Optimal Individualized Combination Immunotherapy/Oncolytic Virotherapy Determined Through In Silico Clinical Trials Improves Late Stage Melanoma Patient Outcomes

Oncolytic virothcrapics, 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 the superior anti-cancer effects of T-VEC as compared to more traditional immunotherapy treatment using exogenous administration of granulocyte-macrophage colony-stimulating factor (GM-CSF). Theoretically, a combined approach leveraging immunotherapies: like exogenous cytokine administration and oncolytic virotherapv would elicit an even greater immune response and improve patient outcomes, but given that their efficacy and safety must be tested in large clinical trials, combination therapeutic regimens have yet to be established. By adopting computational biology and in silico clinical trial approaches, here we show significantly improved patient outcomes for individuals with late-stage melanoma by personalizing and optimizing combination oncolytic, virotherapv and GM-CSF therapy. Our results serve as a proof-of-concept, for interdisciplinary approaches to determining combination therapy, and suggest promising avenues of investigation towards tailored combination immunotherapy/oncolytic virotherapy.