Oncolytic adenovirus encoding a B7 protein or active fragment
The present disclosure provides a replication competent oncolytic adenovirus with selectivity for cancer cells, wherein the adenovirus comprises a transgene under the control of a promoter endogenous to the virus, wherein the transgene comprises a DNA sequence encoding a B7 protein or an active fragment thereof, compositions comprising same, methods of generating the viruses, and use of the viruses and compositions in treatment, particularly in the treatment of cancer.
1. A replication competent oncolytic adenovirus comprising SEQ ID NO: 96.
2. A pharmaceutical formulation of an adenovirus according to claim 1 , and a diluent or carrier.
3. A pharmaceutical formulation according to claim 2 , wherein the formulation is for parenteral administration.
4. A pharmaceutical formulation according to claim 3 , wherein the formulation comprises 2×10 12 viral particle/mL.
5. A pharmaceutical formulation according to claim 4 , wherein the viral particles are formulated in 5 mM HEPES, 20% glycerol with a final pH of 7.8.
6. A method of treatment comprising administering a therapeutically effective amount of a replication competent oncolytic adenovirus comprising SEQ ID NO: 96.
7. A method of treatment according to claim 6 , for the treatment of cancer.
8. A method of treatment according to claim 7 , wherein the cancer is selected from the group comprising: colorectal cancer, hepatoma, prostate cancer, pancreatic cancer, breast cancer, ovarian cancer, thyroid cancer, renal cancer, bladder cancer, head and neck cancer and lung cancer.
9. A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising a replication competent oncolytic adenovirus comprising SEQ ID NO: 96 and a diluent or carrier.
10. A method of treatment according to claim 9 , wherein the pharmaceutical formulation is administered parenterally.
11. A method according to claim 10 , wherein the dose per administration is in the range of 1×10 10 to 1×10 14 virus particles.
12. A method of treatment according to claim 11 , for the treatment of cancer.
13. A method of treatment according to claim 12 wherein the cancer is selected from the group comprising: colorectal cancer, hepatoma, prostate cancer, pancreatic cancer, breast cancer, ovarian cancer, thyroid cancer, renal cancer, bladder cancer, head and neck cancer and lung cancer.
14. The replication competent oncolytic adenovirus of claim 1 , wherein the virus comprises SEQ ID NO: 101.
15. A pharmaceutical formulation of an adenovirus according to claim 14 , and a diluent or carrier.
16. A pharmaceutical formulation according to claim 15 , wherein the formulation is for parenteral administration.
17. A pharmaceutical formulation according to claim 16 , wherein the formulation comprises 2×10 12 viral particle/mL.
18. A pharmaceutical formulation according to claim 17 , wherein the viral particles are formulated in 5 mM HEPES, 20% glycerol with a final pH of 7.8.