Journal
GENE THERAPY
Volume 11, Issue 6, Pages 552-559Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3302181
Keywords
adenovirus; ovarian neoplasms; virus replication, biological therapy
Categories
Funding
- NCI NIH HHS [R01 CA93796, R01 CA94084, R01 CA83821, P50 CA83591] Funding Source: Medline
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Conditionally replicating adenoviruses (CRADs) take advantage of tumor-specific characteristics for preferential replication and subsequent oncolysis of cancer cells. The antitumor effect is determined by the capability to infect tumor cells. Here, we used RGDCRADcox-2R, which features the cyclooxygenase-2 promoter for replication control and an integrin binding RGD-4C motif for enhanced infectivity of ovarian cancer cells. RGDCRADcox-2R replicated in and killed human ovarian cancer cells effectively, while the replication in nonmalignant cells was low. Importantly, the therapeutic efficacy, as evaluated in an orthotopic model of peritoneally disseminated ovarian cancer, was significantly improved and toxicity was lower than with a wild-type virus. Thus, this CRAD could be tested for treatment of ovarian cancer in humans.
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