Claims
- 1. A replication-competent adenovirus vector for selective cytolysis of a target cell, comprising:a first adenovirus gene essential for replication under transcriptional control of a first heterologous transcriptional regulatory element (TRE) and at least a second adenovirus gene under transcriptional control of a second heterologous TRE, wherein the first and the second heterologous TREs are cell-specific, the first heterologous is different from the second heterologous TRE, and the heterologous TREs are functional in the same cell.
- 2. The adenovirus vector of claim 1, wherein said adenovirus gene essential for replication is an adenovirus early gene.
- 3. The adenovirus vector of claim 2, wherein said gene essential for replication is the adenovirus E1A gene.
- 4. The adenovirus vector of claim 1, wherein said gene essential for replication is an adenovirus late gene.
- 5. The adenovirus vector of claim 1, wherein said second adenovirus gene is essential for replication.
- 6. The adenovirus vector of claim 5, wherein said first and second genes are adenovirus early genes.
- 7. The adenovirus vector of claim 1, wherein said vector comprises a cytotoxic gene.
- 8. The adenovirus vector of claim 1, wherein the first heterologous TRE is prostate cell-specific.
- 9. The adenovirus vector of claim 1, wherein the first heterologous TRE is a PSA-TRE.
- 10. An isolated host cell comprising the adenovirus vector of claim 1.
- 11. A composition comprising the adenovirus vector of claim 1 and a pharmaceutically acceptable excipient.
- 12. The adenovirus vector of claim 1, wherein said first heterologous TRE is selected from the group consisting of a prostate-specific antigen (PSA) transcriptional regulatory element (PSA-TRE), a probasin transcriptional regulatory element (PB-TRE), a human glandular kallikrein transcriptional regulatory element (HKLK2-TRE), a carcinoembryonic antigen transcriptional regulatory element (CEA-TRE), an α-fetoprotein transcriptional regulatory element (AFP-TRE), a urokinase-type plasminogen activator transcriptional regulatory element (uPA TRE); a mucin transcriptional regulatory element (MUC1-TRE) and a HER-2/neu transcriptional regulatory element (HER-2/neu TRE).
- 13. The adenovirus vector of claim 12, wherein said adenovirus gene essential for replication is an adenovirus early gene.
- 14. The adenovirus vector of claim 12, wherein said vector comprises a therapeutic gene.
- 15. The adenovirus vector of claim 12, wherein said vector comprises a cytotoxic gene.
- 16. An isolated host cell comprising the adenovirus vector of claim 12.
- 17. A composition comprising the adenovirus vector of claim 12, and a pharmaceutically acceptable excipient.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Ser. No. 60/039,597 filed Mar. 3, 1997; U.S. Serial No. 60/039,762, filed Mar. 3, 1997; U.S. Ser. No. 60/039,763, filed Mar. 3, 1997; and U.S. Ser. No. 60/054,523, filed Aug. 4, 1997.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
5698443 |
Henderson et al. |
Dec 1997 |
A |
5998205 |
Hallenbeck et al. |
Dec 1999 |
A |
6197293 |
Henderson et al. |
Mar 2001 |
B1 |
Foreign Referenced Citations (2)
Number |
Date |
Country |
96-17053 |
Jun 1996 |
WO |
96-34969 |
Nov 1996 |
WO |
Provisional Applications (4)
|
Number |
Date |
Country |
|
60/039597 |
Mar 1997 |
US |
|
60/039762 |
Mar 1997 |
US |
|
60/039763 |
Mar 1997 |
US |
|
60/054523 |
Aug 1997 |
US |