Armed and targeted measles virus for chemovirotherapy of pancreatic cancer
Autor: | Christian Grossardt, A Temme, Guy Ungerechts, C von Kalle, E P Rieber, Sascha Bossow, Roberto Cattaneo, Stefanie Sawall, Mathias F. Leber |
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Rok vydání: | 2011 |
Předmět: |
Male
Cancer Research Antineoplastic Agents Mice SCID Adenocarcinoma GPI-Linked Proteins Article Measles virus Mice Prostate cancer Antigen Antigens Neoplasm Cell Line Tumor Pancreatic cancer Chlorocebus aethiops medicine Animals Humans Prodrugs Vero Cells Molecular Biology Oncolytic Virotherapy biology business.industry medicine.disease biology.organism_classification Combined Modality Therapy Xenograft Model Antitumor Assays Neoplasm Proteins Prostate Stem Cell Antigen Oncolytic virus Pancreatic Neoplasms Purine-Nucleoside Phosphorylase Immunology Cancer research Molecular Medicine Female CA19-9 business Vidarabine |
Zdroj: | Cancer Gene Therapy. 18:598-608 |
ISSN: | 1476-5500 0929-1903 |
Popis: | 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. |
Databáze: | OpenAIRE |
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