The oncolytic adenovirus VCN-01 as therapeutic approach against pediatric osteosarcoma
Menée sur des lignées cellulaires et à l'aide de modèles murins d'ostéosarcome métastatique, cette étude met en évidence l'activité antitumorale d'un adénovirus oncolytique (VCN-01)
Purpose: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are one feasible option for osteosarcoma treatment. VCN-01 is a replication competent adenovirus specifically engineered to replicate in tumors with a defective RB pathway, presents an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase. The aim of this study is to elucidate whether the use of VCN-01 would be an effective therapeutic strategy for pediatric osteosarcoma. Experimental Design: We used osteosarcoma cell lines established from patients with metastatic disease (531MII, 678R, 588M, and 595M) and a commercial cell line (143B). MTT assays were carried out to evaluate the cytotoxicity of VCN-01. Hexon assays were used to evaluate the replication of the virus. Western blot analysis was performed to assess the expression levels of viral proteins and autophagic markers. The antitumor effect of VCN-01 was evaluated in an orthotopic and metastatic osteosarcoma murine animal models. Results: The current study found that VCN-01, a new generation genetically modified oncolytic adenovirus, administered locally or systemically, had a potent anti-sarcoma effect in vitro and in vivo in mouse models of intra-tibial and lung-metastatic osteosarcoma. Moreover, VCN-01 administration showed a safe toxicity profile. Conclusion: These results uncover VCN-01 as a promising strategy for osteosarcoma, setting the bases to propel a phase I/II trial for kids with this disease.