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Engineered measles virus as a novel oncolytic therapy against prostate cancer

  1. Pavlos Msaouel1,2,
  2. Ianko D. Iankov1,
  3. Cory Allen1,
  4. John C. Morris3,
  5. Veronika von Messling4,
  6. Roberto Cattaneo1,
  7. Michael Koutsilieris2,
  8. Stephen J. Russell1,
  9. Evanthia Galanis MD1,5,*

Article first published online: 30 OCT 2008

DOI: 10.1002/pros.20857

Issue

The Prostate

The Prostate

Volume 69, Issue 1, pages 82–91, 1 January 2009

Additional Information

How to Cite

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

Author Information

  1. 1

    Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota

  2. 2

    Department of Experimental Physiology, National and Kapodistrian University of Athens, Athens, Greece

  3. 3

    Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, Rochester, Minnesota

  4. 4

    INRS-Institut Armand-Frappier, Université du Québec, Laval, Quebec, Canada

  5. 5

    Department of Oncology, Mayo Clinic, Rochester, Minnesota

*200 First Street SW, Rochester, MN 55905.

Publication History

  1. Issue published online: 21 NOV 2008
  2. Article first published online: 30 OCT 2008
  3. Manuscript Accepted: 21 AUG 2008
  4. Manuscript Received: 16 JUN 2008

Funded by

  • Mayo Clinic Prostate SPORE. Grant Number: P50 CA 091956

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Keywords:

  • CEA;
  • measles virus;
  • MV-CEA;
  • prostate cancer;
  • virotherapy

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 × 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. Prostate 69: 82–91, 2009. © 2008 Wiley–Liss, Inc.

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