An oncolytic conditionally replicating adenovirus for hormone-dependent and hormone-independent prostate cancer
2006 (English)In: Cancer Gene Therapy, ISSN 0929-1903, Vol. 13, no 1, 13-20 p.Article in journal (Refereed) Published
The use of conditionally replicating adenoviruses offers an attractive complementary treatment strategy for localized prostate cancer. We have produced a replicating adenovirus, Ad[I/PPT-E1A], where E1A gene expression is controlled by a recombinant regulatory sequence designated PPT. The PPT sequence comprises a PSA enhancer, a PSMA enhancer and a T-cell receptor gamma-chain alternate reading frame protein promoter, and it is shielded from transcriptional interference from adenoviral backbone sequences by an H19 insulator. Ad[I/PPT-E1A] yields prostate-specific E1A protein expression, viral replication and cytolysis in vitro. Furthermore, Ad[I/PPT-E1A] considerably regresses the growth of subcutaneous LNCaP prostate cancer tumors in nude mice. Importantly, the viral replication and cytolytic effect of Ad[I/PPT-E1A] are independent of the testosterone levels in the prostate cancer cells. This may be beneficial in a clinical setting since many prostate cancer patients are treated with androgen withdrawal. In conclusion, Ad[I/PPT-E1A] may prove to be useful in the treatment of localized prostate cancer.
Place, publisher, year, edition, pages
2006. Vol. 13, no 1, 13-20 p.
Adenoviridae/*metabolism, Adenovirus E1A Proteins/genetics/metabolism, Animals, Gene Expression Regulation; Neoplastic, Genetic Vectors/metabolism/therapeutic use, Humans, Male, Mice, Mice; Inbred C57BL, Mice; Nude, Neoplasms; Hormone-Dependent/genetics/*metabolism, Prostatic Neoplasms/*metabolism, Testosterone/metabolism, Time Factors, Transfection, Virus Replication
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-92862DOI: 10.1038/sj.cgt.7700881.PubMedID: 16052227OAI: oai:DiVA.org:uu-92862DiVA: diva2:166168