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

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

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)732-738
Number of pages7
JournalCancer Gene Therapy
Volume13
Issue number8
DOIs
StatePublished - Aug 2006

Keywords

  • Measles virus
  • Ovarian cancer
  • Pharmacokinetics
  • Soluble CEA

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Pharmacokinetics of oncolytic measles virotherapy: Eventual equilibrium between virus and tumor in an ovarian cancer xenograft model'. Together they form a unique fingerprint.

Cite this