An engineered oncolytic adenovirus showed an antisarcoma effect both in vitro and in vivo in mouse models, according to a recent report. Oncolytic adenoviruses are specifically engineered to destroy cancer cells, and these are thought to be a feasible treatment for osteosarcoma.
Osteosarcoma is the most common malignant bone tumor in children and adolescents, the study authors wrote. Despite treatment with aggressive chemotherapy, more than a third of patients don’t respond or can develop bone or lung metastasis.
Investigators from The Health Research Institute of Navarra in Pamplona, Spain tested the efficacy of VCN-01, a replication-competent adenovirus. VCN-01 was engineered to replicate tumors with a defective RB pathway, they explained, which presented an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase.
Using osteosarcoma cell line established from patients with metastatic disease, as well as a commercial cell line, the investigators used assays to evaluate the cytotoxicity of VCN-01 while other assays were used to monitor the replication of the virus. The investigators used orthotopic and metastatic osteosarcoma murine animal models to evaluate the antitumor effect of VCN-01.
In the pediatric osteosarcoma-derived cell lines the investigators used in their testing, VCN-01 replicated in vitro showed a “robust” oncolytic effect. In further analysis, the investigators learned that about 70% of control mice presented lung metastases derived from the primary osteosarcoma tumor when treated with VCN-01 injection at days 7 and 21 administered at 2 differing dosages.
The investigators also monitored weight of the mice, controlling weight every week after local (intratumoral) or systemic (tail vein) viral administration. Mice did not lose weight with VCN-01 administration, the study authors wrote, adding that route of administration did not affect weight loss. Viral concentration did not affect weight loss either.
In addition, locally or systemically administered VCN-01 was not significantly toxic and was well tolerated.
The investigators monitored the antitumor effect of VCN-01 in an orthotopic osteosarcoma model in 3 groups of mice. They were monitored weekly for 90 days. Tumor volumes were significantly bigger in the control group relative to the treatment group. All control mice displayed visible tibial tumors, compared to 3 out of 10 tibias in the group treated with some VCN-01 and 0 in the group treated with a higher dose of VCN-01.
From this experiment, the investigators found that about 70% of the control mice presented lung metastases derived from the primary sarcoma tumor. The low-dose VCN-01 group showed just 1 mouse that developed lung metastasis.
The study authors said that prior literature has demonstrated that oncolytic adenoviruses present a potential therapeutic approach for pediatric osteosarcoma, but with the new research, they said “VCN-01, a new generation of genetically modified oncolytic adenovirus, administered locally or systemically, had a potent antisarcoma effect in vitro and in vivo in mouse models of intratibial and lung metastatic osteosarcoma.”
They determined that VCN-01 was safe in terms of toxicity, and they said their findings “consolidate the case for pushing VCN-01 as a realistic therapeutic option for kids with osteosarcoma.”
The paper, titled “The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma
,” was published in the journal Clinical Cancer Research.