Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01.

Détails

ID Serval
serval:BIB_932ED13BAA1C
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01.
Périodique
Science translational medicine
Auteur(s)
Pascual-Pasto G., Bazan-Peregrino M., Olaciregui N.G., Restrepo-Perdomo C.A., Mato-Berciano A., Ottaviani D., Weber K., Correa G., Paco S., Vila-Ubach M., Cuadrado-Vilanova M., Castillo-Ecija H., Botteri G., Garcia-Gerique L., Moreno-Gilabert H., Gimenez-Alejandre M., Alonso-Lopez P., Farrera-Sal M., Torres-Manjon S., Ramos-Lozano D., Moreno R., Aerts I., Doz F., Cassoux N., Chapeaublanc E., Torrebadell M., Roldan M., König A., Suñol M., Claverol J., Lavarino C., Carmen de T., Fu L., Radvanyi F., Munier F.L., Catalá-Mora J., Mora J., Alemany R., Cascalló M., Chantada G.L., Carcaboso A.M.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Statut éditorial
Publié
Date de publication
23/01/2019
Peer-reviewed
Oui
Volume
11
Numéro
476
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1 VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.
Pubmed
Web of science
Création de la notice
05/02/2019 14:52
Dernière modification de la notice
20/08/2019 14:56
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