Armed and targeted measles virus for chemovirotherapy of pancreatic cancer

• Verfasst von: Bossow, Sascha [VerfasserIn]
• Verfasst von: Grossardt, C. [VerfasserIn]
• Verfasst von: Temme, A. [VerfasserIn]
• Verfasst von: Leber, Mathias Felix [VerfasserIn]
• Verfasst von: Sawall, Stefan [VerfasserIn]
• Verfasst von: Rieber, E. P. [VerfasserIn]
• Verfasst von: Cattaneo, R. [VerfasserIn]
• Verfasst von: Kalle, Christof von [VerfasserIn]
• Verfasst von: Ungerechts, Guy [VerfasserIn]
• Titel: Armed and targeted measles virus for chemovirotherapy of pancreatic cancer
• Verf.angabe: S. Bossow, C. Grossardt, A. Temme, M.F. Leber, S. Sawall, E.P. Rieber, R. Cattaneo, C. von Kalle and G. Ungerechts
• E-Jahr: 2011
• Jahr: 24 June 2011
• Umfang: 11 S.
• Fussnoten: Gesehen am 02.06.2022
• Titel Quelle: Enthalten in: Cancer gene therapy
• Ort Quelle: New York, NY : Nature Publ. Group, 1999
• Jahr Quelle: 2011
• Band/Heft Quelle: 18(2011), 8, Seite 598-608
• ISSN Quelle: 1476-5500
• DOI: doi:10.1038/cgt.2011.30
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Chemotherapy
• Sach-SW: Gene therapy
• Sach-SW: Measles virus
• Sach-SW: Pancreatic cancer
• K10plus-PPN: 1805747932

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.