Engineered measles virus as a novel oncolytic therapy against prostate cancer

Pavlos Msaouel, Ianko D. Iankov, Cory Allen, John C. Morris, Veronika Von Messling, Roberto Cattaneo, Michael Koutsilieris, Stephen J. Russell, Evanthia Galanis

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

BACKGROUND. No curative therapy is currently available for locally advanced or metastatic prostate cancer. Oncolytic viruses represent a novel class of therapeutic agents that demonstrates no cross-resistance with existing approaches and can therefore be combined with conventional treatment modalities. Measles virus strains deriving from the Edmonston (MV-Edm) vaccine strain have shown considerable oncolytic activity against a variety of solid tumers and hematologic malignancies. In this study, we investigated the antitumor potential of recombinant MV-Edm derivatives as novel oncolytic agents against prostate cancer. METHODS. The susceptibility of prostate cancer cell lines (PC-3, DU-145, and LNCaP) to measles virus infection was demonstrated using an MV-Edm derivative expressing green fluorescent protein (GFP). MV-Edm replication in prostate cancer cell lines was assessed by one step viral growth curves. The oncolytic effect of an MV-Edm strain engineered to express the human carcinoembryonic antigen (CEA) was demonstrated in vitro by MTT assays and in vivo in subcutaneous PC-3 xenografts. CEA levels were quantitated in cell supernatants and mouse serum samples. RESULTS. Recombinant MV-Edm strains can effectively infect, replicate in and kill prostate cancer cells. Intratumoral administration of MV-CEA at a total dose of 6 x 106 TCID50 resulted in statistically significant tumor growth delay (P - 0.004) and prolongation of survival (P - 0.001) in a subcutaneous PC-3 xenograft model. Viral growth kinetics paralleled CEA production. CONCLUSIONS. MV-CEA has potent antitumor activity against prostate cancer cell lines and xenografts. Viral gene expression during treatment can be determined by monitoring of CEA levels in the serum; the latter could allow dose optimization and tailoring of individualized treatment protocols.

Original languageEnglish (US)
Pages (from-to)82-91
Number of pages10
JournalProstate
Volume69
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • CEA
  • MV-CEA
  • Measles virus
  • Prostate cancer
  • Virotherapy

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Msaouel, P., Iankov, I. D., Allen, C., Morris, J. C., Von Messling, V., Cattaneo, R., Koutsilieris, M., Russell, S. J., & Galanis, E. (2009). Engineered measles virus as a novel oncolytic therapy against prostate cancer. Prostate, 69(1), 82-91. https://doi.org/10.1002/pros.20857