An oncolytic conditionally replicating adenovirus for hormone-dependent and hormone-independent prostate cancer

• 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.

Nyckelord

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

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)