An immunocompetent murine model for oncolysis with an armed and targeted measles virus

Guy Ungerechts, Christoph Springfeld, Marie E. Frenzke, Johanna Lampe, William B. Parker, Eric J. Sorscher, Roberto Cattaneo

Research output: Contribution to journalArticle

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Abstract

An immunocompetent model is required to test therapeutic regimens for clinical trials with the oncolytic measles virus (MV). Toward developing this model, a retargeted MV that enters murine colon adenocarcinoma cells forming tumors in syngeneic C57BL/6 mice was generated. Since MV infection tends to be less efficient in murine than in human cells, the targeted virus was also armed with the prodrug convertase, purine nucleoside phosphorylase (PNP), and named MV-PNP-antiCEA. We have shown before that in cultured cells, infection with this virus activated the prodrug, 6-methylpurine-2′-deoxyriboside (MeP-dR), causing extensive cytotoxicity. When injected intratumorally (IT), MV-PNP-antiCEA inhibited subcutaneous tumor growth marginally, but subsequent administration of the prodrug enhanced the oncolytic effect. Systemic delivery of MV-PNP-antiCEA alone had no substantial oncolytic effects, but in combination with the prodrug it was therapeutic, revealing synergistic effects between virus and prodrug. Immunosuppression with cyclophosphamide (CPA) retarded the appearance of MV neutralizing antibodies and enhanced oncolytic efficacy: survival was 100%, with 9 out of 10 animals going into complete remission. This immunocompetent murine model facilitates the testing of therapeutic regimens for clinical trials.

Original languageEnglish (US)
Pages (from-to)1991-1997
Number of pages7
JournalMolecular Therapy
Volume15
Issue number11
DOIs
StatePublished - Nov 2007

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Measles virus
Purine-Nucleoside Phosphorylase
Prodrugs
Virus Diseases
Clinical Trials
Oncolytic Viruses
Viruses
Neutralizing Antibodies
Inbred C57BL Mouse
Cyclophosphamide
Immunosuppression
Cultured Cells
Neoplasms
Colon
Adenocarcinoma
Therapeutics
Survival
Growth

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Ungerechts, G., Springfeld, C., Frenzke, M. E., Lampe, J., Parker, W. B., Sorscher, E. J., & Cattaneo, R. (2007). An immunocompetent murine model for oncolysis with an armed and targeted measles virus. Molecular Therapy, 15(11), 1991-1997. https://doi.org/10.1038/sj.mt.6300291

An immunocompetent murine model for oncolysis with an armed and targeted measles virus. / Ungerechts, Guy; Springfeld, Christoph; Frenzke, Marie E.; Lampe, Johanna; Parker, William B.; Sorscher, Eric J.; Cattaneo, Roberto.

In: Molecular Therapy, Vol. 15, No. 11, 11.2007, p. 1991-1997.

Research output: Contribution to journalArticle

Ungerechts, G, Springfeld, C, Frenzke, ME, Lampe, J, Parker, WB, Sorscher, EJ & Cattaneo, R 2007, 'An immunocompetent murine model for oncolysis with an armed and targeted measles virus', Molecular Therapy, vol. 15, no. 11, pp. 1991-1997. https://doi.org/10.1038/sj.mt.6300291
Ungerechts G, Springfeld C, Frenzke ME, Lampe J, Parker WB, Sorscher EJ et al. An immunocompetent murine model for oncolysis with an armed and targeted measles virus. Molecular Therapy. 2007 Nov;15(11):1991-1997. https://doi.org/10.1038/sj.mt.6300291
Ungerechts, Guy ; Springfeld, Christoph ; Frenzke, Marie E. ; Lampe, Johanna ; Parker, William B. ; Sorscher, Eric J. ; Cattaneo, Roberto. / An immunocompetent murine model for oncolysis with an armed and targeted measles virus. In: Molecular Therapy. 2007 ; Vol. 15, No. 11. pp. 1991-1997.
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