Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
AbstractBladder 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
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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.
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.Chicago/Turabian Style
Hojeij, Rim; Domingos-Pereira, Sonia; Nkosi, Marianne; Gharbi, Dalila; Derré, Laurent; Schiller, John T.; Jichlinski, Patrice; Nardelli-Haefliger, Denise. 2016. "Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer." Int. J. Mol. Sci. 17, no. 7: 1125.
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