Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter

Kosei Hasegawa, Linh Pham, Michael K. O'Connor, Mark J Federspiel, Stephen J Russell, Kah-Whye Peng

Research output: Contribution to journalArticle

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Abstract

Purpose: MV-CEA is an oncolytic measles virus currently being tested in patients with ovarian cancer and whose propagation can be monitored by measuring blood carcinoembryonic antigen (CEA) levels. MV-NIS is an oncolytic measles virus coding for the thyroidal sodium iodide symporter (NIS) whose propagation can be mapped by serial radioiodine imaging. Expression of both CEA and MS genes from a single virus would combine sensitive, quantitative expression monitoring (CEA) with radioisotopic expression mapping (NIS). Because of the unfavorable replication kinetics of measles viruses expressing both CEA and NIS, we explored the feasibility of combining MV-CEA with MV-NIS for comprehensive virotherapy monitoring in ovarian cancer. Experimental Design and Results: Mice implanted with i.p. SKOV3ip.1 ovarian cancer xenografts received MV-CEA alone, MV-NIS alone, or a combination of MV-CEA plus MV-NIS. Viral gene expression was monitored by measuring blood CEA levels, and the location of virus-infected cells was monitored by gamma camera imaging. Surprisingly, mice receiving the combination of MV-CEA plus MV-NIS showed greatly superior responses to therapy, but this was associated with 10-fold lower plasma levels of CEA compared with mice treated with MV-CEA alone. In vitro studies showed superior replication kinetics of MV-NIS relative to MV-CEA. The gamma camera scans were considerably less sensitive than the plasma CEA marker for monitoring virus infection. Conclusions: Dual therapy with MV-CEA and MV-NIS is superior to treatment with either virus alone, and it allows noninvasive monitoring of virotherapy via soluble marker peptide and gamma camera imaging. This has important implications for the clinical development of oncolytic measles viruses.

Original languageEnglish (US)
Pages (from-to)1868-1875
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number6
DOIs
StatePublished - Mar 15 2006

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Measles virus
Carcinoembryonic Antigen
Ovarian Neoplasms
Oncolytic Viruses
Therapeutics
sodium-iodide symporter
Viruses
Radionuclide Imaging
Gamma Cameras
Viral Genes
Virus Diseases
Heterografts

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter. / Hasegawa, Kosei; Pham, Linh; O'Connor, Michael K.; Federspiel, Mark J; Russell, Stephen J; Peng, Kah-Whye.

In: Clinical Cancer Research, Vol. 12, No. 6, 15.03.2006, p. 1868-1875.

Research output: Contribution to journalArticle

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