Determinants of combination GM-CSF immunotherapy and oncolytic virotherapy success identified through in silico treatment personalization

• DOI: 10.1371/journal.pcbi.1007495
• Publication Date: 2019-11-27T13:33:46Z
• Authors: Tyler Cassidy; Morgan Craig
• Keywords: Virotherapy; Combination therapy

Oncolytic virotherapies, including the modified herpes simplex virus talimogene laherparepvec (T-VEC), have shown great promise as potent instigators of anti-tumour immune effects. The OPTiM trial, in particular, demonstrated superior anti-cancer effects T-VEC compared to systemic immunotherapy treatment using exogenous administration granulocyte-macrophage colony-stimulating factor (GM-CSF). Theoretically, a combined approach leveraging cytokine and oncolytic virotherapy would elicit an even greater response improve patient outcomes. However, regimen scheduling combination immunostimulation therapy has yet be established. Here, we calibrate computational biology model sensitive resistant tumour cells interactions for implementation into silico clinical trial test individualize immuno- virotherapy. By personalizing optimizing immunostimulatory therapy, show improved simulated outcomes individuals with late-stage melanoma. More crucially, through evaluation individualized regimens, identified determinants GM-CSF that can translated clinically-actionable dosing strategies without further personalization. Our results serve proof-of-concept interdisciplinary approaches determining suggest promising avenues investigation towards tailored immunotherapy/oncolytic