Use of a combination of Myxoma virus and rapamycin for therapeutic treatment
The present invention relates to therapeutic use of a combination of Myxoma virus, including in combination with rapamycin. Treatment with rapamycin enhances the ability of Myxoma virus to selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon. The combination of rapamycin and Myxoma virus can be used to treat diseases characterized by the presence of such cells, including cancer. The invention also relates to therapeutic use of Myxoma virus that does not express functional M135R.
1. A method for inhibiting a human cancer cell, comprising contacting a human cancer cell that is deficient in an innate antiviral response and permissive to Myxoma virus replication with an effective amount of a Myxoma virus that does not express functional M135R, wherein (i) part or all of the open reading frame that encodes M135R of the Myxoma virus is deleted, or (ii) part or all of the M135R gene regulatory region of the Myxoma virus is deleted wherein Myxoma virus inhibits human cancer cell; and wherein the human cancer cell is a glioma cell.
2. The method of claim 1 , wherein the cancer cell exhibits abnormal interferon signaling.
3. The method of claim 1 , wherein the Myxoma virus is genetically modified to express a therapeutic gene.
4. The method of claim 1 , wherein the contacting step is performed by administering to a human cancer patient an effective amount of the Myxoma virus that does not express functional M135R; and wherein the human cancer patient has glioma.
5. The method of claim 4 , wherein the Myxoma virus is genetically modified to express a therapeutic gene.
6. The method of claim 4 , wherein the virus is administered to the site of the cancer in the cancer patient by injection.
7. The method of claim 4 , wherein the virus is administered to the cancer patient systemically.
8. The method of claim 4 , wherein the human cancer patient is further administered with rapamycin.
9. The method of claim 4 , wherein the human cancer patient is further administered with an anti-cancer agent.
10. The method of claim 9 , wherein the anti-cancer agent is a chemotherapy agent.
11. The method of claim 1 , wherein part or all of the open reading frame that encodes M135R of the Myxoma virus is deleted.
12. The method of claim 1 , wherein part or all of the M135R gene regulatory region of the Myxoma virus is deleted.