Presentation (CTI)

OBJECTIVES: Retinoblastoma is a primarily paediatric, rare, intraocular cancer caused by mutations in the RB1 gene which can lead to mild-to-severe vision loss. Pre-clinical and early-phase clinical studies have investigated the viability of oncolytic viruses and gene therapies in targeting the RB1 gene pathway, but there is uncertainty surrounding their efficacy and safety. This review aimed to comprehensively identify and describe published data from clinical trials of oncolytic viruses and gene therapies in children with retinoblastoma.
METHODS: A systematic search of literature published up to 07 January 2026 in Embase, MEDLINE, the Cochrane Library, clinical trial registries, and key conference proceedings to identify clinical trials of oncolytic viruses and gene therapies in children with retinoblastoma, was undertaken. Two reviewers independently screened the literature, extracted data, and assessed methodological quality using the Cochrane ROBINS-I tool. Retrieved data included study details, baseline characteristics, and efficacy and safety outcomes (PROSPERO registration: CRD420251064061).
RESULTS: Of 117 articles identified, 8 reporting on 2 serious risk of bias Phase I clinical trials in refractory childhood retinoblastoma were selected for inclusion. In one study, targeted vitreous seeds were resolved in all 8 children treated intravitreally with adenoviral vectors containing a herpes thymidine kinase gene followed by intravenous ganciclovir. Toxicities such as inflammation, corneal oedema, and increased intraocular pressure were observed, and all patients were eventually enucleated. A second study reported partial responses in 5/9 children with retinoblastoma treated with the oncolytic adenovirus VCN-01. Adverse events occurred in 7 patients. 6 children were enucleated, and vision was preserved in 3 eyes at follow-up.
CONCLUSIONS: Although oncolytic viruses and gene therapies are regarded as experimental in children with retinoblastoma, early clinical trials have demonstrated their potential efficacy and safety for intraocular use. Larger, long-term controlled studies are needed to further validate Phase I results.