Effects of CCN1 and Macrophage Content on Glioma Virotherapy: A Mathematical Model

Bulletin of Mathematical Biology
Karly JacobsenAvner Friedman

Abstract

Oncolytic virus (OV) is a genetically engineered virus that can selectively replicate in and kill tumor cells while not harming normal cells. OV therapy has been explored as a treatment for numerous cancers including glioblastoma, an aggressive and devastating brain tumor. Experiments show that extracellular matrix protein CCN1 limits OV therapy of glioma by orchestrating an antiviral response and enhancing the proinflammatory activation and migration of macrophages. Neutralizing CCN1 by antibody has been demonstrated to improve OV spread and tends to increase the time to disease progression. In this paper, we develop a mathematical model to investigate the effects of CCN1 on the treatment of glioma with oncolytic herpes simplex virus. We show that numerical simulations of the model are in agreement with the experimental results and then use the model to explore the anti-tumor effects of combining antibodies with OV therapy. Model simulations suggest that the macrophage content of the tumor is a critical factor to the success of OV therapy and to the reduction in tumor volume gained with the CCN1 antibody.

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Citations

Jul 28, 2020·Cancers·Anna Maria MalfitanoGiuseppe Portella
May 26, 2017·Biomedicines·Nicholas L DentonTimothy P Cripe
Nov 24, 2016·Mathematical Biosciences and Engineering : MBE·Elzbieta RatajczykAvner Friedman
May 18, 2020·Mathematical Biosciences·Nourridine Siewe, Avner Friedman
May 20, 2021·Bulletin of Mathematical Biology·Noma Susan SenekalRachid Ouifki

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