Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

The role of CCN1 in glioma virotherapy with oncolytic herpes simplex virus
Karly Jacobsen

Last modified: 2014-03-31


Oncolytic virotherapy is a tumor treatment that uses recombinant viruses capable of selectively targeting and destroying cancer cells.  Clinical trials have demonstrated varying degrees of success for the therapy with limitations predominantly due to barriers to viral spread throughout the tumor and the host immune response to the virus. Understanding changes in the tumor microenvironment during oncolytic virus (OV) infection is critical to designing successful therapeutic agents.  
Recent experimental studies have explored the efficacy of herpes simplex virus 1 (HSV-1) derived oncolytic viruses against glioma. These studies have demonstrated an upregulation of matricellular protein CCN1 following OV infection.  CCN1, also known as cysteine-rich angiogenic inducer 61, is a signaling protein that regulates a range of cellular activities and is known to be a powerful angiogenic inducer.  Overexpression of CCN1 in glioma cells following OV infection has been shown to induce activation of an antiviral defense response including the proinflammatory activation of macrophages.  In addition, CCN1 plays a role in initiating cross talk between the OV-infected glioma cells and macrophages.  The infiltration of macrophages increases viral clearance and, hence, limits the success of OV therapy.  Promisingly, neutralization of CCN1 in vivo has been shown to increase antitumor efficacy of OV therapy.  In this work we formulate and analyze a partial differential equations model with a moving boundary for the treatment of a glioma with an HSV-1 derived oncolytic virus. Our model demonstrates agreement with these experimental studies and tests hypotheses for the neutralization of CCN1, thus providing insights towards developing more effective OV therapy.


cancer therapy; glioma; oncolytic virus; partial differential equations