Oncolytic vaccinia virus combination cancer therapy
Embodiments of the invention are directed methods that include a thymidine kinase deficient vaccinia virus. The methods include evaluating a tumor for reperfusion after treatment with vaccinia virus and administering an anti-angiogenic agent if reperfusion is detected.
1. A method for treating cancer in a human subject previously administered a vaccinia virus lacking a thymidine kinase gene and expressing GM-CSF comprising administering to the subject an effective amount of an anti-angiogenic agent that inhibits VEGF-R tyrosine kinase, wherein the inhibitor of VEGF-R tyrosine kinase is administered up to 13 weeks after the vaccinia virus therapy.
2. The method of claim 1 , wherein the inhibitor of VEGF-R tyrosine kinase is administered after determining whether a tumor is undergoing re-vascularization.
3. The method of claim 2 , wherein determining tumor re-vascularization is by non-invasive imaging of the tumor.
4. The method of claim 3 , wherein the non-invasive imaging is magnetic resonance imaging (MRI).
5. The method of claim 4 , wherein the magnetic resonance imaging is dynamic contrast-enhanced MRI (dce-MRI).
6. The method of claim 1 , wherein the inhibitor of VEGF-R tyrosine kinase is administered at least 1 week after the vaccinia virus administration.
7. The method of claim 1 , wherein the cancer is a brain tumor, a head & neck cancer tumor, an esophageal tumor, a skin tumor, a lung tumor, a thymic tumor, a stomach tumor, a colon tumor, a liver tumor, an ovarian tumor, a uterine tumor, a bladder tumor, a testicular tumor, a rectal tumor, a breast tumor, a kidney tumor, a pancreatic tumor, hepatocellular carcinoma or a renal carcinoma.
8. The method of claim 7 , wherein the tumor is a pancreatic tumor, a hepatocellular carcinoma or a renal carcinoma.
9. The method of claim 7 wherein the tumor is a metastasis.
10. The method of claim 9 , wherein the metastasis is colon or renal metastasis.
11. The method of claim 1 , further comprising first administering to the subject the vaccinia virus therapy.
12. The method of claim 11 , wherein the vaccinia virus is administered intratumorally, intravascularly, or both intravascularly and intratumorally.
13. The method of claim 1 , wherein the vaccinia virus is a Wyeth strain.
14. The method of claim 13 , wherein the vaccinia virus is JX-594.
15. The method of claim 1 , wherein the inhibitor of VEGF-R tyrosine kinase is administered at least 2 weeks after the vaccinia virus administration.
16. The method of claim 1 , wherein the inhibitor of VEGF-R tyrosine kinase is selected from the group consisting of: SU5416, SU6668, vatalanib, AEE788, ZD6474, ZD4190, AZD2171, GW786034, CP-547,632, AG013736, and YM-359445.
17. The method of claim 3 , wherein the non-invasive imaging is contrast enhanced CT scanning.
18. The method of claim 1 , wherein the cancer has failed to respond favorably to or is resistant to treatment with one or more chemotherapeutic agents.
19. The method of claim 18 , wherein the treatment with one or more chemotherapeutic agents comprises administering one or more anti-angiogenic agents.
20. The method of claim 1 , wherein the vaccinia virus is administered by intratumoral injection every two weeks.
21. A method for treating cancer in a human subject previously administered a vaccinia virus lacking a thymidine kinase gene and expressing GM-CSF comprising administering to the subject an effective amount of sorafenib, sutent or AG013736 up to 13 weeks after the vaccinia virus therapy.
22. The method of claim 21 , wherein the cancer is a pancreatic tumor, a hepatocellular carcinoma or a renal carcinoma.