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.
Cheng
W-S
WS
Clinical Immunology, Rudbeck Laboratory, Uppsala University, Sweden.
Dzojic
H
H
Nilsson
B
B
Tötterman
T H
TH
Essand
M
M
D000256:Adenoviridae / Q000378:metabolism*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014779:Virus Replication
D017500:Adenovirus E1A Proteins; D013739:Testosterone