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.
Bibliographical noteFunding Information:
We thank Drs Bin Liu and Minghui Wang (Division of Human Gene Therapy, University of Alabama at Birmingham) for statistical analysis and quantitative PCR assays. This work was supported by University of Helsinki Internal Funds, the Sigrid Juselius Foundation, Finnish Cancer Society, Biocentrum Helsinki, Emil Aaltonen Foundation, Maud Kuistila Foundation, Finnish Medical Foundation, Academy of Finland, Ida Montin Foundation, Biomedicum Helsinki-Foundation, the NIH (R01 CA94084, R01 CA83821, R01 CA93796, P50 CA83591), Susan B. Komen Foundation, Deutsche For-schungsgemeinschaft (BA2076/1-2), and University of Alabama Health Services Foundation. We thank Drs H Inoue and T Tanabe for providing a plasmid phPES3 containing the cox-2 promoter.
- Biological therapy
- Ovarian neoplasms
- Virus replication