Methods of treating and detecting cancer using viruses
The invention provides a method of treating cancer in a mammal comprising administering to the mammal an effective amount of virus, particularly Newcastle Disease Virus or other Paramyxovirus. The invention also provides a method of treating cancer in a mammal comprising administering such viruses to the mammal in combination with another agent such as a chemotherapeutic compound, immunoadjuvant, cytokine, or immunosuppressive agent. The invention further provides a method of detecting cancer cells in a mammal using Paramyxovirus as an imaging agent and as an indicator of cancer cell growth in the mammal. The invention further provides genetically engineered Paramyxoviruses, and kits containing the viral compositions disclosed by the invention.
1. A method of treating cancer in a mammal having a tumor comprising administering intravenously to said mammal more than one dose of a pharmaceutical composition comprising live purified Newcastle Disease Virus in an amount sufficient to cause tumor regression.
2. The method of claim 1 , wherein said tumor is selected from the group consisting of lung carcinoma, breast carcinoma, prostate carcinoma, colon adenocarcinoma, cervical carcinoma, endometrial carcinoma, ovarian carcinoma, bladder carcinoma, Wilm's tumor, fibrosarcoma, osteosarcoma, melanoma, synovial sarcoma, neuroblastoma and glioblastoma.
3. The method of claim 1 , wherein said tumor is colon adenocarcinoma.
4. The method of claim 1 , wherein said tumor is melanoma.
5. The method of claim 1 , wherein said tumor is neuroblastoma.
6. The method of claim 1 , wherein said live purified Newcastle Disease Virus is strain Mass MK107.
7. The method of claim 1 , wherein said live purified Newcastle Disease Virus is strain 73-T.
8. The method of claim 1 , wherein the amount of live purified Newcastle Disease Virus administered intravenously is about 4×10 10 to 4×10 12 PFU/kg.
9. The method of claim 1 , wherein the live purified Newcastle Disease Virus is administered intravenously in an amount of about 10 8 PFU.
10. The method of claim 1 , further comprising administering a chemotherapeutic agent.
11. The method of claim 10 , wherein the chemotherapeutic agent is selected from the group consisting of thiotepa, busulfan, cyclophosphamide, methotrexate, cytarabine, bleomycin, cisplatin, doxorubicin, melphalan, mercaptopurine, vinblastine, 5-fluorouracil, paclitaxel and retinoic acid.
12. The method of claim 11 , wherein the chemotherapeutic agent is 5-fluorouracil.
13. The method of claim 1 , further comprising administering an immunosuppressive agent.
14. The method of claim 13 , wherein said immunosuppressive agent is a corticosteroid.
15. The method of claim 1 , further comprising administering a cytotoxic or cytostatic agent.
16. The method of claim 15 , wherein said cytotoxic or cytostatic agent is an antibody.
17. The method of claim 15 , wherein said cytotoxic or cytostatic agent is a cytokine.
18. The method of claim 1 , wherein said live purified Newcastle Disease Virus is purified from cell culture.
19. The method of claim 1 , wherein said tumor is cervical carcinoma.
20. The method of claim 1 , wherein said pharmaceutical composition consists essentially of live purified Newcastle Disease Virus.
21. The method of claim 1 , wherein said pharmaceutical composition also comprises a pharmaceutically acceptable carrier.
22. The method of claim 1 , wherein said tumor is a human tumor.
23. The method of claim 1 , wherein said tumor is greater than 0.6 cm in diameter.
24. The method of claim 1 , wherein said tumor is a metastatic tumor.
25. The method of claim 1 , wherein said amount administered is sufficient to cause complete tumor regression.
26. The method of claim 1 , further comprising administering radiation.
27. The method of claim 1 , wherein said method results in tumor regression.