1. ¹Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
2. ²Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
3. ³Department of Oral Diagnostic Service, Howard University, Washington, DC, USA
4. ⁴Department of Obstetrics and Gynecology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
5. ⁵Department of Molecular Microbiology and Immunology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
6. ⁶Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

Correspondence: Chien-Fu Hung, Department of Pathology, The Johns Hopkins University School of Medicine, CRBII 307, 1550 Orleans Street, Baltimore, Maryland 21231, USA. E-mail: chung2@jhmi.edu

Received 7 August 2008; Accepted 26 April 2009; Published online 26 May 2009.

Abstract

Metastatic ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. The lack of effective treatment for patients with advanced ovarian cancer warrants development of innovative therapies. Cancer therapy using oncolytic viruses represents a promising new approach for controlling tumors. Vaccinia virus has been shown to preferentially infect tumor cells but not normal tissue. However, oncolytic therapy using recombinant viruses faces the limitation of viral clearance due to generation of neutralizing antibodies. In the current study, we found that cyclooxygenase-2 (Cox-2) inhibitors circumvented this limitation, enabling repeated administration of vaccinia virus without losing infectivity. We quantified the antivaccinia antibody response using enzyme-linked immunosorbent assay (ELISA) and neutralization assays to show that treatment of Cox-2 inhibitors inhibited the generation of neutralizing antibodies. Furthermore, we showed that combination treatment of Cox-2 inhibitors with vaccinia virus was more effective that either treatment alone in treating MOSEC/luc tumor-bearing mice. Thus, the combination of Cox-2 inhibitors and vaccinia virus represents a potential innovative approach to controlling ovarian tumors.