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 subject previously administered a Wyeth strain vaccinia virus lacking a functional thymidine kinase gene and expressing GM-CSF comprising administering an effective amount of an anti-angiogenic tyrosine kinase inhibitor at least 1 week and up to 13 weeks after the vaccinia virus therapy, wherein the anti-angiogenic tyrosine kinase inhibitor is sorafenib or sunitinib.
2. The method of claim 1 , wherein the anti-angiogenic tyrosine kinase inhibitor 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 anti-angiogenic tyrosine kinase inhibitor is administered at least 5, 6, 7, or 8 weeks 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 cancer is 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.
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 JX-594.
14. The method of claim 1 , wherein the anti-angiogenic kinase inhibitor is administered at least 2 weeks after the vaccinia virus administration.
15. The method of claim 3 , wherein the non-invasive imaging is contrast enhanced CT scanning.