Adenovirus-mediated combination suicide and cytokine gene therapy for bladder cancer.
BACKGROUND
The present study tests the hypothesis that adenovirus-mediated transfer of murine IL-2 (ADV/RSV-mIL-2) alone or in combination with HSV-tk + GCV will improve antitumorigenic response in the murine MBT-2 model.


METHODS
mIL-2 production and toxicity were determined in vitro using an ELISA and a cell proliferation assay. Tumor-bearing animals were randomly assigned into four treatment groups and directly injected with combinations of ADV/RSV-tk and ADV/RSV-mIL-2. In a separate experiment, the above-mentioned groups were followed by two subsequent treatments with ADV/RSV-mIL-2.


RESULTS
Transduced MBT-2 cells were able to express mIL-2 in a time and dose dependent fashion. We could not demonstrate any improvement in antitumorigenic response with mIL-2 gene therapy alone or in combination with HSV-tk-suicide gene therapy over HSV-tk suicide gene therapy alone.


CONCLUSIONS
Although ADV/RSV-mIL-2 transduced MBT-2 cells were able to produce large amounts of mIL-2 in vitro, we could not demonstrate significant tumor growth inhibition by adding mIL-2 gene therapy to suicide gene therapy. The growth inhibitory effects of sequential suicide and cytokine gene therapy were transient and not superior to single dose suicide and cytokine gene therapy.
Freund
C T
CT
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Sutton
M A
MA
Dang
T
T
Contant
C F
CF
Rowley
D
D
Lerner
S P
SP
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006561:Herpes Simplex / Q000201:enzymology; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
D007376:Interleukin-2; D013937:Thymidine Kinase; D015774:Ganciclovir