Mathematical model for radial expansion and conflation of intratumoral infectious centers during curative oncolytic virotherapy

• Published in: Molecular therapy Vol. 20; no. 9; p. 53
• Main Authors: Bailey, Kent, Naik, Shruthi, Steele, Michael, Pham, Linh, Hadac, Elizabeth, Nace, Rebecca, Greiner, Suzanne, Peng, Kah Whye, Russell, Stephen J
• Format: Journal Article
• Language: English
• Published: 01.09.2012
• Subjects: Vesicular stomatitis virus
• ISSN: 1525-0016; 1525-0024

Oncolytic viruses destroy tumors by diverse mechanisms and with different kinetics. Previous (dynamic, non-spatial) mathematical models developed to guide protocol design and predict outcomes have been theoretical and complex. Here, we developed a simple spatial mathematical model of oncolytic virotherapy induced from detailed immunohistochemical analyses of plasmacytomas regressing after a single intravenous injection of an oncolytic vesicular stomatitis virus (VSV). Intratumoral virus spread dramatically outstripped tumor growth during the first 48 hours after virus administration, but was then rapidly curtailed by host antiviral defenses (these were syngeneic tumors in fully immunocompetent mice). The new model calculates the probability of any tumor cell surviving after intravenous VSV administration based on three key parameters; the size of the tumor, the density of initially infected cells in the tumor, and the average maximum size attained by the infectious centers. Predicted effects of virus dose modification, antiviral immune response modulation and tumor size were investigated through additional in vivo experimentation and the results are in good agreement with the predictions of the model. This simple, convenient and well-validated new spatial model gives helpful insights into the process of oncolytic virotherapy will be useful to guide the further optimization of the approach.