1. ¹Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA
2. ²Toxicology Core, Mayo Clinic College of Medicine, Rochester, MN, USA
3. ³Viral Vector Production Facility, Mayo Clinic College of Medicine, Rochester, MN, USA

Correspondence: Dr SJ Russell, Guggenheim 18, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. E-mail: sjr@mayo.edu

Received 9 October 2005; Revised 19 December 2005; Accepted 8 January 2006; Published online 10 March 2006.

Abstract

Because of their ability to replicate, the dose–response relationships of oncolytic viruses cannot easily be predicted. To better understand the pharmacokinetics of virotherapy in relation to viral dose and schedule, we administered MV-CEA intraperitoneally in an orthotopic mouse model of ovarian cancer. MV-CEA is an attenuated oncolytic measles virus engineered to express soluble human carcinoembryonic antigen (CEA), and the virus is currently undergoing phase I clinical testing in patients with ovarian cancer. Plasma CEA levels correlate with numbers of virus-infected tumor cells at a given time, and were used as a surrogate to monitor the profiles of viral gene expression over time. The antineoplastic activity of single- or multiple-dose MV-CEA was apparent over a wide range of virus doses (10³–10⁸ TCID₅₀), with little reduction in observed antitumor efficacy, even at the lowest tested dose. However, analysis of CEA profiles of treated mice was highly informative, illustrating the variability in virus kinetics at different dose levels. The highest doses of virus were associated with higher initial levels of tumor cell killing, but the final outcome of MV-CEA therapy at all dose levels was a partial equilibrium between virus and tumor, resulting in significant slowing of tumor growth and enhanced survival of the mice.