Armed and targeted measles virus for chemovirotherapy of pancreatic cancer

S. Bossow, C. Grossardt, A. Temme, M. F. Leber, S. Sawall, E. P. Rieber, R. Cattaneo, C. Von Kalle, G. Ungerechts

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

No curative therapy is currently available for locally advanced or metastatic pancreatic cancer. Therefore, new therapeutic approaches must be considered. Measles virus (MV) vaccine strains have shown promising oncolytic activity against a variety of tumor entities. For specific therapy of pancreatic cancer, we generated a fully retargeted MV that enters cells exclusively through the prostate stem cell antigen (PSCA). Besides a high-membrane frequency on prostate cancer cells, this antigen is expressed on pancreatic adenocarcinoma, but not on non-neoplastic tissue. PSCA expression levels differ within heterogeneous tumor bulks and between human pancreatic cell lines, and we could show specific infection of pancreatic adenocarcinoma cell lines with both high-and low-level PSCA expression. Furthermore, we generated a fully retargeted and armed MV-PNP-anti-PSCA to express the prodrug convertase purine nucleoside phosphorylase (PNP). PNP, which activates the prodrug fludarabine effectively, enhanced the oncolytic efficacy of the virus on infected and bystander cells. Beneficial therapeutic effects were shown in a pancreatic cancer xenograft model. Moreover, in the treatment of gemcitabine-resistant pancreatic adenocarcinoma cells, no cross-resistance to both MV oncolysis and activated prodrug was detected.

Original languageEnglish (US)
Pages (from-to)598-608
Number of pages11
JournalCancer Gene Therapy
Volume18
Issue number8
DOIs
StatePublished - Aug 1 2011

Keywords

  • measles virus
  • oncolysis
  • pancreatic cancer
  • prodrug-converting enzyme
  • single-chain antibody

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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  • Cite this

    Bossow, S., Grossardt, C., Temme, A., Leber, M. F., Sawall, S., Rieber, E. P., Cattaneo, R., Von Kalle, C., & Ungerechts, G. (2011). Armed and targeted measles virus for chemovirotherapy of pancreatic cancer. Cancer Gene Therapy, 18(8), 598-608. https://doi.org/10.1038/cgt.2011.30