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Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

Cancer Gene Therapy volume 13, pages 732–738 (2006)Cite this article

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.

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Acknowledgements

We thank Maureen Craft for excellent secretarial support and the Molecular Medicine Program Viral Vector Production Laboratory (Guy Griesmann, Kirsten Langfield, Julie Sauer, Sharon Stephan, Henry Walker and Troy Wegman) for supply of the MV-CEA virus. This work was supported by the Olivier S and Jennie O Donaldson Charitable Trust, George M Eisenberg Foundation for Charities and NIH Grants CA100634, CA15083 and HL66958.

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Authors and Affiliations

  1. Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA

    K-W Peng, E M Hadac, B D Anderson, R Myers, M Harvey, S M Greiner, D Soeffker, M J Federspiel & S J Russell

  2. Toxicology Core, Mayo Clinic College of Medicine, Rochester, MN, USA

    K-W Peng, R Myers, M Harvey, S M Greiner, D Soeffker & S J Russell

  3. Viral Vector Production Facility, Mayo Clinic College of Medicine, Rochester, MN, USA

    M J Federspiel

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  1. K-W Peng
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  2. E M Hadac
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Correspondence to S J Russell.

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Peng, KW., Hadac, E., Anderson, B. et al. Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model. Cancer Gene Ther 13, 732–738 (2006). https://doi.org/10.1038/sj.cgt.7700948

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