The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene molecular profiles

Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal, however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). Therefore, we employ four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124 and the non-virulent Newcastle Disease Virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors and ependymomas) to determine their in vitro efficacy. These four OVs were screened on 14 patient-derived spheroids and the degree of oncolysis was assessed using an ATP-based assay. Subsequently, the observed viral efficacies were correlated to whole transcriptome data and Gene Ontology analysis was performed. Although no significant tumor type-specific OV efficacy was observed, whole transcriptome analysis revealed the intrinsic biological processes that associated with OV efficacy. The predictive power of those molecular profiles was further validated by screening the OV in vitro efficacy on additional PBTs. In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique molecular profiles. Those profiles highlight the cellular intrinsic factors for potent oncolysis, that could potentially allow stratification of patients and lead to improved OV responses.