Systemic treatment of metastatic and/or systemically-disseminated cancers using GM-CSF-expressing poxviruses
The present invention concerns methods and compositions for the treatment of cancer and cancer cells using intravascular administration of a vaccinia virus. In some embodiments, methods and compositions involve a replicative vaccinia virus that encodes GM-CSF.
1. A method of killing a cancer cell in a human subject comprising administering intravascularly to the subject 10 9 to 10 10 plaque forming units (Pfu) of a replicative Wyeth strain vaccinia virus JX-594.
2. The method of claim 1 , wherein the vaccinia virus is administered intravenously.
3. The method of claim 1 , wherein the vaccinia virus is administered intraarterially.
4. The method of claim 1 , wherein the vaccinia virus is in a pharmaceutically acceptable formulation.
5. The method of claim 1 , wherein the subject is administered the vaccinia virus multiple times.
6. The method of claim 5 , wherein a second treatment occurs within 3 weeks of a first treatment.
7. The method of claim 6 , wherein the second treatment occurs within 2 weeks of the first treatment.
8. The method of claim 5 , wherein the same dose is administered.
9. The method of claim 1 , wherein the administration occurs intravascularly by injection.
10. The method of claim 1 , wherein the administration occurs intravascularly using intravenous drip or bolus.
11. The method of claim 1 , wherein the administration occurs intravascularly using a pump.
12. The method of claim 1 , wherein the cancer cell is a metastasized cancer cell.
13. The method of claim 1 , wherein the subject has lung cancer, colorectal cancer, breast cancer, prostate cancer, pancreatic cancer, hepatocellular cancer, leukemia, lymphoma, myeloma or melanoma.
14. A method of treating one or more metastases in a human subject comprising administering intravascularly to the subject 10 9 to 10 10 plaque forming units (Pfu) of a replicative Wyeth strain vaccinia virus JX-594.
15. The method of claim 1 , wherein expression of a nucleic acid encoding granulocyte-macrophage colony stimulating factor (GM-CSF) is directed by a synthetic vaccinia early/late promoter.