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Article

Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer

1
Department of Urology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1011, Switzerland
2
Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Academic Editor: M. Rita I. Young
Int. J. Mol. Sci. 2016, 17(7), 1125; https://doi.org/10.3390/ijms17071125
Received: 6 June 2016 / Revised: 30 June 2016 / Accepted: 5 July 2016 / Published: 14 July 2016
Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV) can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK) combined to Ganciclovir (GCV) led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC. View Full-Text
Keywords: human papillomavirus vectors; tumor-targeting; immunogenic suicide-gene therapy; bladder cancer human papillomavirus vectors; tumor-targeting; immunogenic suicide-gene therapy; bladder cancer
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MDPI and ACS Style

Hojeij, R.; Domingos-Pereira, S.; Nkosi, M.; Gharbi, D.; Derré, L.; Schiller, J.T.; Jichlinski, P.; Nardelli-Haefliger, D. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer. Int. J. Mol. Sci. 2016, 17, 1125. https://doi.org/10.3390/ijms17071125

AMA Style

Hojeij R, Domingos-Pereira S, Nkosi M, Gharbi D, Derré L, Schiller JT, Jichlinski P, Nardelli-Haefliger D. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer. International Journal of Molecular Sciences. 2016; 17(7):1125. https://doi.org/10.3390/ijms17071125

Chicago/Turabian Style

Hojeij, Rim, Sonia Domingos-Pereira, Marianne Nkosi, Dalila Gharbi, Laurent Derré, John T. Schiller, Patrice Jichlinski, and Denise Nardelli-Haefliger. 2016. "Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer" International Journal of Molecular Sciences 17, no. 7: 1125. https://doi.org/10.3390/ijms17071125

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