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© Research
Publication : Science translational medicine

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Science translational medicine - 23 Jan 2019

Pascual-Pasto G, Bazan-Peregrino M, Olaciregui NG, Restrepo-Perdomo CA, 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 FL, Catalá-Mora J, Mora J, Alemany R, Cascalló M, Chantada GL, Carcaboso AM,

Link to Pubmed [PMID] – 30674657

Link to DOI – eaat932110.1126/scitranslmed.aat9321

Sci Transl Med 2019 Jan; 11(476):

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.

https://pubmed.ncbi.nlm.nih.gov/30674657