Adenovirus-mediated suicide gene therapy for bladder cancer: comparison of the cytomegalovirus- and Rous sarcoma virus-promoter.
BACKGROUND
To compare efficacy and toxicity of the human cytomegalovirus-immediate-early (CMV) promoter and the Rous-sarcoma-virus (RSV) promoter to express thymidine kinase (tk) for adenovirus-mediated suicide gene therapy of experimental bladder cancer in vivo and in vitro.


METHODS
In vitro: 3 human (5637, RT-4 and TCC-SUP) and one murine (MBT-2) bladder cancer cell line were exposed to ADV/RSV-tk or ADV/CMV-tk vectors and cell survival was determined. In vivo: Subcutaneous tumors were established and adenovirus vectors were injected 10 days later.


RESULTS
In vitro: ADV/CMV-tk was up to 4 times more potent in terms of cell killing than ADV/RSV-tk. In vivo: ADV/CMV-tk had a three-fold higher antitumor potency per viral particle as compared to ADV/RSV-tk. Higher doses of ADV/CMV-tk caused treatment-associated hepatotoxicity.


CONCLUSIONS
Our results confirm the efficacy of adenovirus-mediated tk suicide gene therapy in the treatment of experimental bladder cancer. Dose-related toxicity was greater with the use of ADV/CMV-tk, but lower doses achieved the same efficacy as ADV/RSV-tk.
Freund
C T
CT
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Tong
X W
XW
Block
A
A
Contant
C F
CF
Kieback
D G
DG
Rowley
D R
DR
Lerner
S P
SP
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D003587:Cytomegalovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
D000956:Antigens, Viral; D017874:Immediate-Early Proteins; C044582:immediate-early proteins, cytomegalovirus; D013937:Thymidine Kinase