Claims
- 1. A replication-competent adenovirus vector comprising an adenovirus gene essential for replication, under transcriptional control of a first melanoma cell specific transcriptional regulatory element (TRE).
- 2. The adenovirus vector according to claim 1, wherein said first melanoma cell specific TRE comprises a promoter derived from the 5′ region of a gene selected from the group consisting of tyrosinase, tyrosinase-related protein 2 (TRP2), MIA, microphthalmia associated transcription factor (MITF); melanocyte-specific gene 1; melanocyte-specific tyrosinase-related protein-1, and MART-1.
- 3. The adenovirus vector according to claim 1, wherein said first melanoma cell specific TRE comprises an enhancer derived from the 5′ region of a gene selected from the group consisting of tyrosinase, tyrosinase-related protein 2 (TRP2), MIA, microphthalmia associated transcription factor (MITF); melanocyte-specific gene 1; melanocyte-specific tyrosinase-related protein-1, and MART-1.
- 4. The adenovirus vector of claim 1, wherein said first melanoma cell-specific TRE comprises a human promoter or enhancer.
- 5. The adenovirus vector of claim 1, wherein said adenovirus gene essential for replication is under the transcriptional control of a composite regulatory element comprising a heterologous promoter and enhancer.
- 6. The adenovirus vector of claim 1, further comprising an adenovirus gene essential for replication under transcriptional control of a second melanoma cell specific transcriptional regulatory element (TRE).
- 7. The adenovirus vector of claim 6, wherein said second melanoma specific TRE is different from said first melanoma specific TRE.
- 8. The adenovirus vector of claim 6, wherein said second melanoma cell specific TRE comprises a promoter derived from the 5′ region of a gene selected from the group consisting of tyrosinase, tyrosinase-related protein 2 (TRP2), MIA, microphthalmia associated transcription factor (MITF); melanocyte-specific gene 1; melanocyte-specific tyrosinase-related protein-1, and MART-1.
- 9. The adenovirus vector of claim 6, wherein said second melanoma cell specific TRE comprises an enhancer derived from the 5′ region of a gene selected from the group consisting of tyrosinase, tyrosinase-related protein 2 (TRP2), MIA, microphthalmia associated transcription factor (MITF); melanocyte-specific gene 1; melanocyte-specific tyrosinase-related protein-1, and MART-1.
- 10. The adenovirus vector of claim 1, wherein said first melanoma cell specific TRE comprises two or more enhancers.
- 11. The adenovirus vector of claim 6 wherein said second melanoma specific TREs comprises two or more enhancers.
- 12. 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.
- 13. The adenovirus vector of claim 1, wherein said adenoviral gene essential for replication is an early gene.
- 14. The adenovirus vector of claim 1 wherein said adenoviral gene essential for replication is a late gene.
- 15. The adenovirus vector of claim 13, wherein said adenoviral gene essential for replication is E1A or E1B.
- 16. The adenovirus vector of claim 13, wherein E1A or E1B has a mutation in or deletion of its endogenous promoter.
- 17. The adenovirus vector of claim 16, wherein E1B has a deletion of the 19-kDa region.
- 18. A composition comprising:
A replication-competent adenovirus vector comprising an adenovirus gene essential for replication, under transcriptional control of a melanoma cell specific transcriptional regulatory element (TRE); and a pharmaceutically acceptable excipient.
- 19. An isolated host cell comprising the adenovirus vector of claim 1.
- 20. A method for suppressing melanoma tumor growth in an individual, the method comprising:
administering a melanoma cell-specific adenovirus vector, said vector comprising an adenoviral gene essential for replication under transcriptional control of a melanoma cell-specific-transcriptional regulatory element (TRE) comprising a promoter or enhancer derived from the 5′ region of a gene selected from the group consisting of tyrosinase, tyrosinase-related protein 2 (TRP2), MIA, microphthalmia associated transcription factor (MITF); melanocyte-specific gene 1; melanocyte-specific tyrosinase-related protein-1, and MART-1.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application in a continuation-in-part of U.S. patent application Ser. No. 09/814,357, filed Mar. 21, 2001 which claims the benefit of U.S. Provisional Patent Application No. 60/192,015 filed Mar. 24, 2000; and a continuation-in-part of U.S. patent application Ser. No. 09/814,351, filed Mar. 21, 2001 which claims the benefit of U.S. Provisional Patent Application No. 60/192,156 filed Mar. 24, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60192015 |
Mar 2000 |
US |
|
60192156 |
Mar 2000 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
09814357 |
Mar 2001 |
US |
Child |
10053886 |
Jan 2002 |
US |
Parent |
09814351 |
Mar 2001 |
US |
Child |
10053886 |
Jan 2002 |
US |