The adenoviral mutant dl922-947 has potent activity in a variety of
tumors. We investigated the efficacy of dl922-947 in ovarian
carcinoma; compared its activity to wild-type adenovirus, dl309, and
dl1520; and investigated the use of
icodextrin to enhance activity in vivo. We also assessed the utility of
luciferase bioluminescence imaging to quantify the response of human ovarian
carcinoma xenografts to dl922-947. Ovarian
carcinoma cell lines were transfected in vitro with dl922-947, adenovirus 5 wild-type (Ad5 WT), dl309, and
dl1520 and monitored for S-phase induction,
viral protein expression, replication, and overall survival. In vivo, the efficacy of dl922-947 when delivered in PBS or
icodextrin to female nude mice bearing IGROV1 xenografts was determined. In vitro, dl922-947 induced lysis with greater efficacy than Ad5 WT, dl309, or
dl1520 in all ovarian
carcinoma cell lines tested, which was associated with earlier expression of
viral proteins and S-phase induction. The lytic effect in immortalized ovarian surface epithelial cells confirmed that cellular
retinoblastoma pathway status is a strong determinant of dl922-947 activity. In vivo, i.p. delivery of dl922-947 (5 x 10(9) particles daily x 5) increased median survival from 20 to 96 days (P < 0.0001) and delivery in
icodextrin-enhanced survival further. However, delayed hepatic toxicity was evident in some dl922-947-treated mice, which was not dependent upon viral replication within
tumor cells or the liver. dl922-947 has potency in ovarian
carcinoma and i.p. delivery in
icodextrin may enhance this activity. Immunocompetent models of ovarian
carcinoma are required for further evaluation of hepatotoxicity.