Adenovirus-mediated gene therapy of ovarian cancer in a mouse model.
OBJECTIVE
Our purpose was to test the feasibility of adenovirus-mediated gene therapy of ovarian cancer.


METHODS
Ovarian cancer cell lines were exposed to an adenovirus vector expressing a reporter gene (lacZ) and to the same vector bearing the herpes simplex virus thymidine kinase gene (Ad.RSVtk) followed by ganciclovir. lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injected intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSVtk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests.


RESULTS
Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSVtk all cell lines showed significant (p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established subcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSVtk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Additionally, no intraperitoneal tumors were observed in treated mice.


CONCLUSIONS
Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSVtk. These data support the development of this method for human clinical trials.
Behbakht
K
K
Division of Gynecologic Oncology, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Benjamin
I
I
Chiu
H C
HC
Eck
S L
SL
Van Deerlin
P G
PG
Rubin
S C
SC
Boyd
J
J
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000628:therapy*; D014407:Tumor Cells, Cultured
D015774:Ganciclovir