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

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 afte...

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Autores principales: Hojeij, Rim, Domingos-Pereira, Sonia, Nkosi, Marianne, Gharbi, Dalila, Derré, Laurent, Schiller, John T., Jichlinski, Patrice, Nardelli-Haefliger, Denise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964499/
https://www.ncbi.nlm.nih.gov/pubmed/27428950
http://dx.doi.org/10.3390/ijms17071125
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author Hojeij, Rim
Domingos-Pereira, Sonia
Nkosi, Marianne
Gharbi, Dalila
Derré, Laurent
Schiller, John T.
Jichlinski, Patrice
Nardelli-Haefliger, Denise
author_facet Hojeij, Rim
Domingos-Pereira, Sonia
Nkosi, Marianne
Gharbi, Dalila
Derré, Laurent
Schiller, John T.
Jichlinski, Patrice
Nardelli-Haefliger, Denise
author_sort Hojeij, Rim
collection PubMed
description 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.
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spelling pubmed-49644992016-08-03 Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer Hojeij, Rim Domingos-Pereira, Sonia Nkosi, Marianne Gharbi, Dalila Derré, Laurent Schiller, John T. Jichlinski, Patrice Nardelli-Haefliger, Denise Int J Mol Sci Article 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. MDPI 2016-07-14 /pmc/articles/PMC4964499/ /pubmed/27428950 http://dx.doi.org/10.3390/ijms17071125 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hojeij, Rim
Domingos-Pereira, Sonia
Nkosi, Marianne
Gharbi, Dalila
Derré, Laurent
Schiller, John T.
Jichlinski, Patrice
Nardelli-Haefliger, Denise
Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
title Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
title_full Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
title_fullStr Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
title_full_unstemmed Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
title_short Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer
title_sort immunogenic human papillomavirus pseudovirus-mediated suicide-gene therapy for bladder cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964499/
https://www.ncbi.nlm.nih.gov/pubmed/27428950
http://dx.doi.org/10.3390/ijms17071125
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