Toxicity and Biodistribution of the Oncolytic Virus VCN-01 Following Intracranial Injection in Syrian Hamsters.
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Among solid pediatric tumors, brain tumors are the leading cause of cancer-related mortality. While survival rates have improved for certain pediatric brain tumor subtypes, the overall prognosis remains poor. Consequently, there is an urgent need for novel therapies that are not only effective but also less toxic. Oncolytic viruses have emerged as promising therapeutic agents due to their ability to selectively replicate in tumor cells while sparing healthy tissue and their potential to induce systemic antitumor immune responses. VCN-01 is a replication-competent oncolytic adenovirus whose efficacy has been demonstrated in clinical trials after systemic administration in combination with chemotherapy. Evidence of antitumor activity has also been obtained after intracranial administration in preclinical models of various brain tumors, including high-grade gliomas. However, before progressing to clinical trials for those indications, it is essential to assess the safety of its intracranial administration. In this study, we evaluated the toxicity and biodistribution of VCN-01 following intracranial injection in a Syrian hamster model. Two viral doses were tested: 1.5 × 109 and 1.5 × 1010 viral particles (vp)/animal, corresponding to 5 and 50 times the starting clinical dose (1010 vp/patient), respectively. Our toxicity analysis revealed a favorable safety profile, with no adverse effects observed following administration. Biodistribution studies demonstrated that VCN-01 primarily remained confined to the brain, with only minimal presence detected in peripheral tissues. The neutralizing antibody response against the virus was stronger in females than in males, correlating with a lower detection of vp in females compared with males. In conclusion, these findings support the safety of intracranial administration of VCN-01 and provide a strong rationale for its further development as a therapeutic option for patients with brain tumors.