Use of adenovirus and nucleic acids coding therefor
This invention relates to the use of an adenovirus to treat cancer, for example. The adenovirus may be replication deficient in cells that lack Y box binding protein. The adenovirus may encode an oncogene or an oncogene product, which may transactivate at least one viral gene.
1. A method for the treatment of cancer in a patient, wherein the method comprises testing for the presence of YB-1 in the nucleus of cancer cells of a sample from the patient, and administering an adenovirus to the patient if cancer cells have YB-1 in the nucleus, wherein the adenovirus expresses E1B55 kDa and is replication deficient in cells that lack Y box binding protein 1 (YB-1) in the nucleus and replication competent in cells that have YB-1 in the nucleus; wherein the virus encodes an oncogene protein that transactivates E1B55 kDa, and wherein the adenovirus is dl520 lacking a functional CR3 domain.
2. The method of claim 1 , wherein dl520 is E1B 19 K-minus.
3. The method of claim 1 , wherein the adenovirus is capable of replicating in cells that are p53-positive or p53-negative.
4. The method of claim 1 , wherein the oncogene protein is E1A.
5. The method of claim 4 , wherein the E1A does not induce nuclear localization of YB-1.
6. The method of claim 1 , wherein the oncogene protein is E1A12S.
7. The method of claim 1 , wherein the oncogene protein is encoded by a gene that is under the control of a tissue and/or tumor specific promoter.
8. The method of claim 1 , wherein the virus encodes YB-1.
9. The method of claim 8 , wherein the YB-1 is under the control of a tissue and/or tumor specific promoter.
10. The method of claim 1 , wherein the cancer is formed from a tumor, or part thereof, which is resistant to pharmacological agents.
11. The method of claim 10 , wherein the cells that form the tumor, or part thereof, overexpress membrane-bound transport protein P glycoprotein.
12. The method of claim 10 , wherein the pharmacological agent is an anti-tumor agent.
13. The method of claim 12 , wherein the anti-tumor agent is a cytostatic agent.
14. The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, ovary carcinoma, prostate carcinoma, osteosarcoma, glioblastoma, melanoma, small cell lung carcinoma, and colorectal carcinoma.
15. The method of claim 1 , wherein the presence of YB-1 is tested by means of a YB-1 binding agent, wherein the agent is selected from the group consisting of an antibody, an anticaline, an aptamer, an aptazyme and a spiegelmer.