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QUANTITATIVE IMPACT OF IMMUNOMODULATION VERSUS ONCOLYSIS WITH CYTOKINE-EXPRESSING VIRUS THERAPEUTICS

Title
QUANTITATIVE IMPACT OF IMMUNOMODULATION VERSUS ONCOLYSIS WITH CYTOKINE-EXPRESSING VIRUS THERAPEUTICS
Author
윤채옥
Keywords
Oncolytic virotherapy; adenovirus; cytokines; co-stimulatory molecules; mathematical model; ordinary differential equations model
Issue Date
2015-08
Publisher
AMER INST MATHEMATICAL SCIENCES
Citation
MATHEMATICAL BIOSCIENCES AND ENGINEERING, v. 12, no. 4, Page. 841-858
Abstract
The past century's description of oncolytic virotherapy as a cancer treatment involving specially-engineered viruses that exploit immune deficiencies to selectively lyse cancer cells is no longer adequate. Some of the most promising therapeutic candidates are now being engineered to produce immunostimulatory factors, such as cytokines and co-stimulatory molecules, which, in addition to viral oncolysis, initiate a cytotoxic immune attack against the tumor. This study addresses the combined effects of viral oncolysis and T-cell-mediated oncolysis. We employ a mathematical model of virotherapy that induces release of cytokine IL-12 and co-stimulatory molecule 4-1BB ligand. We found that the model closely matches previously published data, and while viral oncolysis is fundamental in reducing tumor burden, increased stimulation of cytotoxic T cells leads to a short-term reduction in tumor size, but a faster relapse. In addition, we found that combinations of specialist viruses that express either IL-12 or 4-1BBL might initially act more potently against tumors than a generalist virus that simultaneously expresses both, but the advantage is likely not large enough to replace treatment using the generalist virus. Finally, according to our model and its current assumptions, virotherapy appears to be optimizable through targeted design and treatment combinations to substantially improve therapeutic outcomes.
URI
http://www.aimsciences.org/journals/displayArticlesnew.jsp?paperID=11018http://hdl.handle.net/20.500.11754/27164
ISSN
1547-1063; 1551-0018
DOI
10.3934/mbe.2015.12.841
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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