A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer
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Bertrand Neveu1,*, Pallavi Jain1,*, Bernard Têtu2, Lily Wu3,4, Yves Fradet1 and Frédéric Pouliot1
1 Département de Chirurgie, Faculté de Médecine, Université Laval, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Canada
2 Département de Biochimie et Pathologie, Faculté de Médecine, Université Laval, Centre Hospitalier Universitaire de Québec, Québec, Canada
3 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
4 Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
* These authors have contributed equally to this work
Frederic Pouliot , email:
Keywords: prostate cancer, PCA3, vector system and targeting strategies, non-invasive imaging in animal
Received: July 15, 2015 Accepted: November 15, 2015 Published: November 22, 2015
Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and cloned into type 5 adenovirus. PCA3-3STA activity was highly specific for PCa cells, ranging between 98.7- and 108.0-fold higher than that for benign primary prostate epithelial or non-PCa cells, respectively. In human PCa xenografts, PCA3-3STA displayed robust bioluminescent signals at levels that are sufficient to translate to positron emission tomography (PET)-based reporter imaging. Remarkably, when freshly isolated benign or cancerous prostate biopsies were infected with PCA3-3STA, the optical signal produced from primary PCa biopsies was significantly higher than from benign prostate biopsies (4.4-fold, p < 0.0001). PCA3-3STA therefore represents a PCa-specific expression system with the potential to target, with high accuracy, primary or metastatic PCa epithelial cells for imaging, vaccines, or gene therapy.
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