. The method of claim 1 , wherein the cancer is selected from the group consisting of bladder, blood, bone, bone marrow, brain, breast, colorectal, esophagus, gastrointestinal, head and neck, kidney, liver, lung, nasopharynx, neck, ovary, pancreas, prostate, stomach, skin, testicular, tongue, or uterus cancer.
5. The method of claim 1 , wherein the cancer is colorectal or prostate cancer.
6. The method of claim 1 , wherein the mutation results in the virus lacking a functional B8R or B18R polypeptide.
7. The method of claim 6 , wherein the mutation is an insertion or deletion.
8. The method of claim 1 , wherein the vaccinia virus further comprises a nucleic acid sequence encoding a heterologous therapeutic polypeptide.
9. The method of claim 1 , wherein the subject is a human.
10. A method for treating cancer in a subject comprising administering to the subject an attenuated vaccinia virus comprising a mutation in a gene encoding B8R and a mutation in a gene encoding B18R said mutations resulting in the virus having a reduced ability to inhibit an antiviral response mediated by an interferon.
11. The method of claim 10 wherein the cancer is selected from the group consisting of bladder, blood, bone, bone marrow, brain, breast, colorectal, esophagus, gastrointestinal, head and neck, kidney, liver, lung, nasopharynx, neck, ovary, pancreas, prostate, stomach, skin, testicular, tongue, or uterus cancer.
12. The method of claim 11 , wherein the cancer is colorectal or prostate cancer.
13. The method of claim 10 , wherein the vaccinia virus further comprises a nucleic acid sequence encoding a heterologous therapeutic polypeptide.
14. The method of claim 10 , wherein the subject is a human.