Interferon-beta gene therapy improves survival in an immunocompetent mouse model of carcinomatosis.
BACKGROUND
Interferon-beta (IFNbeta) has multiple antitumor effects; however, its use has been limited by its short half-life in vivo. This limitation may be overcome by IFNbeta gene therapy. We evaluated adenovirus-IFNbeta therapy in an immunocompetent mouse model of carcinomatosis.


METHODS
Mice that were treated intraperitoneally 5 days after tumor (mouse ovarian teratoma) inoculation with an adenoviral vector that contains the mouse IFNbeta gene (Ad-IFNbeta), control adenoviral vector or saline solution. Mice were monitored for multiple outcome measures and toxicity. To determine the mechanism of antitumor effect, flow cytometry of ascites fluid was performed to differentiate immune cell populations. Nitric oxide in ascites fluid was measured with an electrochemical microsensor.


RESULTS
Tumor burden was decreased and survival was prolonged (P<.001) in the Ad-IFNbeta group after a single treatment of 3.3 x 10(8) plaque-forming units, with acceptable toxicity. By flow cytometry, an increase in the proportion of natural killer cells (from less than 2% of the gated population to more than 8%; P=.024) and an increase in macrophages were seen in the treated animals. Although there was a trend toward increased levels of nitric oxide in Ad-IFNbeta treatment groups, it was not statistically significant.


CONCLUSIONS
IFNbeta gene therapy results in decreased tumor burden and improved survival in an aggressive, immunocompetent mouse model of carcinomatosis. This therapy warrants further evaluation as a treatment for disseminated peritoneal cancer.
Hendren
Samantha K
SK
Department of Surgery, University of Pennsylvania, 3400 Spruce Street, 4 Silverstein, Philadelphia, PA 19104, USA.
Prabakaran
Indira
I
Buerk
Donald G
DG
Karakousis
Giorgos
G
Feldman
Michael
M
Spitz
Francis
F
Menon
Chandrakala
C
Fraker
Douglas L
DL
D000256:Adenoviridae; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007121:Immunocompetence; D016899:Interferon-beta / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D013724:Teratoma / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D016899:Interferon-beta