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

Détails

Ressource 1Télécharger: BIB_43FA35E9A155.P001.pdf (2231.85 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_43FA35E9A155
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer.
Périodique
International journal of molecular sciences
Auteur(s)
Hojeij R., Domingos-Pereira S., Nkosi M., Gharbi D., Derré L., Schiller J.T., Jichlinski P., Nardelli-Haefliger D.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Statut éditorial
Publié
Date de publication
14/03/2016
Peer-reviewed
Oui
Volume
17
Numéro
7
Pages
E1125
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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.

Mots-clé
Animals, Antiviral Agents/therapeutic use, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Combined Modality Therapy, Female, Ganciclovir/therapeutic use, Genetic Therapy, Genetic Vectors, Humans, Mice, Mice, Inbred C57BL, Papillomaviridae/enzymology, Papillomaviridae/genetics, Papillomaviridae/immunology, Thymidine Kinase/genetics, Thymidine Kinase/metabolism, Urinary Bladder Neoplasms/enzymology, Urinary Bladder Neoplasms/genetics, Urinary Bladder Neoplasms/immunology, Urinary Bladder Neoplasms/therapy
Pubmed
Open Access
Oui
Création de la notice
24/07/2016 15:55
Dernière modification de la notice
20/08/2019 14:48
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