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Int. J. Mol. Sci. 2016, 17(7), 1125; doi:10.3390/ijms17071125

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
Received: 6 June 2016 / Revised: 30 June 2016 / Accepted: 5 July 2016 / Published: 14 July 2016
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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