Viral vectors and their use in therapeutic methods
The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.
1. A method of treating cancer of the nervous system in a patient, said method comprising administering to a patient having cancer of the nervous system a herpes simplex virus-1, wherein said herpes simplex virus-1 comprises:
an inactivating mutation in the ICP47 locus of said virus, wherein said mutation occurs between the BstEII site and the EcoNI site of the BamHI fragment encompassing the ICP47 region, and said mutation places US11 under control of the ICP47 immediate-early promoter that results in early expression of US11;
an inactivating mutation in the γ34.5 neurovirulence locus of said virus; and
an inactivating mutation in the ICP6 locus of said virus.
2. The method of claim 1 , wherein the patient has or is at risk of developing one or more metastases.
3. The method of claim 1 , wherein said herpes simplex virus-1 is administered to a tumor of said patient.
4. The method of claim 1 , wherein said herpes simplex virus-1 is administered parenterally to said patient.
5. The method of claim 1 , wherein said herpes simplex virus-1 further comprises sequences encoding a heterologous gene product.
6. The method of claim 5 , wherein said heterologous gene product comprises a vaccine antigen or an immunomodulatory protein.
7. The method of claim 6 , wherein said immunomodulatory protein is selected from the group consisting of a cytokine, a chemokine, RANTES, a macrophage inflammatory peptide, a complement component or receptor, an immune system accessory molecules, an adhesion molecule, and an adhesion receptor molecule.
8. The method of claim 7 , wherein said cytokine is selected from the group consisting of an interleukin, tumor necrosis factor, granulocyte macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), and granulocyte colony stimulating factor (G-CSF).
9. The method of claim 1 , wherein said cancer of the nervous system is selected from the group consisting of astrocytoma, oligodendroglioma, meningioma, neurofibroma, glioblastoma, ependymoma, Schwannoma, neurofibrosarcoma, and neuroblastoma.
10. The method of claim 1 , wherein said cancer of the nervous system is astrocytoma.
11. The method of claim 1 , wherein said cancer of the nervous system is oligodendroglioma.
12. The method of claim 1 , wherein said cancer of the nervous system is meningioma.
13. The method of claim 1 , wherein said cancer of the nervous system is neurofibroma.
14. The method of claim 1 , wherein said cancer of the nervous system is glioblastoma.
15. The method of claim 1 , wherein said cancer of the nervous system is ependymoma.
16. The method of claim 1 , wherein said cancer of the nervous system is Schwannoma.
17. The method of claim 1 , wherein said cancer of the nervous system is neurofibrosarcoma.
18. The method of claim 1 , wherein said cancer of the nervous system is neuroblastoma.
19. The method of claim 7 , wherein said cytokine is granulocyte macrophage colony stimulating factor (GM-CSF).