Oncolytic Viral Kinetics Mechanistic Modeling of Talimogene Laherparepvec (IMLYGIC®) a First-in-Class Oncolytic Viral Therapy in patients with Advanced Melanoma.

Talimogene Laherparepvec (T-VEC) is a first in class oncolytic virotherapy approved for the treatment of unresectable melanoma recurrent after initial surgery. Biodistribution data from phase 2 study was used to develop a viral kinetics mechanistic model describing the interaction between cytokines like granulocyte-macrophage colony-stimulating factor (GM-CSF), immune system and T-VEC treatment. Our analysis found 1) viral infection rate has great influence on T-VEC treatment efficacy, 2) an increase of T-VEC dose of 10 2 pfu/mL 21 days and beyond after the initial dose of T-VEC resulted in a ~12% increase in response; and 3) at the systemic level the ratio of resting innate immune cells to the death rate of innate immune impact T-VEC treatment efficacy. This analysis clarifies under which condition the immune system either assists in eliminating tumor cells or inhibits T-VEC treatment efficacy which is critical to both efficiently design future oncolytic agents and understanding cancer development.