Transcriptome Changes in Glioma Cells upon Infection with the Oncolytic Virus VV-GMCSF-Lact
Oncolytic virotherapy is a rapidly evolving approach that aims to selectively kill cancer cells. We designed a promising recombinant vaccinia virus, VV-GMCSF-Lact, for the treatment of solid tumors, including glioma. In this viral construct, the viral thymidine kinase (tk) and growth factor (vgf) genes are replaced with human genes encoding GM-CSF and the apoptosis-inducing protein lactaptin, respectively. Lactaptin is a proteolytic fragment of human kappa-casein. It has proapoptotic activity against tumor cells, inducing apoptosis via the mitochondrial pathway and autophagy. We assessed how VV-GMCSF-Lact affects human cells using immortalized (U87 MG, U343 MG) and patient-derived glioma cultures (BR1, BR3, BR4, BR5), and non-malignant brain cell culture (NB). In this work, we studied changes in the transcriptome after infection with VV-GMCSF-Lact (at time points of 12 h or 24 h), for this we isolated RNA from these cells, built cDNA libraries and performed massively parallel sequencing on the NextSeq Illumina 1500 platform. Our findings highlight molecular markers, biological pathways, and gene networks influencing glioma cell sensitivity to VV-GMCSF-Lact and can be used to improve the effectiveness of cancer virotherapy.