Recombinant oncolytic adenovirus for human melanoma
View Patent ↗The invention provides melanoma cell specific adenovirus vectors, which preferentially replicate in melanoma cells.
1. A replication-competent adenovirus vector for selective cytolysis of a melanoma target cell comprising an adenovirus gene essential for replication, under transcriptional control of a first melanoma cell specific transcriptional regulatory element (TRE) derived from the 5′ region of a gene, said TRE being selected from the group consisting of a tyrosinase TRE sequence presented as SEQ ID NO: 4, SEQ ID NO: 7, and SEQ ID NO: 16.
2. The adenovirus vector according to claim 1 , wherein said first melanoma cell specific TRE comprises the tyrosinase TRE sequence presented as SEQ ID NO: 4.
3. The adenovirus vector according to claim 1 , wherein said first melanoma cell specific TRE comprises the tyrosinase TRE sequence presented as SEQ ID NO: 7.
4. The adenovirus vector according to claim 1 , wherein said first melanoma cell-specific TRE comprises the tyrosinase TRE sequence presented as SEQ ID NO: 16.
5. The adenovirus vector of claim 1 , wherein said first melanoma cell specific TRE comprises two or more enhancers.
6. The adenovirus vector of claim 1 , wherein the adenoviral vector comprises co-transcribed first and second adenoviral genes under transcriptional control of said first melanoma cell-specific TRE wherein the second gene is under translational control of an IRES.
7. The adenovirus vector of claim 1 , wherein said adenoviral gene essential for replication is an early gene.
8. The adenovirus vector of claim 1 , wherein said adenoviral gene essential for replication is a late gene.
9. The adenovirus vector of claim 7 , wherein said adenoviral gene essential for replication is E1A or E1B.
10. The adenovirus vector of claim 7 , wherein E1A or E1B has a mutation in or deletion of its endogenous promoter.
11. The adenovirus vector of claim 10 , wherein E1B has a deletion of the 19-kDa region.
12. A composition comprising:
the replication-competent adenovirus vector according to claim 1 ; and a pharmaceutically acceptable excipient.
13. An isolated host cell comprising the adenovirus vector of claim 1 .
14. A method for suppressing melanoma tumor growth in an individual, the method comprising:
administering to the individual the melanoma cell-specific adenovirus vector according to claim 1 .
15. A replication competent adenovirus vector according to claim 1 ; wherein the difference in yield of said adenovirus between a melanoma cell and non-melanoma cell is at least about 1000 fold following infection of said melanoma cell.
16. The replication competent adenovirus vector of claim 15 , wherein the adenoviral vector comprises co-transcribed first and second adenoviral genes under transcriptional control of said melanoma cell-specific TRE wherein the second gene is under transcriptional control of an IRES.
17. The replication competent adenovirus vector of claim 15 , wherein said melanoma cell specific transcriptional regulatory element (TRE) comprises SEQ ID NO: 16.
18. The replication competent adenovirus vector of claim 15 , wherein said melanoma cell specific transcriptional regulatory element (TRE) comprises SEQ ID NO: 7.
19. The replication competent adenovirus vector of claim 15 , wherein said melanoma cell specific transcriptional regulatory element (TRE) comprises SEQ ID NO: 4.